TECHNICAL FIELD

[0001] The present invention relates to biocompatible polymer compositions for use in biomedical applications.

BACKGROUND ART

[0002] The following discussion of the background art is intended to facilitate an understanding of the present invention only. The discussion is not an acknowledgement or admission that any of the material referred to is or was part of the common general knowledge as at the priority date of the application.

[0003] The nature and chemistry of synthetic polymers used in biomedical applications varies depending on the application. In general, they need to satisfy the requirement of being able to be fabricated into any shape, and the ability to be adapted as far as their mechanical properties are concerned to the application at hand. Such polymers can also be tailored to contain various functionalities allowing them to integrate into the environment in which they are to be placed. Some implantable polymers for example are biodegradable and can be easily resorbed through metabolic pathways that the body uses to cleanse itself of undesired by-products.

[0004] Biodegradable polymers are particularly useful in the development of therapeutic devices, including temporary implants and three-dimensional scaffolds for tissue engineering. The use of biodegradable polymeric materials for pharmacological applications including delivery vehicles for controlled and/or sustained drug release is also a common application. However, these applications require strict control of physicochemical, biological, and degradation properties of the polymers in order to be employed effectively.

[0005] A number of biodegradable polymers have been developed that break down in vivo into their respective monomers within weeks or a few months. Despite the availability of these synthetic degradable polymers, there is still a need to develop degradable polymers which can further extend the useful range of available properties, particularly while maintaining desirable mechanical properties.

[0006] Many of the biodegradable polymers previously studied belong to the polyester family. Among these poly(a-hydroxy acids) such as poly(glycolic acid), poly(lactic acid) and a range of their copolymers have comprised the bulk of published material on biodegradable polyesters and have a long history of use as synthetic biodegradable materials in a number of clinical applications. Among these applications, poly(glycolic acid), poly(lactic acid) and their copolymers, poly(p-dioxanone), and copolymers of trimethylene carbonate and glycolide have been widely used. Their major applications include resorbable sutures, drug delivery systems and orthopaedic fixation devices such as pins, rods and screws. Among the families of synthetic polymers, the polyesters have been attractive for use in these applications because of their ease of degradation by hydrolysis of their ester linkage, the fact that their degradation products are resorbed through metabolic pathways in some cases and their potential to be tailored in terms of their structure to alter degradation rates.

[0007] To-date, biodegradable synthetic polymers used as scaffolds in tissue engineering are often severely limited in application because of the lack of strength and durability. A frequent problem with biodegradable polymers is that they degrade faster than the surrounding cells can synthesize a replacement matrix, resulting in mechanical failure.

[0008] It is also a requirement in many applications that an implanted medical device should degrade after its primary function has been met. Some biodegradable polymers have shown very long in vivo degradation periods, up to greater than one year. This very long degradation time is, in many applications, undesirable as the persistence of a polymer at a wound healing site may lead to a chronic inflammatory response in the patient. Slowly degrading poly(hydroxybutyrate) patches used to regenerate arterial tissue have been found to elicit a long term (greater than two years) macrophage response ¹ . Macrophages were identified as being involved in the degradation of the poly(hydroxybutyrate) implants and this long-term macrophage response appears to indicate the presence of persistent, slowly degrading particulate material originating from the implant.

[0009] It is also a requirement in many medical applications that biocompatible polymers are suitably permeable, and in some cases suitably porous, especially in tissue regeneration, wound healing and drug delivery applications.

[0010] Materials which can be utilized in transplant as scaffolds and that already contain the desired combination of strength, flexibility, permeability, porosity, processability and in-vivo degradation rate would be a significant improvement over scaffold materials currently available. Tissue materials that are strong, durable, permeable and flexible would greatly enable the use of tissue engineering principles and concepts to create a potentially vast range of commercial products and therapies.

[0011] Such materials would find useful applications in the manufacture of sutures, suture fasteners, meniscus repair devices, rivets, tacks, staples, screws (including interference screws), bone plates and bone plating systems, surgical mesh, repair patches, slings, cardiovascular patches, orthopaedic pins (including bone filling augmentation material), heart valves and vascular grafts, adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, bone marrow scaffolds, meniscus regeneration devices, ligament and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostats, as well as for use in existing medical applications, including drug delivery and controlled release of drugs and other bioactive materials.

[0012] Such compositions would also be useful to make or form coatings on a wide variety of devices, including stents, catheters, and sensors. The advantages of such biocompatible polymer compositions in new and existing applications include the use of a biodegradable substitute material in the application, or the addition of some other desirable characteristic or attribute associated with the application or use, such as a mechanical or surface property, physical or chemical property, sterilization technique, biocompatibility, degradation mechanism, packaging preference, and/or an improvement in stability.

[0013] Finding the right balance in properties of thermoplastic alpha-polyesters for biomedical applications such as those listed above is challenging. Alpha-polyesters (Aliphatic polyesters) such as poly(p-dioxanone) (PDO), polylactic acid (PLA), poly(s-caprolactone) (PCL) and polyglycolic acid (PGA) are typically limited by either mechanical performance or degradation rate. For instance, PDO shows good mechanical flexibility, biodegradability and biocompatibility, however, its rapid degradation rate limits its applications.

[0014] Alpha polyesters have attracted great interest from researchers and medical industries in the last two decades because of their outstanding mechanical properties, biodegradability and biocompatibility. The most widely used alpha polyesters are polylactic acid (PLA), poly(s- caprolactone) (PCL), polyethylene oxide) (PEO), polyglycolic acid (PGA) and poly(p- dioxanone) (PPDO, also known as PDO, PDS or PDX), with the most common applications found in biodegradable products, especially surgical devices such as surgical sutures, stents, anchors, clips, screws, plates and bone fixation devices ² .

[0015] Although all aliphatic polyesters show good biocompatibility and biodegradability, the properties of each polymer, such as degradation rate, mechanical and thermal properties, and crystallinity change with small differences in chemical structure ² . Several copolymers, such as poly(lactide-co-glycolide) (PLA-co-PGA or PLGA) and poly(lactide-co-caprolactone) (PLA-co- PCL, PLCL or LCL), have been commercially developed to provide balanced properties between alpha-polyesters. Blending polymers together is a viable approach to engineer new materials. Being biodegradable and biocompatible, PLA is a thermoplastic with good mechanical properties. However, substantial efforts have been made to alter the PLA’s properties via blending it with hydrophilic polymers, such as PCL. Being a ductile biodegradable polymer, PCL has been employed to modify the PLA behaviour from rigid to ductile since the former has been chosen as a blending partner for the latter ^3-5 . Though these two polymers are immiscible over a wide range of temperature, composition and molecular weight, as confirmed by previous studies ⁶ , the copolymer of PLA and PCL shows better miscibility and averaged properties compared to blends. However, the degradation time of the PLA/PCL blends and PLCL copolymers is still high for many applications such as soft tissue engineering and wound dressing.

[0016] PDO is a biodegradable polyester used in medical devices, tissue engineering scaffolds and controlled drug delivery due to its excellent biocompatibility, biodegradability, and mechanical flexibility ^7-9 . But PDO has a high degradation rate limiting its use in many applications ¹⁰ . PDO-based blends/copolymers have been widely investigated during the last two decades in order to obtain biopolymers with new degradation characteristics, along with new physical, mechanical and thermal properties. For instance, Poly(p-dioxanone)/poly(ethylene glycol) (PDO/PEG) films were prepared by UV crosslinking acrylated PDO with PEG diacrylate. It was shown that the degree of crystallinity of the films decreased with increasing content of PEG, while the thermal stability of the films increased ¹¹ .

[0017] Other polymers such as elastin, gelatin, and poly(vinyl alcohol) (PVA) have been also blended with PDO to increase the hydrophilicity and biocompatibility of scaffolds for tissue engineering purposes ^{12 13} . Pezzin et al. ¹⁴ investigated the thermal, mechanical and morphological properties of PDO/PLLA blends prepared by solvent casting method. They observed that 20 wt% of PDO can act as a plasticizer in the blend, enabling a more flexible material with a higher elongation at failure and neck formation. They also showed that PDO/PLLA blends degrade faster than PLLA but slower than PDO, highlighting the dependency on the proportion of each polymer in the blend ¹⁵ .

[0018] Poly(para-dioxanone-co-L-lactide) (PDOLLA) was employed as a compatibilizer in blends of poly(L-lactide)/poly(para-dioxanone) (PLLA/PDO) to moderate the immiscibility between PDO and PLLA phases ¹⁶ . By adding 1-3 wt% PDOLLA, the weight loss of PLLA/PPDO (85/15 w/w) increased by approximately 16% after 8 weeks of hydrolytic degradation, while the tensile strength of the blend improved by 20% during the same degradation time. Hybrid scaffolds composed of PCL and PDO have also been fabricated, via either blending or co electrospinning, to overcome the long degradation rate of PCL ¹⁷ . Goonoo et al. ⁸ improved the cell biomimetic mineralization and multicellular response of electrospun PDO-based mats for skeletal tissue regeneration through blending PDO with (i) poly(hydroxybutyrate-co-valerate) (PHBV) in the presence of hydroxyapatite (HA) and (ii) aloe vera (A V). PDO/AV electrospun scaffolds showed better in-vivo biocompatibility than PDO/PHBV/HA scaffolds due to the reduced fibrous capsule thickness and improved blood vessel generation.

[0019] Despite these extensive efforts, there is a need to develop alternative biocompatible polymer compositions wherein the degradation time of the polymer composition coincides with the regeneration and/or healing process in such a way as to ensure proper remodelling of the tissue.

[0020] There is also a need to develop alternative biocompatible polymer compositions capable of maintaining suitable permeability and processability for their intended applications.

[0021] There is also a need to develop alternative biocompatible polymer compositions having permeability and or degradation properties that are compatible with controlled and/or sustained drug release applications.

[0022] There is also a need to develop alternative biocompatible polymer compositions wherein the mechanical properties of the biomaterial are sufficient to promote regeneration during a patient’s everyday activities, and wherein changes in the mechanical properties due to degradation maintain compatibility with the healing or regeneration process

[0023] It is against this background that the present invention has been developed.

SUMMARY OF THE INVENTION

[0024] In one embodiment, the invention described herein provides a biocompatible polymer composition, wherein the polymer composition is biodegradable and wherein the polymer composition comprises, PDO and LCL.

[0025] In one embodiment, the invention described herein provides a biocompatible polymer composition, wherein the polymer composition is biodegradable, wherein the polymer composition comprises, PDO and LCL, and wherein the PDO is dispersed as droplets within an LCL matrix.

[0026] In some embodiments, the invention described herein provides nanocomposite or composite materials comprising a biocompatible polymer composition, wherein the polymer composition is biodegradable, wherein the polymer composition comprises, PDO and LCL, and wherein the PDO is dispersed as droplets within an LCL matrix. [0027] In some embodiments, the polymer compositions, nanocomposites and composite materials of the invention provide surprising and unexpected mechanical and/or degradation properties making them particularly suitable for a range of medical applications.

BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Further features of the present invention are more fully described in the following description of several non-limiting embodiments thereof. This description is included solely for the purposes of exemplifying the present invention. It should not be understood as a restriction on the broad summary, disclosure or description of the invention as set out above. The description will be made with reference to the accompanying drawings in which:

Figure 1 are FTIR spectra of LCL/PDO binary blends in (A) 500-4000 crrr ¹ and (B) 1000-1800 cnr ¹ wave numbers.

Figure 2 are (A) DSC diagrams of LCL/PDO binary blends and (B) plots of the effect of PDO proportion in the blend on the degree of crystallinity (X _c ) and melting temperature (T _m ) in blends.

Figure 3.1 is a series of SEM images of the PDO/LCL blends. (A) surface of LCL; (B) surface of PDO; (C) surface of PD03LCL7; (D) cross-section of PD03LCL7; (E) surface of PD05LCL5; (F) cross-section of PD05LCL5; (G) surface of PD07LCL3; (H) cross-section of PD07LCL3. The pattern picture in Figure B was reproduced with permission from the authors of ³⁰ .

Figure 3.2 is a series of SEM images of the PDO/LCL blends. (A) cross-section of PD03.5LCL6.5; (B) cross-section of PD02.5LCL7.5; (C) cross-section of PD02LCL8; (D) cross-section of PD01 LCL9; (E) cross-section of PDO0.5LCL9.5.

Figure 4 is a plot of tensile stress-strain curves of LCL/PDO binary blends. The expanded inset shows the traces for PD05LCL5 and PD07LCL3 only.

Figure 5 is a series of plots of weight loss percentage (A, B) and pH change (C, D) of PDO/LCL blends during normal (A, C) and accelerated (B, D) degradation.

Figure 6 is a series of FTIR spectra of PDO/LCL blends during accelerated and normal degradation time. Figure 7 are the FTIR-ATR spectra of LCL/PDO binary blends during normal (A) and accelerated (B) degradation.

Figure 8 is a series of DSC curves of PDO/LCL blends during accelerated and normal degradation time.

Figure 9 is a plot of the effect of hydrolytic degradation on crystallinity (X _c ) of neat PDO, neat LCL and binary blends in normal (A) and accelerated (B) degradation.

Figure 10 is a series of images depicting; (A-O) Surface morphology of PDO/LCL blends in week 4, 8, and 16 of normal degradation. (P) and (Q) show the cross- section of PD03LCL7 in week 16 and day 12, respectively. Arrows indicate examples of crack formation.

Figure 11 is a series of plots of the effect of hydrolytic degradation on tensile properties of blends in normal (A, B) and accelerated (C, D) degradation conditions.

Figure 12 is a series of stress-strain curves of PDO/LCL blends during accelerated and normal degradation time.

Figure 13 shows (A) the quantitative results of fibroblast cell proliferation by MTS test; and (B-F) a series of fluorescence microscopy images of attached fibroblasts on the surface of PDO (B), PD07LCL3 (C), PD05LCL5 (D), PD03LCL7 (E), and LCL (F) after 3 days culture. The average results of 3 tests (n=3) were reported for MTS proliferation. Scale bar is 100 pm.

Figure 14 is an SEM image of the cross-section morphology of a PDO/LCL/Hydroxyapatite nanocomposite PDO2LCL8-10nHA.

Figure 15 are SEM images of the cross-section morphology of PDO/LCL/Silk composites PD02LCL8-5S (A) and PD02LCL8-15S (B); encircled regions show agglomerated silk content.

Figure 16 is a plot of Differntial Scanning Calorimetry (DSC) traces for PDO/LCL/Silk composites PD02LCL8-5S, PDO2LCL8-10S, and PD02LCL8-15S compared to a corresponding polymer composition without silk PD02LCL8. DEFINITIONS

[0029] Throughout this specification, unless the context requires otherwise, the word "comprise" or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.

[0030] As used herein, the term “PLLA” refers to a poly(lactide) polymer. The skilled addressee will be aware that PLLA is referred to by other names in the art, including “polylactic acid”.

[0031] As used herein, the term “PCL” refers to a poly(caprolactone) polymer.

[0032] As used herein, the term “LCL” refers to a poly(lactide-co-caprolactone) copolymer, and includes linear copolymers, branched copolymers, grafted copolymers, star-shaped copolymers, dendronized or other architecture copolymers, alternating, random or statistical, or block copolymers of lactide and caprolactone monomers. The skilled addressee will be aware that LCL is referred to by other names in the art, including “PLCL”.

[0033] As used herein, the term “PDO” refers to a poly(p-dioxanone) polymer. The skilled addressee will be aware that PDO is referred to by other names in the art, including “PPDO”, “PDS” and “PDX”.

[0034] As used herein, the term “biodegradable” refers to the degradation of polymer compositions with time, when immersed in buffered aqueous solutions at physiological pH.

[0035] As used herein, the term “dynamic porosity” refers to the property possessed by compositions of the present invention, wherein changes in the degree of porosity of the compositions occur with time, when immersed in buffered aqueous solutions at physiological pH.

[0036] As used herein, the term “biomedical application” refers, without limitation, to an application in the manufacture of sutures, suture fasteners, meniscus repair devices, rivets, tacks, staples, screws (including interference screws), bone plates and bone plating systems, surgical mesh, repair patches, slings, cardiovascular patches, orthopaedic pins (including bone filling augmentation material), heart valves and vascular grafts, adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, bone marrow scaffolds, meniscus regeneration devices, ligament and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostats, as well as application in existing medical contexts, including drug delivery and controlled release of drugs and other bioactive materials, forming coatings on a wide variety of implantable devices, including stents, catheters, and sensors, the use of a biodegradable substitute material in the application, or the addition of some other desirable characteristic or attribute associated with the application or use, such as a mechanical or surface property, physical or chemical property, sterilization technique, biocompatibility, degradation mechanism, packaging preference, and/or an improvement in stability.

[0037] As used herein, the term “active agent” refers to a compound or composition that has a particular desired activity. For example, an active agent can be a therapeutic compound. Alternatively an “active agent” can include a compound or composition capable of improving the physical or mechanical properties of the biocompatible polymer composition of the invention and/or the biocompatibility of the polymer composition of the invention in the context or particular application in which the composition is to be employed. Without limitations the active agent can be selected from the group consisting of small organic or inorganic molecules, saccharines, oligosaccharides, polysaccharides, peptides, proteins, silk fibroin, peptide analogs and derivatives, peptidomimetics, nucleic acids, nucleic acid analogs and derivatives, antibodies, antigen binding fragments of antibodies, lipids, extracts made from biological materials, naturally occurring or synthetic compositions, biologies, biosimilars and any combinations thereof.

[0038] The term “active agent” may mean one active agent, or may encompass two or more active agents.

[0039] Active agents may include, without limitation, anti-microbial agents; anti-inflammatory agents; stem cells; transcription factors; antiproliferative agents; anticancer agents; growth factors; hormones; steroids; enzyme or receptor modulators; hydroxyapatite; tricalcium phosphate; polyhedral oligomeric silsesquioxane (POSS); POSS derivatives; pyrithione salts; ketoconazole; salicylic acid; curcumin or a derivative of curcumin, curcuminoids; tetrahydro curcuminoids; titanium dioxide (TiCk); zinc oxide (ZnO); chloroxylenol; flavanoids; CoQIO; vitamin C; herbal extracts; alkaloids; 13-cis retinoic acid; 3,4-methylenedioxymethamphetamine; 5-fluorouracil; 6,8-dimercaptooctanoic acid (dihydrolipoic acid); abacavir; acebutolol; acetaminophen; acetaminosalol; acetazolamide; acetohydroxamic acid; acetylsalicylic acid; acitretin; aclovate; acrivastine; actiq; acyclovir; adapalene; adefovir dipivoxil; adenosine; Albaconazole; albuterol; alfuzosin; Allicin; allopurinol; alloxanthine; allylamines; almotriptan; alpha-hydroxy acids; alprazolam; alprenolol; aluminum acetate; aluminum chloride; aluminum chlorohydroxide; aluminum hydroxide; amantadine; amiloride; aminacrine; aminobenzoic acid (PABA); aminocaproic acid; aminoglycosides such as streptomycin, neomycin, kanamycin, paromycin, gentamicin, tobramycin, amikacin, netilmicin, spectinomycin, sisomicin, dibekalin and isepamicin; aminosalicylic acid; amiodarone; amitriptyline; amlodipine; amocarzine; amodiaquin; Amorolfin; amoxapine; amphetamine; amphotericin B; ampicillin; anagrelide; anastrozole; Anidulafungin; anthralin; antibacterial sulfonamides and antibacterial sulphanilamides, including para-aminobenzoic acid, sulfadiazine, sulfisoxazole, sulfamethoxazole and sulfathalidine; antifungal peptide and derivatives and analogs thereof; apomorphine; aprepitant; arbutin; aripiprazole; ascorbic acid; ascorbyl palmitate; atazanavir; atenolol; atomoxetine; atropine; azathioprine; azelaic acid; azelaic acid; azelastine; azithromycin; bacitracin; bacitracin; beanomicins; beclomefhasone dipropionate; bemegride; benazepril; bendroflumethiazide; benzocaine; Benzoic acid with a keratolytic agent; benzonatate; benzophenone; benztropine; bepridil; beta-hydroxy acids; beta-lactams including penicillin, cephalosporin, and carbapenems such as carbapenem, imipenem, and meropenem; betamethasone dipropionate; betamethasone valerate; brimonidine; brompheniramine; bupivacaine; buprenorphine; bupropion; burimamide; butenafine; Butenafine; butoconazole; Butoconazole; cabergoline; caffeic acid; caffeine; calcipotriene; camphor; Cancidas; candesartan cilexetil; capsaicin; carbamazepine; Caspofungin; cefditoren pivoxil; cefepime; cefpodoxime proxetil; celecoxib; cetirizine; cevimeline; chitosan; chlordiazepoxide; chlorhexidine; chloroquine; chlorothiazide; chloroxylenol; chlorpheniramine; chlorpromazine; chlorpropamide; ciclopirox; Ciclopirox (ciclopirox olamine); cilostazol; cimetidine; cinacalcet; ciprofloxacin; citalopram; citric acid; Citronella oil; cladribine; clarithromycin; clemastine; clindamycin; clioquinol; clobetasol propionate; clomiphene; clonidine; clopidogrel; Clortrimazole; clotrimazole; Clotrimazole; clozapine; cocaine; Coconut oil; codeine; colistin; colymycin; cromolyn; crotamiton; Crystal violet; cyclizine; cyclobenzaprine; cycloserine; cytarabine; dacarbazine; dalfopristin; dapsone; daptomycin; daunorubicin; deferoxamine; dehydroepiandrosterone; delavirdine; desipramine; desloratadine; desmopressin; desoximetasone; dexamethasone; dexmedetomidine; dexmethylphenidate; dexrazoxane; dextroamphetamine; diazepam; dicyclomine; didanosine; dihydrocodeine; dihydromorphine; diltiazem; diphenhydramine; diphenoxylate; dipyridamole; disopyramide; dobutamine; dofetilide; dolasetron; donepezil; dopa esters; dopamine; dopamnide; dorzolamide; doxepin; doxorubicin; doxycycline; doxylamine; doxypin; duloxetine; dyclonine; echinocandins; econazole; Econazole; eflormthine; eletriptan; emtricitabine; enalapril; ephedrine; epinephrine; epinine; epirubicin; eptifibatide; ergotamine; erythromycin; escitalopram; esmolol; esomeprazole; estazolam; estradiol; ethacrynic acid; ethinyl estradiol; etidocaine; etomidate; famciclovir; famotidine; felodipine; fentanyl; Fenticonazole; ferulic acid; fexofenadine; flecainide; fluconazole; Fluconazole; flucytosiine; Flucytosine or 5-fluorocytosine; fluocinolone acetonide; fluocinonide; fluoxetine; fluphenazine; flurazepam; fluvoxamine; formoterol; furosemide; galactarolactone; galactonic acid; galactonolactone; galactose; galantamine; gatifloxacin; gefitinib; gemcitabine; gemifloxacin; gluconic acid; glycolic acid; glycolic acid; glycopeptides such as vancomycin and teicoplanin; griseofulvin; Griseofulvin; guaifenesin; guanethidine; haloperidol; haloprogin; Haloprogin; herbal extract, an alkaloid, a flvanoid, Abafungin; hexylresorcinol; homatropine; homosalate; hydralazine; hydrochlorothiazide; hydrocortisone; hydrocortisone 17-butyrate; hydrocortisone 17-valerate; hydrocortisone 21 -acetate; hydromorphone; hydroquinone; hydroquinone monoether; hydroxyzine; hyoscyamine; hypoxanthine; ibuprofen; ichthammol; idarubicin; imatinib; imipramine; imiquimod; indinavir; indomethacin; Iodine; irbesartan; irinotecan; Isavuconazole; Isoconazole; isoetharine; isoproterenol; itraconazole; Itraconazole; kanamycin; ketamine; ketanserin; ketoconazole; ketoprofen; ketotifen; kojic acid; labetalol; lactic acid; lactobionic acid; lactobionic acid; lamivudine; lamotrigine; lansoprazole; lemon myrtle; letrozole; leuprolide; levalbuterol; levofloxacin; lidocaine; lincosamides such as lincomycin and clindamycin; linezolid; lobeline; loperamide; losartan; loxapine; lucensomycin; lysergic diethylamide; macrolides or ketolides such as erythromycin, azithromycin, clarithromycin, and telithromycin; mafenide; malic acid; maltobionic acid; mandelic acid; mandelic acid; maprotiline; mebendazole; mecamylamine; meclizine; meclocycline; memantine; menthol; meperidine; mepivacaine; mercaptopurine; mescaline; metanephrine; metaproterenol; metaraminol; metformin; methadone; methamphetamine; methotrexate; methoxamine; methyl nicotinate; methyl salicylate; methyldopa esters; methyldopamide; methyllactic acid; methylphenidate; metiamide; metolazone; metoprolol; metronidazole; mexiletine; Micafungin; miconazole; Miconazole; midazolam; midodrine; miglustat; minocycline; minoxidil; mirtazapine; mitoxantrone; moexiprilat; molindone; monobenzone; monolactams such as penicillin G, penicillin V, methicillin, oxacillin, cloxacillin, dicloxacillin, nafcillin, ampicillin, amoxicillin, carbenicillin, ticarcillin, meziocillin, piperacillin, azlocillin, temocillin, cepalothin, cephapirin, cephradine, cephaloridine, cefazolin, cefamandole, cefuroxime, cephalexin, cefprozil, cefaclor, loracarbef, cefoxitin, cefmetazole, cefotaxime, ceftizoxime, ceftriaxone, cefoperazone, ceftazidime, cefixime, cefpodoxime, ceftibuten, cefdinir, cefpirome, cefepime, and astreonam; morphine; moxifloxacin; moxonidine; mupirocin; nadolol; naftifine; Naftifine; nalbuphine; nalmefene; naloxone; naproxen; natamycin; Neem Seed Oil; nefazodone; nelfinavir; neomycin; nevirapine; N-guanylhistamine; nicardipine; nicotine; nifedipine; nikkomycins; nimodipine; nisoldipine; nizatidine; norepinephrine; nystatin; nystatin; octopamine; octreotide; octyl methoxycinnamate; octyl salicylate; ofloxacin; olanzapine; Olive leaf extract; olmesartan medoxomil; olopatadine; omeprazole; Omoconazole; ondansetron; Orange oil; oxazolidinones such as linezolid; oxiconazole; Oxiconazole; oxotremorine; oxybenzone; oxybutynin; oxycodone; oxymetazoline; padimate O; palmarosa oil; palonosetron; pantothenic acid; pantoyl lactone; paroxetine; patchouli; pemoline; penciclovir; penicillamine; penicillins; pentazocine; pentobarbital; pentostatin; pentoxifylline; pergolide; perindopril; permethrin; phencyclidine; phenelzine; pheniramine; phenmetrazine; phenobarbital; phenol; phenoxybenzamine; phenpropimorph; phentolamine; phenylephrine; phenylpropanolamine; phenytoin; phosphonomycin; physostigmine; pilocarpine; pimozide; pindolol; pioglitazone; pipamazine; piperonyl butoxide; pirenzepine; Piroctone; piroctone olamine; podofdox; podophyllin; Polygodial; polyhydroxy acids; polymyxin; Posaconazole; pradimicins; pramoxine; pratipexole; prazosin; prednisone; prenalterol; prilocaine; procainamide; procaine; procarbazine; promazine; promethazine; promethazine propionate; propafenone; propoxyphene; propranolol; propylthiouracil; protriptyline; pseudoephedrine; pyrethrin; pyrilamine; pyrimethamine; quetiapine; quinapril; quinethazone; quinidine; quinolones such as nalidixic acid, oxolinic acid, norfloxacin, pefloxacin, enoxacin, ofloxacin, levofloxacin, ciprofloxacin, temafloxacin, lomefloxacin, fleroxacin, grepafloxacin, sparfloxacin, trovafloxacin, clinafloxacin, gatifloxacin, moxifloxacin, sitafloxacin, besifloxacin, besifloxaxin, clintafloxacin, ganefloxacin, gemifloxacin and pazufloxacin; quinupristin; rabeprazole; Ravuconazole; reserpine; resorcinol; retinal; retinoic acid; retinol; retinyl acetate; retinyl palmitate; ribavirin; ribonic acid; ribonolactone; rifampin; rifamycins such as rifampicin (also called rifampin), rifapentine, rifabutin, bezoxazinorifamycin and rifaximin; rifapentine; rifaximin; riluzole; rimantadine; risedronic acid; risperidone; ritodrine; rivasfigmine; rizatriptan; ropinirole; ropivacaine; salicylamide; salicylic acid; salicylic acid; salmeterol; scopolamine; selegiline; Selenium; selenium sulfide; serotonin; Sertaconazole; sertindole; sertraline; sibutramine; sildenafil; silk fibroin; sordarins; sotalol; streptogramins such as quinupristin and daflopristin; streptomycin; strychnine; sulconazole; Sulconazole; sulfabenz; sulfabenzamide; sulfabromomethazine; sulfacetamide; sulfachlorpyridazine; sulfacytine; sulfadiazine; sulfadimethoxine; sulfadoxine; sulfaguanole; sulfalene; sulfamethizole; sulfamethoxazole; sulfanilamide; sulfapyrazine; sulfapyridine; sulfasalazine; sulfasomizole; sulfathiazole; sulfisoxazole; tadalafil; tamsulosin; tartaric acid; tazarotene; Tea tree oil - ISO 4730 (Oil of Melaleuca, Terpinen-4-ol type”); tegaserol; telithromycin; telmisartan; temozolomide; tenofovir disoproxil; terazosin; terbinafine; Terbinafine; terbutaline; terconazole; Terconazole; terfenadine; tetracaine; tetracycline; tetracyclines such as tetracycline, chlortetracycline, demeclocycline, minocycline, oxytetracycline, methacycline, doxycycline; tetrahydrozoline; theobromine; theophylline; thiabendazole; thioridazine; thiothixene; thymol; tiagabine; timolol; tinidazole; tioconazole; Tioconazole; tirofiban; tizanidine; tobramycin; tocainide; tolazoline; tolbutamide; tolnaftate; Tolnaftate; tolterodine; tramadol; tranylcypromine; trazodone; triamcinolone acetonide; triamcinolone diacetate; triamcinolone hexacetonide; triamterene; triazolam; triclosan; triclosan; Triclosan; triflupromazine; trimethoprim; trimethoprim; trimipramine; tripelennamine; triprolidine; tromethamine; tropic acid; tyramine; undecylenic acid; Undecylenic acid; urea; urocanic acid; ursodiol; vardenafil; venlafaxine; verapamil; vitamin C; vitamin E acetate; voriconazole; Voriconazole; warfarin; xanthine; zafirlukast; zaleplon; zinc pyrithione; Zinc Selenium sulfide; ziprasidone; zolmitriptan; Zolpidem; WS-3; WS-23; menthol; 3-substituted-P-menthanes; N-substituted-P-menthane- 3-carboxamides; isopulegol; 3-(1- menthoxy)propane-l,2-diol; 3-(1-menthoxy)-2-methylpropane-l,2-diol; p-menthane-2,3-diol; p- menthane-3,8-diol; 6-isopropyl-9-methyl-l,4-dioxaspiro[4,5]decane-2-methanol; menthyl succinate and its alkaline earth metal salts; trimethylcyclohexanol; N-ethyl- 2-isopropyl-5- methylcyclohexanecarboxamide; Japanese mint oil; peppermint oil; menthone; menthone glycerol ketal; menthyl lactate; 3-(1-menthoxy)ethan-l-ol; 3-(l-menthoxy)propan-l-ol; 3-(1- menthoxy)butan-loi; 1-menthylacetic acid N-ethylamide; 1-menthyl-4-hydroxypentanoate; 1- menthyl-3-hydroxybutyrate; N,2,3-trimethyl-2-(-1 -methylethyl)-butanamide; n-ethyl-t-2-c-6 nonadienamide; N,N-dimethyl-menthyl succinamide; menthyl pyrrolidone carboxylate; aloe; avocado oil; green tea extract; hops extract; chamomile extract; colloidal oatmeal; calamine; cucumber extract; sodium palmate; sodium palm kernelate; butyrospermum parkii (i.e., shea butter); menthe piperita (i.e.; peppermint) leaf oil; sericin; pyridoxine (a form of vitamin B6); retinyl palmitate and/or other forms of vitamin A; tocopheryl acetate and/or other forms of vitamin E; lauryl laurate; hyaluronic acid; aloe barbadensis leaf juice powder; euterpe oleracea (i.e., acai berry) fruit extract; riboflavin (i.e., vitamin B2); thiamin HC1 and/or other forms of vitamin Bl; ethylenediaminetetraacetic acid (EDTA); citrate; ethylene glycol tetraacetic acid (EGTA); l,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA); diethylene triamine pentaacetic acid (DTPA); 2,3-dimercapto-l-propanesulfonic acid (DMPS); dimercaptosuccinic acid (DMSA); a-lipoic acid; salicylaldehyde isonicotinoyl hydrazone (SIH); hexyl thioethylamine hydrochloride (HTA); desferrioxamine; ascorbic acid (vitamin C); cysteine; glutathione; dihydrolipoic acid; 2-mercaptoethane sulfonic acid; 2-mercaptobenzimidazole sulfonic acid; 6- hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; sodium metabisulfite; vitamin E isomers such as a-, b-, g-, and d-tocopherols and a-, b-, g-, and d-tocotrienols; polyphenols such as 2- tert-butyl-4-methyl phenol, 2-tert-butyl- 5-methyl phenol, and 2-tert-butyl-6-methyl phenol; butylated hydroxyanisole (BHA) such as 2-tert-butyl-4-hydroxyanisole and 3-tert-butyl-4- hydroxyanisole; butylhydroxytoluene (BEIT); tert-butylhydroquinone (TBHQ); ascorbyl palmitate; n-propyl gallate; soy extract; soy isoflavones; retinoids such as retinol; kojic acid; kojic dipalmitate; hydroquinone; arbutin; transexamic acid; vitamins such as niacin and vitamin C; azelaic acid; linolenic acid and linoleic acid; placertia; licorice; and extracts such as chamomile and green tea; hydrogen peroxide; zinc peroxide; sodium peroxide; hydroquinone; 4- isopropylcatechol; hydroquinone monobenzyl ether; kojic acid; lactic acid; ascorbyl acid and derivatives such as magnesium ascorbyl phosphate; arbutin; licorice root; dihydroxyacetone (DHA); glyceryl aldehyde; tyrosine and tyrosine derivatives such as malyltyrosine, tyrosine glucosinate, and ethyl tyrosine; phospho-DOPA; indoles and derivatives; glucosamine; N-acetyl glucosamine; glucosamine sulfate; mannosamine; N-acetyl mannosamine; galactosamine; N- acetyl galactosamine; N-acyl amino acid compounds (e.g., N- undecylenoyl-L-phenylalanine); flavonoids such as quercetin, hesperidin, quercitrin, rutin, tangeritin, and epicatechin; CoQIO; vitamin C; hydroxy acids including C2 -C30 alpha-hydroxy acids such as glycolic acid, lactic acid, 2-hydroxy butanoic acid, malic acid, citric acid tartaric acid, alpha-hydroxyethanoic acid, hydroxycaprylic acid and the like; beta hydroxy acids including salicylic acid and polyhydroxy acids including gluconolactone (G4); retinoic acid; gamma-linolenic acid; ultraviolet absorber of benzoic acid system such as para-aminobenzoic acid (hereinafter, abbreviated as PABA), PABA monoglycerin ester, N,N-dipropoxy PABA ethyl ester, N,N-diethoxy PABA ethyl ester, N,N-dimethyl PABA ethyl ester, N,N-dimethyl PABA butyl ester, and N,N-dimethyl PABA methyl ester and the like; ultraviolet absorber of anthranilic acid system such as homomenthyl-N-acetyl anthranilate and the like; ultraviolet absorber of salicylic acid system such as amyl salicylate, menthyl salicylate, homomenthyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, p-isopropanol phenyl salicylate and the like; ultraviolet absorber of cinnamic acid system such as octyl cinnamate, ethyl-4-isopropyl cinnamate, methyl-2, 5-diisopropyl cinnamate, ethyl-2, 4- diisopropyl cinnamate, methyl-2, 4-diisopropyl cinnamate, propyl-p-methoxy cinnamate, isopropyl-p-methoxy cinnamate, isoamyl-p-methoxy cinnamate, octyl-p-methoxy cinnamate(2- ethylhexyl-p-methoxy cinnamate), 2-ethoxyethyl-p-methoxy cinnamate, cyclohexyl-p-methoxy cinnamate, ethyl-a-cyano-p-phenyl cinnamate, 2-ethylhexyl-a-cyano-P-phenyl cinnamate, glyceryl-mono-2-ethylhexanoyl-dipara-methoxy-cinnamate, methyl bis(trimethylsiloxane)silylisopentyl trimethoxy cinnamate and the like; 3-(4’-methylbenzylidene)- d, 1 -camphor; 3-benzylidene-d,l-camphor; urocanic acid, urocanic acid ethyl ester; 2-phenyl-5 - methylbenzoxazole; 2,2’-hydroxy-5-methylphenylbenzotriazole; 2-(2’-hydroxy-5’-t- octylphenyl)benzotriazole; 2-(2’-hydroxy-5’-methylphenylbenzotriazole; dibenzaladine; dianisoylmethane; 4-methoxy-4’-t-butyldibenzoylmethane; 5-(3,3-dimethyl-2-norbornylidene)-3 - pentane-2-one; dimorpholinopyridazinone; titanium oxide; particulate titanium oxide; zinc oxide; particulate zinc oxide; ferric oxide; particulate ferric oxide; ceric oxide; inorganic sunscreens such as tianium dioxide and zinc oxide; organic sunscreens such as octyl- methyl cinnamates and derivatives thereof; retinoids; vitamins such as vitamin E, vitamin A, vitamin C (ascorbic acid), vitamin B, and derivatives thereof such as vitamin E acetate, vitamin C palmitate, and the like; antioxidants including alpha hydroxy acid such as glycolic acid, citric acid, lactic acid, malic acid, mandelic acid, ascorbic acid, alpha-hydroxybutyric acid, alpha- hydroxyisobutyric acid, alpha-hydroxyisocaproic acid, atrrolactic acid, alpha- hydroxyisovaleric acid, ethyl pyruvate, galacturonic acid, glucopehtonic acid, glucopheptono-1 ,4-lactone, gluconic acid, gluconolactone, glucuronic acid, glucurronolactone, glycolic acid, isopropyl pyruvate, methyl pyruvate, mucic acid, pyruvia acid, saccharic acid, saccaric acid 1 ,4-lactone, tartaric acid, and tartronic acid; beta hydroxy acids such as beta-hydroxybutyric acid, beta-phenyl-lactic acid, beta-phenylpyruvic acid; botanical extracts such as green tea, soy, milk thistle, algae, aloe, angelica, bitter orange, coffee, goldthread, grapefruit, hoellen, honeysuckle, Job's tears, lithospermum, mulberry, peony, puerarua, rice, and safflower; 21-acetoxypregnenolone; alclometasone; algestone; amcinonide; beclomethasone; betamethasone; budesonide; chloroprednisone; clobetasol; clobetansone; clocortolone; cloprednol; corticosterone; cortisone; cortivazol; deflazacort; desonide; desoximetasone; dexamethasone; diflorasone; diflucortolone; difluprednate; enoxolone; fluazacort; flucloronide; flumethasone flunisolide; fluocinolone acetonide; fluocinonide; fluocortin butyl; fluocortolone; fluorometholone; fluperolone acetate; fluprednidene acetate; fluprednisolone; flurandrenolide; fluticasone propionate; formocortal; halcinonide; halobetasol propionate; halometasone; halopredone acetate; hydrocortamate; hydrocortisone; loteprednol etabonate; mazipredone; medrysone; meprednisone; methylprednisolone; mometasone furcate; paramethosone; prednicarbate; prednisolone; prednisolone 25-diethylamino-acetate; prednisolone sodium phosphate; prednisone; prednival; prednylidene; rimexolone; tixocortol; triamcinolone; triamcinolone acetonide; triamcinolone benetonide; triamcinolone hexacetonide; COX inhibitors such as salicylic acid derivatives (e.g., aspirin, sodium salicylate, choline magnesium trisalicylate, salicylate, diflunisal, sulfasalazine and olsalazine); para-aminophenol derivatives such as acetaminophen; indole and indene acetic acids such as indomethacin and sulindac; heteroaryl acetic acids such as tolmetin, dicofenac and ketorolac; arylpropionic acids such as ibuprofen, naproxen, flurbiprofen, ketoprofen, fenoprofen and oxaprozin; anthranilic acids (fenamates) such as mefenamic acid and meloxicam; enolic acids such as the oxicams (piroxicam, meloxicam); alkanones such as nabumetone; diarylsubstituted furanones such as refecoxib; diaryl-substituted pyrazoles such as celecoxib; indole acetic acids such as etodolac; sulfonanilides such as nimesulide; selenium sulfide; sulfur; sulfonated shale oil; salicylic acid; coal tar; povidone-iodine, imidazoles such as ketoconazole, dichlorophenyl imidazolodioxalan, clotrimazole, itraconazoie, miconazole, climbazole, tioconazole, sulconazole, butoconazole, fluconazole, miconazolenitrite; anthralin; piroctone olamine (Octopirox); ciclopirox olamine; anti-psoriasis agents; vitamin A analogs; corticosteroids; and any combinations thereof, including nanoparticulate forms or nanoparticulate compositions comprising any of the aforementioned active agents.

[0040] Other definitions for selected terms used herein may be found within the detailed description of the invention or in the examples, and these definitions apply throughout. Unless otherwise defined, all other scientific and technical terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which the invention belongs.

DETAILED DESCRIPTION

[0041] Polymer blends of the present invention show exceptional potential as a biomaterial for both drug delivery and tissue engineering applications.

[0042] The present inventors have surprisingly found that polymer compositions comprising blends of PDO and LCL exhibit favourably reduced degradation times compared to LCL, without losing the desirable elastomeric behaviour of LCL, producing a well-balanced biomedical polymer with lower degradation time but similar (or surprisingly even higher) mechanical performance than LCL. Considering the performance of native tendon tissue, a material with the ability to withstand high deformation is an ideal characteristic for biomedical applications ¹⁸ . [0043] Although PCL and LCL copolymers show good mechanical flexibility, their slow degradation rate is incompatible with applications in tendon tissue regeneration (2-3 months is the ideal degradation time for tendon tissue engineered scaffolds ¹⁸ ).

[0044] In one embodiment, the invention described herein provides a biocompatible polymer composition, wherein the polymer composition is biodegradable and wherein the polymer composition comprises, PDO and LCL.

[0045] In one embodiment, the invention described herein provides a biocompatible polymer composition, wherein the polymer composition is biodegradable, wherein the polymer composition comprises, PDO and LCL, and wherein the PDO is dispersed as droplets within an LCL matrix.

[0046] In one embodiment, the invention described herein provides a biocompatible polymer composition, wherein the polymer composition is biodegradable and wherein the polymer composition comprises, PDO and LCL, for a biomedical application or, for use in a biomedical application or, when used in a biomedical application.

[0047] In some embodiments, the weight ratio of PDO/LCL in the compositions of the invention is within the range of about; 99/1 to 1/99, 98/2 to 2/98, 97/3 to 3/97, 96/4 to 4/96, 95/5 to 5/95, 94/6 to 6/94, 93/7 to 7/93, 92/8 to 8/92, 91/9 to 9/91 , 90/10 to 10/90, 89/11 to 11/89, 88/12 to 12/88, 87/13 to 13/87, 86/14 to 14/86, 85/15 to 15/85, 84/16 to 16/84, 83/17 to 17/83, 82/18 to

18/82, 81/19 to 19/81 , 80/20 to 20/80, 79/11 to 21/79, 78/22 to 22/78, 77/23 to 23/77, 76/24 to

24/76, 75/25 to 25/75, 74/26 to 26/74, 73/27 to 27/73, 72/28 to 28/72, 71/29 to 29/71 , 70/30 to

30/70, 69/31 to 31/69, 68/32 to 32/68, 67/33 to 33/67, 66/34 to 34/66, 65/35 to 35/65, 64/36 to

36/64, 63/37 to 37/63, 62/38 to 38/62, 61/39 to 39/61 , 60/40 to 40/60, 59/41 to 41/59, 58/42 to

42/58, 57/43 to 43/57, 56/44 to 44/56, 55/45 to 45/55, 54/46 to 46/54, 53/47 to 47/53, 52/48 to

48/52, or 51/49 to 49/51 , or wherein the weight ratio of PDO/LCL in the composition is about 50/50.

[0048] In some embodiments, the weight ratio of PDO/LCL in the compositions of the invention is within the range of; 99/1 to 1/99, 98/2 to 2/98, 97/3 to 3/97, 96/4 to 4/96, 95/5 to 5/95, 94/6 to 6/94, 93/7 to 7/93, 92/8 to 8/92, 91/9 to 9/91 , 90/10 to 10/90, 89/11 to 11/89, 88/12 to 12/88, 87/13 to 13/87, 86/14 to 14/86, 85/15 to 15/85, 84/16 to 16/84, 83/17 to 17/83, 82/18 to 18/82,

81/19 to 19/81 , 80/20 to 20/80, 79/11 to 21/79, 78/22 to 22/78, 77/23 to 23/77, 76/24 to 24/76,

75/25 to 25/75, 74/26 to 26/74, 73/27 to 27/73, 72/28 to 28/72, 71/29 to 29/71 , 70/30 to 30/70,

69/31 to 31/69, 68/32 to 32/68, 67/33 to 33/67, 66/34 to 34/66, 65/35 to 35/65, 64/36 to 36/64,

63/37 to 37/63, 62/38 to 38/62, 61/39 to 39/61 , 60/40 to 40/60, 59/41 to 41/59, 58/42 to 42/58, 57/43 to 43/57, 56/44 to 44/56, 55/45 to 45/55, 54/46 to 46/54, 53/47 to 47/53, 52/48 to 48/52, or 51/49 to 49/51 , or wherein the weight ratio of PDO/LCL in the composition is 50/50.

[0049] In some embodiments, the weight ratio of PDO/LCL in the composition is within the range of about 20/80 to 80/20.

[0050] In some embodiments, the weight ratio of PDO/LCL in the composition is within the range of 20/80 to 80/20.

[0051] In some embodiments, the weight ratio of PDO/LCL in the composition is about 5/95, or about 10/90, or about 20/80, or about 25/75, or about 30/70, or about 35/65, or about 50/50, or about 70/30 or about 80/20.

[0052] In some embodiments, the weight ratio of PDO/LCL in the composition is 5/95, 10/90, 20/80, 25/75, 30/70, 35/65, 50/50, 70/30, or 80/20.

[0053] In some embodiments, the LCL in the composition is a linear copolymer, a branched copolymer, a grafted copolymer, a star-shaped copolymer, a dendronized or other architecture copolymer, an alternating copolymer, a random or statistical copolymer, or a block copolymer, of lactide and caprolactone monomers.

[0054] In some embodiments, the LCL in the composition is a random copolymer.

[0055] In some embodiments, the LCL in the composition is a poly(L-lactide-co-s-caprolactone) copolymer.

[0056] In some embodiments, the ratio of lactide:caprolactone in the LCL of the composition is about; 5:95, 10:90, 15:85, 20:80, 25:75, 30:70, 35:65, 40:60, 45:55, 50:50, 55:45, 60:40, 65:35, 70:30, 75:25, 80:20, 85:15, 90:10, or 95:5.

[0057] In some embodiments, the ratio of lactide:caprolactone in the LCL of the composition is; 5:95, 10:90, 15:85, 20:80, 25:75, 30:70, 35:65, 40:60, 45:55, 50:50, 55:45, 60:40, 65:35, 70:30, 75:25, 80:20, 85:15, 90:10, or 95:5.

[0058] In some embodiments, the ratio of lactide:caprolactone in the LCL of the composition is about 75:25.

[0059] In some embodiments, the ratio of lactide:caprolactone in the LCL of the composition is 75:25.

[0060] In some embodiments, the average molecular weight of the LCL of the composition is about; 5000, 10,000, 20,000, 30,000, 40,000, 50,000, 60,000, 70,000, 80,000, 90,000, 100,000, 150,000, 200,000, 250,000, 300,000, 350,000, 360,000, 370,000, 380,000, 390,000, 400,000,

410,000, 420,000, 430,000, 440,000, 450,000, 500,000, 550,000, 600,000, 650,000, 700,000,

750,000, 800,000, 850,000, 900,000, 950,000, or 1000,000 Da.

[0061] In some embodiments, the average molecular weight of the LCL of the composition is; 5000, 10,000, 20,000, 30,000, 40,000, 50,000, 60,000, 70,000, 80,000, 90,000, 100,000, 150,000, 200,000, 250,000, 300,000, 350,000, 360,000, 370,000, 380,000, 390,000, 400,000,

410,000, 420,000, 430,000, 440,000, 450,000, 500,000, 550,000, 600,000, 650,000, 700,000,

750,000, 800,000, 850,000, 900,000, 950,000, or 1000,000 Da.

[0062] In some embodiments, the average molecular weight of the LCL of the composition is about 410,000 Da.

[0063] In some embodiments, the average molecular weight of the LCL of the composition is 410,000 Da.

[0064] In some embodiments, the inherent viscosity of the PDO of the composition is about; 0.5, 0.6, 0.7, 0.8, 0.9, 1 , 1.1 , 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1 , 2.2, 2.3, 2.4, 2.5, 2.6,

2.7, 2.8, 2.9, 3.0, 3.1 , 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1 , 4.2, 4.3, 4.4, 4.5, 4.6, 4.7,

4.8, 4.9, 5.0, 5.1 , 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1 , 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8,

6.9, 7.0, 7.1 , 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1 or 8.2 when measured in 1 ,1 ,1 ,3,3,3- Hexafluoro-2-propanol (HFIP) as solvent, at a temperature of 30 °C.

[0065] In some embodiments, the inherent viscosity of the PDO of the composition is; 0.5, 0.6, 0.7, 0.8, 0.9, 1 , 1.1 , 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1 , 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8,

2.9, 3.0, 3.1 , 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1 , 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9,

5.0, 5.1 , 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1 , 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0,

7.1 , 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1 or 8.2 when measured in 1 ,1 ,1 ,3,3,3- Hexafluoro-2-propanol (HFIP) as solvent, at a temperature of 30 °C.

[0066] In some embodiments, the inherent viscosity of the PDO of the composition is about 1.6 when measured in 1 ,1 ,1 ,3,3,3-Hexafluoro-2-propanol (HFIP) as solvent, at a temperature of 30 °C.

[0067] In some embodiments, the inherent viscosity of the PDO of the composition is 1 .6 when measured in 1 ,1 ,1 ,3,3,3-Hexafluoro-2-propanol (HFIP) as solvent, at a temperature of 30 °C.

[0068] In some embodiments, the degree of crystallinity X _c (%) of the composition is within the range of about; 2 to 45, 3 to 44, 4 to 43, 5 to 42, 5 to 41 , 5 to 40, 5 to 39, 5 to 38, 6 to 37, or 7 to 37. [0069] In some embodiments, the degree of crystallinity X _c (%) of the composition is within the range of; 2 to 45, 3 to 44, 4 to 43, 5 to 42, 5 to 41 , 5 to 40, 5 to 39, 5 to 38, 6 to 37, or 7 to 37.

[0070] In some embodiments, the degree of crystallinity X _c (%) of the composition is selected from; about 7, about 23 or about 36.

[0071] In some embodiments, the degree of crystallinity X _c (%) of the composition is selected from; 7, 23 or 36.

[0072] In some embodiments, the degree of crystallinity X _c (%) of the composition is selected from; about 6.5, about 22.6 or about 35.9.

[0073] In some embodiments, the degree of crystallinity X _c (%) of the composition is selected from; 6.5, 22.6 or 35.9.

[0074] In some embodiments, the Young’s modulus (MPa) of the composition is within the range of about; 85 to 420, 100 to 330, 110 to 320, 120 to 310, 130 to 300, or 140 to 300.

[0075] In some embodiments, the Young’s modulus (MPa) of the composition is within the range of; 85 to 420, 100 to 330, 110 to 320, 120 to 310, 130 to 300, or 140 to 300.

[0076] In some embodiments, the Young’s modulus (MPa) of the composition is within the range of about 87 to 402, or within the range of about 144 to 303.

[0077] In some embodiments, the Young’s modulus (MPa) of the composition is within the range of 87 to 402, or within the range of 144 to 303.

[0078] In some embodiments, the Young’s modulus (MPa) of the composition is selected from; 103 ± 16, 138 ± 20, 158 ± 14, 161 ± 32, 186 ± 11 , 189 ± 33, 190 ± 22, 199 ± 20, 270 ± 51 , 279 ± 24, 280 ± 66, 365 ± 24, or 387 ± 15.

[0079] In some embodiments, the Yield strength (MPa) of the composition is within the range of about; 2 to 18, 3 to 13, 4 to 12, 5 to 11 , or 6 to 10.

[0080] In some embodiments, the Yield strength (MPa) of the composition is within the range of; 2 to 18, 3 to 13, 4 to 12, 5 to 11 , or 6 to 10.

[0081] In some embodiments, the Yield strength (MPa) of the composition is within the range of about 6.0 to 16.0, or within the range of about 6.3 to 11.3.

[0082] In some embodiments, the Yield strength (MPa) of the composition is within the range of 6.0 to 16.0, or within the range of 6.3 to 11.3. [0083] In some embodiments, the Yield strength (MPa) of the composition is selected from; 6.58 ± 0.24, 7.04 ± 0.37, 7.49 ± 0.44, 9.00 ± 0.30, 9.00 ± 0.87, 9.50 ± 0.93, 9.67 ± 0.47, 9.74 ± 1.59, 10.73 ± 1.39, 13.04 ± 0.42, 13.52 ± 1.20, 13.61 ±1.45, or 14.86 ± 1 .02.

[0084] In some embodiments, the Ultimate strength (MPa) of the composition is within the range of about; 5 to 35, 7 to 21 , 8 to 20 or 9 to 19.

[0085] In some embodiments, the Ultimate strength (MPa) of the composition is within the range of; 5 to 35, 7 to 21 , 8 to 20 or 9 to 19.

[0086] In some embodiments, the Ultimate strength (MPa) of the composition is within the range of about 9.0 to 35.0 or within the range of about 9.2 to 18.8.

[0087] In some embodiments, the Ultimate strength (MPa) of the composition is within the range of 9.0 to 35.0 or within the range of 9.2 to 18.8.

[0088] In some embodiments, the Ultimate strength (MPa) of the composition is selected from; 9.70 ± 0.49, 11.49 ± 0.86, 11.87 ± 1.25, 14.73 ± 2.51 , 15.42 ± 1.58, 15.87 ± 1.18, 16.55 ± 1.67, 18.03 ± 1 .54, 18.88 ± 0.11 , 21 .88 ± 3.29, 25.73 ± 2.25, 26.00 ± 2.67, or 29.17 ± 4.19.

[0089] In some embodiments, the Elongation at break (%) of the composition is within the range of about; 10 to 450, 12 to 440, 13 to 430, 14 to 420 or 15 to 400.

[0090] In some embodiments, the Elongation at break (%) of the composition is within the range of; 10 to 450, 12 to 440, 13 to 430, 14 to 420 or 15 to 400.

[0091] In some embodiments, the Elongation at break (%) of the composition is selected from; 16.34 ± 0.95, 16.76 ± 1.91 , 177.03 ± 70.20, 219.78 ± 14.38, 231.18 ± 73.91 , 254.55 ± 52.43, 256.59 ± 26.41 , 282.43 ± 41.65, 307.21 ± 15.38, 320.30 ± 29.90, 342.80 ± 32.44, 383.88 ± 68.36, or 407.74 ± 37.98.

[0092] In some embodiments, the PDO of the composition is dispersed as droplets within an LCL matrix and wherein the PDO droplet size is within the range of less than 1 pm to about 20 pm, or less than 1 pm to about 15 pm.

[0093] In some embodiments, the PDO of the composition is dispersed as droplets within an LCL matrix and wherein the PDO droplet size is less than 2 pm.

[0094] In some embodiments, the PDO of the composition is dispersed as droplets within an LCL matrix and wherein the PDO droplet size is selected from a mean droplet size of 0.30 ± 0.09 pm, 0.44 ± 0.13 pm, 0.69 ± 0.19 pm, 0.82 ± 0.23 pm, 1.00 ± 0.36 pm, or 1.01 ± 0.32 pm. [0095] In some embodiments, the second-order rate constant (k) obtained from Beer-Lambert equation via FTIR analysis of the composition under accelerated degradation conditions (AC) is within the range of about 0.0037 to 0.0051 , or is selected from about 0.0041 , about 0.0048 or about 0.0049.

[0096] In some embodiments, the second-order rate constant (k) obtained from Beer-Lambert equation via FTIR analysis of the composition under accelerated degradation conditions (AC) is within the range of 0.0037 to 0.0051 , or is selected from 0.0041 , 0.0048 or 0.0049.

[0097] In some embodiments, the second-order rate constant (k) obtained from Beer-Lambert equation via FTIR analysis of the composition under normal degradation conditions (N) is within the range of about 0.0010 to 0.0040, or is selected from about 0.0019, about 0.0026 or about 0.0030.

[0098] In some embodiments, the second-order rate constant (k) obtained from Beer-Lambert equation via FTIR analysis of the composition under normal degradation conditions (N) is within the range of 0.0010 to 0.0040, or is selected from 0.0019, 0.0026 or 0.0030.

[0099] In some embodiments, the Young’s modulus (MPa), and/or the Yield strength (MPa), and/or the Ultimate strength (MPa) of the composition is increased after 2, 4 or 8 weeks under normal degradation conditions (N), compared to prior to being subjected to the degradation conditions.

[00100] In some embodiments, the Young’s modulus (MPa), and/or the Yield strength (MPa), and/or the Ultimate strength (MPa) of the composition is increased after 1 , 3 or 5 days under accelerated degradation conditions (AC), compared to prior to being subjected to the degradation conditions.

[00101 ] In some embodiments, the composition exhibits dynamic porosity.

[00102] The present inventors have also surprisingly found that the mismatch in degradation rate of PDO/LCL blends arising from the faster degradation rate of PDO compared to LCL produces compositions exhibiting dynamic porosity which may be harnessed for the controlled release of one or a plurality of active agents, or for the controlled and staged sequential release of two different active agents.

[00103] In some embodiments, the composition comprises at least one active agent, optionally wherein the active agent is selected from POSS, a POSS derivative, hydroxyapatite, tricalcium phosphate, silk fibroin, or nanoparticles of any of the aforesaid. [00104] In some embodiments, the composition comprises at least one active agent within the PDO of the composition and/or at least one active agent within the LCL of the composition.

[00105] In some embodiments, the composition comprises a first active agent within the PDO of the composition and a second active agent within the LCL of the composition, wherein the first and the second active agents may be the same or different, and wherein the first and second active agents may be active against the same indication, or the first and second active agents may be active against different indications.

[00106] In some embodiments, the composition is for the manufacture of sutures, suture fasteners, meniscus repair devices, rivets, tacks, staples, screws (including interference screws), bone plates and bone plating systems, surgical mesh, repair patches, slings, cardiovascular patches, orthopaedic pins (including bone filling augmentation material), heart valves and vascular grafts, adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, bone marrow scaffolds, meniscus regeneration devices, ligament and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostats, or in the manufacture of articles for use in existing medical contexts, including drug delivery and controlled release of drugs and other bioactive materials, forming coatings on a wide variety of implantable devices, including stents, catheters, and sensors, in the manufacture of a biodegradable substitute material, or for the manufacture of articles imparting a desirable characteristic or attribute associated with the composition, such as a mechanical or surface property, physical or chemical property, biocompatibility property, degradation property, dynamic porosity property, and/or a stability property.

[00107] In some embodiments, the composition is for use in the manufacture of sutures, suture fasteners, meniscus repair devices, rivets, tacks, staples, screws (including interference screws), bone plates and bone plating systems, surgical mesh, repair patches, slings, cardiovascular patches, orthopaedic pins (including bone filling augmentation material), heart valves and vascular grafts, adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, bone marrow scaffolds, meniscus regeneration devices, ligament and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostats, or in the manufacture of articles for use in existing medical contexts, including drug delivery and controlled release of drugs and other bioactive materials, forming coatings on a wide variety of implantable devices, including stents, catheters, and sensors, in the manufacture of a biodegradable substitute material, or for the manufacture of articles imparting a desirable characteristic or attribute associated with the composition, such as a mechanical or surface property, physical or chemical property, biocompatibility property, degradation property, dynamic porosity property, and/or a stability property.

[00108] In some embodiments, the composition is used in the manufacture of sutures, suture fasteners, meniscus repair devices, rivets, tacks, staples, screws (including interference screws), bone plates and bone plating systems, surgical mesh, repair patches, slings, cardiovascular patches, orthopaedic pins (including bone filling augmentation material), heart valves and vascular grafts, adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, bone marrow scaffolds, meniscus regeneration devices, ligament and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostats, or in the manufacture of articles for use in existing medical contexts, including drug delivery and controlled release of drugs and other bioactive materials, forming coatings on a wide variety of implantable devices, including stents, catheters, and sensors, in the manufacture of a biodegradable substitute material, or for the manufacture of articles imparting a desirable characteristic or attribute associated with the composition, such as a mechanical or surface property, physical or chemical property, biocompatibility property, degradation property, dynamic porosity property, and/or a stability property.

[00109] In some embodiments, the composition is suitable for, intended for use, or used in the manufacture of an article via electrospinning, braiding, knitting, solvent casting, hot melt extrusion or 3D printing.

[00110] In accordance with a particularly preferred embodiment of the present invention, blends of semicrystalline PDO and LCL may be prepared in varying concentrations (PDO/LCL weight ratios of 0/100, 5/95, 10/90, 15/85, 25/75, 30/70, 50/50, 70/30 and 100/0) and formed into films by solvent casting.

[00111] In one embodiment, the invention described herein provides a process for the preparation of a composition, comprising combining suitable quantities of LCL and PDO via hot melt extrusion or via solvent casting.

[00112] In one embodiment, the composition is prepared via solvent casting.

[00113] In one embodiment, the composition is prepared via solvent casting at room temperature. [00114] In one embodiment, the composition is prepared via solvent casting in 1 ,1 ,1 ,3,3,3-Hexafluoro-2-propanol (HFIP).

[00115] In one embodiment, the invention described herein provides a process for the preparation of a composition, comprising LCL and PDO wherein the process comprises;

(i) preparing a first solution of LCL, in an appropriate solvent, and at a predetermined concentration;

(ii) preparing a second solution of PDO, in an appropriate solvent, and at a predetermined concentration;

(iii) combining the first solution with the second solution to form a mixture;

(iv) stirring the mixture for a period of time, until the mixture becomes homogeneous;

(v) degassing the mixture, at an appropriate temperature and pressure; and

(vi) evaporating the solvent in the mixture at an appropriate temperature and pressure.

[00116] In one embodiment, of the process of the invention, the first solution and the second solution are prepared together in a single vessel, containing a single volume of an appropriate solvent so that combining the first solution with the second solution to form a mixture in accordance with step (iii) occurs upon dissolution of the LCL and PDO in the single volume of an appropriate solvent.

[00117] In one embodiment of the process of the invention, the solvent is 1 ,1,1 ,3,3,3- Hexafluoro-2-propanol (HFIP).

[00118] In one embodiment of the process of the invention, the predetermined concentration of the first solution is about 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17,

18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42,

43, 44, 45, 46, 47, 48, 49, or 50 w/v %.

[00119] In one embodiment of the process of the invention, the predetermined concentration of the first solution is 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19,

20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44,

45, 46, 47, 48, 49, or 50 w/v %. [00120] In one embodiment of the process of the invention, the predetermined concentration of the first solution is 10 w/v %.

[00121] In one embodiment of the process of the invention, the predetermined concentration of the second solution is about 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16,

17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 ,

42, 43, 44, 45, 46, 47, 48, 49, or 50 w/v %.

[00122] In one embodiment of the process of the invention, the predetermined concentration of the second solution is 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18,

19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43,

44, 45, 46, 47, 48, 49, or 50 w/v %.

[00123] In one embodiment of the process of the invention, the predetermined concentration of the second solution is 10 w/v %.

[00124] In one embodiment of the process of the invention, the concentration of the LCL in the mixture formed in step (iii) is about 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17,

18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42,

43, 44, 45, 46, 47, 48, 49, or 50 w/v %.

[00125] In one embodiment of the process of the invention, the concentration of the LCL in the mixture formed in step (iii) is 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19,

20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44,

45, 46, 47, 48, 49, or 50 w/v %.

[00126] In one embodiment of the process of the invention, the concentration of the LCL in the mixture formed in step (iii) is 10 w/v %.

[00127] In one embodiment of the process of the invention, the concentration of the PDO in the mixture formed in step (iii) is about 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17,

18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42,

43, 44, 45, 46, 47, 48, 49, or 50 w/v %.

[00128] In one embodiment of the process of the invention, the concentration of the PDO in the mixture formed in step (iii) is 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19,

20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44,

45, 46, 47, 48, 49, or 50 w/v %.

[00129] In one embodiment of the process of the invention, the concentration of the PDO in the mixture formed in step (iii) is 10 w/v %. [00130] In one embodiment of the process of the invention, the concentration of the LCL and the concentration of the PDO in the mixture formed in step (iii) is about 1 , 2, 3, 4, 5, 6, 7, 8,

9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33,

34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, or 50 w/v %.

[00131] In one embodiment of the process of the invention, the concentration of the LCL and the concentration of the PDO in the mixture formed in step (iii) is 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, or 50 w/v %.

[00132] In one embodiment of the process of the invention, the concentration of the LCL and the concentration of the PDO in the mixture formed in step (iii) is 10 w/v %.

[00133] In one embodiment of the process of the invention, the period of time in step (iv) is 3h to 7h.

[00134] In one embodiment of the process of the invention, steps (i) to (iv) are performed at room temperature.

[00135] In one embodiment of the process of the invention, step (v) is performed under vacuum at 70 °C.

[00136] In one embodiment of the process of the invention, step (vi) comprises vacuum drying at 60 °C for 24 h.

[00137] In accordance with the present invention, a range of experimental methods may be used to characterise the polymer blends. Thermal (DSC), morphological (SEM) and mechanical (tensile) properties may be investigated before and during hydrolytic degradation in neutral phosphate-buffered saline (PBS) solution at 37 °C and 70 °C, for up to 16 weeks and 12 days, respectively. The skilled addressee will understand that the properties of the compositions of the present invention may also be characterized by a range of alternative experimental methods to those described herein.

[00138] In accordance with the present invention, cellular performance of polymer blends of the invention may be determined by seeding mouse fibroblasts onto the samples and culturing for 72 hours, before using proliferation assays and confocal imaging. Polymer blends of the invention exhibit good cell viability over 72 hours. Cell attachment has a tendency to decrease with increasing the PDO content, and the skilled addressee will understand that this property provides the opportunity to tune the compositions of the invention to the optimal cell attachment required for a particular application. [00139] In accordance with the present invention, increasing LCL content reduces crystallinity and morphologies of all polymer blends show immiscibility between PDO and LCL. An increase in LCL content causes a decrease in hydrolytic degradation, in both normal and accelerated degradation conditions, indicated by weight loss, induced crystallinity, surface and bulk erosions, and tensile properties. A blend of 30% PDO and 70% LCL (PD03LCL7) results in small PDO droplets uniformly dispersed within the LCL matrix and exhibits toughening behaviour with a notable strain-hardening effect reaching 320% elongation at break (over 3 times the elongation of neat LCL), with an ultimate tensile strength (18.9 MPa) comparable to neat PDO (20.5 MPa).

[00140] The skilled addressee will understand that the immiscibility of PDO and LCL, the relative degradation rates of PDO and LCL and the changes in degree of crystallinity in polymer blends of the invention may be utilized to tune polymer compositions of the invention in order to arrive at the desired degradation rate, and/or dynamic porosity, and/or tensile strength and/or mechanical properties suitable to the particular application.

[00141] The skilled addressee will understand that the inherent immiscible properties and the inherent properties of differing rates of degradation in vivo of the PDO and LCL components of the polymer blends of the present invention mean that the polymer blends of the present invention may be prepared via a number of different methods including but not limited to solvent casting and hot melt extrusion methods. The skilled addressee will understand that the polymer blends of the present invention may be prepared via alternative means to those described herein.

[00142] The polymer blends of the present invention may also be employed in a number of different manufacturing and/or fabricating techniques for the manufacture of articles comprising the polymer blends of the invention, including but not limited to such techniques as electrospinning, braiding, knitting, solvent casting, hot melt extrusion, 3D printing, and/or any of the techniques disclosed in detail in any of the published patent literature including, without limitation, published patents US20040243235A1 , US9757132B2, US8486143B2,

US7824701 B2, US9918826B2, US9918827B2 and US20090306776A1 .

EXAMPLES

Sample Preparation

[00143] Random poly(L-lactide-co-s-caprolactone) copolymer (LCL, lactide:caprolactone 75:25, Mw=410,000 Da) and poly(p-dioxanone) (PDO, h,- _h ^ . dL/g, in HFIP at 30 °C) were supplied by BMG Inc (Japan). Films of PDO/LCL blends with weight ratios of 0/100, 5/95, 10/90, 20/80, 25/75, 30/70, 35/75, 50/50, 70/30 and 100/0 were prepared by solvent casting at room temperature. LCL and PDO were dissolved in 1 ,1 ,1 ,3,3,3-Hexafluoro-2-propanol (HFIP) to form 10 w/v % solutions based on the weight ratios. Polymer-solvent mixtures were stirred for 3h to 7h (higher LCL concentration needs longer mixing time) at room temperature. Once a homogeneous solution was obtained, the solution was briefly degassed under vacuum at 70 °C. The homogenous solution was then poured in a glass petri dish (0 60 mm) and placed in a fume hood for 24 h. Residual solvent was removed by vacuum drying at 60 °C for 24 h and stored in vacuum bag at 5 °C. Prepared blends were named as PDO"X"LCL"Y" whereby "X" and "Y" indicate PDO and LCL fractions, respectively. The PDO/LCL blends with weight ratios of 20/80, 25/75, and 35/75 were only prepared to study tensile properties and morphology before hydrolytic degradation.

Characterisation (General)

[00144] Infrared spectroscopy was performed using a FTIR-ATR spectrometer (Polymer ID analyzer, PerkinElmer) with a 4 cm ^-1 resolution in the range of 400^000 cm ^-1 for determining functional groups.

[00145] Morphology of the blends was studied by scanning electron microscopy (SEM) (Ziess 1555 VP-SEM) using platinum-coated samples at an accelerating voltage of 3 kV. Samples were studied at week 4, 8, and 16 to understand the erosion phenomenon during normal hydrolytic degradation.

[00146] Measurements of tensile properties were performed using miniaturized rectangular specimens with gauge length of 25 mm and width of 5 mm (based on type 5B in BS ISO 527: 2012) and an Instron universal tensile tester (Model 5969, Instron, HighWycombe, UK) equipped with a 500 N load cell. Tensile measurements were performed at room temperature (25 °C) and a cross-head speed of 0.5 mm min ^{-1 20} . Average results of at least 3 test specimens were reported for each type of blend.

[00147] Differential Scanning Calorimeter (DSC) analysis was performed using DSC 8500 (PerkinElmer) under nitrogen atmosphere with a heating rate of 10 °C min ^-1 from 30 °C to 220 °C. The melting temperature (T _m ) and the cold crystallization temperature ( T _c ) were taken as the maximum of the endothermic and exothermic peaks, respectively. The degree of crystallinity (X _c ) was taken from the first heating run and calculated using Equation (1): Where, AH _m is the enthalpy of melting and AH _C is the exothermal crystallisation, determined from DSC, and AH° _m is the enthalpy of melting for 100% crystalline polymer. AH° _m of PDO ²¹ , PLLA ²² and PCL ²³ are considered to be 102.9, 93 and 81.6 J g ^~1 , respectively in accordance with values in the cited literature. Although there is no data available for melt enthalpy of PLLA- co-PCL, according to the mixture law, AH° _m of LCL was calculated as 90.15 J g ¹ based on the PLLA and PCL values.

In vitro hydrolytic degradation tests

[00148] The weight loss of samples during hydrolytic degradation were investigated under accelerated (AC) and normal (N) conditions. AC and N conditions for degradation studies were 70 °C and 37 °C respectively. Specimens with 5 5 0.3 mm ³ surface area and weight of approximately 20 mg were prepared from the cast films. For AC degradation, the specimens were immersed in phosphate buffer at pH of 7.4 and temperature of 70 °C under stirring for 12 days. Under N test conditions, the measurement was carried out at the same pH at 37 °C for 24 weeks. At pre-designated time intervals, samples were removed from solution and gently blotted with a KimWipe® before being vacuum dried at room temperature for 24 h and then weighed. The pH of the medium was also measured. All degradation samples were run in triplicate. The weight loss percentage was calculated using Equation (2):

W -- W

Weight loss percentage (%) = — — - x 100 (2) o

[00149] Where, W ₀ and W represent the initial weight and the weight at time t, respectively. A series of specimens were also collected for studying the hydrolytic degradation through FTIR, DSC and SEM techniques, whereas a series of miniaturized rectangular specimens mentioned above were designed for tensile test under both N and AC conditions. The hydrolytic degradation under N conditions was followed by the aforementioned techniques for 16 weeks.

Cell culture, MTS cell proliferation test and biocompatibility evaluation [00150] C3H10 cells (Thermo Fisher Scientific) were seeded on the surface of PDO,

PD07LCL3, PD05LCL5, PD03LCL7 and LCL in densities of 4x10 ³ cells/well in a 48-well plate. Cells were cultured in Minimal Essential Medium (MEM Alpha, Gibco™) containing 10% fetal bovine serum (FBS, Gibco™) and 1% streptomycin and penicillin mixture. Incubation conditions were 37 °C in a humidified atmosphere containing 5% CO2. [00151] After 1 , 2, and 3 days culture, MTS assay for evaluation of cell proliferation was performed. In accordance with the CellTiter ^® 96 AQueous Non-Radioactive Cell Proliferation Assay kit (Promega, USA), [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-( 4- sulfophenyl)-2H-tetrazolium (MTS)] was added to the medium at planned time points and incubated in a darkroom for 3 h at 37 °C, 5% CO2. Optical density (OD) was measured by a 96- well plate reader (Bio-Rad, Model 680, USA) at a wavelength of 490 mm.

[00152] For confocal laser scanning microscope (CLSM) imaging, cells were then fixed with 4% PFA for 15 min after 3 days culture and washed with PBS after fixation. Cells were permeabilized with 0.1% Triton X-100 in PBS for 5 min at room temperature before being incubated with diluted Hoechst (1/5000) and Rhodamine phalloidin (1/1000) in 0.2% BSA-PBS for 30 min at room temperature. Finally, cells were again washed with PBS before being mounted with Diamond antifade mountant medium and stored at -20 °C. Confocal laser scanning microscopy (CLSM) was then performed using Nikon A1 Si Microscope.

Sample Characterization

FTIR Analysis

[00153] To evaluate the chemical composition of PDO/LCL blends, the FTIR spectra was recorded (Figure 1). The broad band at 3200-3650 cm ^-1 for PDO, PD07LCL3, and PD05LCL5 is due to the associated vibration of the hydroxyl (-OH) group. The sequential bands at 2800- 3000 cm ^-1 are ascribed to C— H stretching of methylene (-CH2) groups in all samples ²³ . The sharp peaks located at 1732 cm ^-1 are attributed to the side chain carbonyl (C=0) stretching vibration of PDO and LCL (at 1755 cm ^-1 ). The peaks at 1050, 1123, and 1202 cm ^-1 belong to C-0 stretching vibrations of PDO and the sequential peaks at 1456, 1431 , and 1369 cm ^-1 represent the -CH bending vibrations of PDO ²³²⁴ . Small shifts in LCL peaks can be seen (Figure 1 B); for instance, the C-0 stretching vibration peaks appear at 1042, 1084, 1129, and 1181 cm ¹ and the sequential peaks of -CH bending vibrations are located at 1456, 1383, and 1357 cm ^{1 24} ’ ²⁵ . The intensity and wave number of functional groups are changed by blending PDO and LCL (Figure 1 B). For instance, the spectra of PD07LCL3 and PD03LCL7 are similar to the spectra of PDO and LCL, respectively, indicating that the spectrum of each blend strongly depends on the ratio of PDO to LCL. However, no new peaks were found in the spectra of blend samples, indicating that no chemical reactions or functionalizations leading to the formation or destruction of existing chemical bonds within each of the component polymers occurred during material preparation process. Crystallinity and melting behaviour

[00154] DSC was used to study the crystallization behaviour and thermal properties of each copolymer (Figure 2). As most processing methods occur under non-isothermal conditions, understanding polymer crystallization under dynamic condition is of considerable importance ²² . Data for melting temperature (7 _m ), enthalpy of melting {AH _m ) and the degree of crystallinity ( _c ) of each polymer as well as peak temperature (7 _CC ) and enthalpy {AH _CC ) for cold crystallization of blends before degradation are reported in Table 1.

Table 1 : Melting temperature, crystallinity and Mechanical properties, of PDO/LCL blends. [00155] Blends show two different melting peaks at 103 °C ( T _m of PDO) and 159 °C ( T _m of LCL), indicating that the PDO/LCL blend is not miscible. Blending PDO with LCL brought their melting temperatures slightly closer together, demonstrating that only partial miscibility can be achieved by changing the polymer ratios ²⁶ . PD05LCL5 showed the most miscibility, in terms of thermal behaviour, due to lowest differences in the T _m of PDO and LCL phases (Table 1).The crystallinity of neat PDO sample (47%) is much higher than neat LCL (11%), showing that polymeric chains of PDO were structured in crystalline lamellae due to their high mobility; conversely, the movement restriction of LCL chains dramatically diminished the crystal formation in neat LCL. The single melting temperature at 163 °C indicates that the LCL crystalline phase is mostly formed by lactide proportion (75%) in neat LCL structure. The crystallization exotherm of around 78 °C in neat PDO and in blends is attributed to the cold crystallization phenomena of PDO. The X _c and AH _m of both neat polymers are reduced by blending them in all weight ratios; however, the values are influenced with the ratio of each polymer. For instance, the X _c and AH _m of PDO in the blends decrease with increasing the LCL proportion (Table 1). This is due to the addition of LCL to PDO resulting in less regularity in the PDO crystalline phase due to dispersion of the LCL copolymer in PDO matrix ⁷ .

Morphological studies

[00156] Figure 3 illustrates the surface and cross-section morphologies of the samples obtained by scanning electron microscopy (SEM). The surface morphology of cast PDO film (Figure 3.1 B) shows substantially greater roughness than the morphology of cast LCL film (Figure 3.1 A), which is influenced by the degree of crystallinity of the two neat polymers. Typical spherulitic texture (inset pattern in Figure 3.1 B) can be seen in the neat PDO film demonstrating its lamellar crystalline nature, while the smooth texture of LCL film shows the domination of an amorphous phase {X _c = 11 .2%) indicated by the DSC results ²⁷ .

[00157] Surface topography impacts cellular behaviour ²⁸ so improved cell attachment can be expected for PDO, compared to LCL films. PD03LCL7 films also exhibit a smooth surface (Figure 3.1 C), however, surface roughness increases with PDO content up to 50 wt% (Figure 3.1 E). Furthermore, the formation of microcracks and pores at the surface of PD07LCL3 (Figure 3.1G) is observed owing to the high phase separation between PDO and LCL. In fact, the proportion of PDO crystalline phase attempted to form the lamellae with spherulitic texture on the surface of PD07LCL3 and the lamellae radiated out from a central nucleating point. Then, the amorphous LCL phase occupies the areas between the lamellae ²⁷ . Such surface morphology can also be caused by the difference in evaporation rate of the solvent from LCL and PDO during the film casting process ²⁹ .

[00158] Although the droplet-matrix morphology can be observed in fractured cross- sections of all blend films, the size and dispersion of droplets are influenced by the degree of immiscibility in the blends. In this regard, PD03LCL7 (Figure 3.1 D) shows the smallest size (less than 2 pm) of PDO droplets with uniform dispersion in LCL matrix, demonstrating lowest immiscibility among the blends. A non-uniform droplet size can be seen for PD05LCL5 (Figure 3.1 F), which may vary from submicron to 10 pm. Without wishing to be bound by theory, we postulate that the droplets in PD05LCL5 are attributable to PDO since it possesses much higher crystallinity than LCL, so PDO polymeric chains fold to form a lamellar crystalline phase through nucleation. PD07LCL3 (Figure 3.1 H) also shows a droplet size distribution with a maximum size of ~15 pm such that the LCL and PDO are assigned to matrix and droplet, respectively. However, a multi-core morphology can be observed inside the large LCL sections (pointed with arrows in Figure 3.1 H), which must be related to the encapsulation of small PDO droplets inside LCL shells. PD03.5LCL6.5 (Figure 3.2A), PD02.5LCL7.5 (Figure 3.2B), PD02LCL8 (Figure 3.2C) show the similar size and dispersion of PDO droplets in LCL matrix observed in PD03LCL7. The similar droplet-matrix morphologies means that comparable mechanical properties should be expected from these samples.

[00159] The cross-section morphologies of PDO10LCL9 and PDO0.5LCL9.5 are shown in Figures 3.2 D and E respectively, which indicate the droplet-matrix morphology is similar to other blends containing PDO < 35 wt%. The effect of PDO wt% on the size of PDO droplets can be observed in Figure 3.2. The droplet sizes in these figures were measured via ImageJ and the results are presented in Table 1.1. As can be seen, the size of the PDO droplets grows with increasing PDO content from 5 to 35 wt% inside the LCL matrix.

Table 1.1 : PDO droplet size for the blends containing 5-35 wt% of PDO.

^* The values are shown as the mean (n = 60) ± standard deviation.

Tensile properties

[00160] Tensile properties and example stress-strain curves of PDO/LCL samples are shown in Table 1 and Figure 4, respectively. Neat PDO has the highest Young’s modulus (376 MPa), yield strength (15.3 MPa) and ultimate strength (20.5 MPa) and fails at 22.7% strain without plastic deformation. This rigid behaviour is related to the high crystallinity of PDO ( X _c = 47.7%), where the crystal lattices in the structure hinder the polymer chain elongation under external tension and eventually the failure occurs soon because of the high stress concentration in the interface of amorphous and crystalline regions. Although LCL is an almost amorphous polymer ( X _c = 11.2%), it has a similar Young’s modulus (337 MPa) to PDO because of its high molecular weight (Mw = 410,000 Da). Neat LCL yields at 6.9 MPa and with further stretching the polymer undergoes plastic deformation with a short quasi-horizontal plateau followed by an increasing strain-hardening stage. This strain-hardening behaviour is caused by the induced crystallinity in the specimen due to the high orientation of polymer chains in the direction of tension. As a result, the LCL sample fails after 107% elongation, indicating a highly ductile behaviour for this copolymer.

[00161] The mechanical properties of blend samples are negatively affected by immiscibility and poor interfacial bonding between LCL and PDO phases, especially for PD07LCL3 and PD05LCL5. From Table 1 , all blends show lower Young’s modulus compared to PDO and LCL; however, the yield strength and elongation at break of PD07LCL3 and PD05LCL5 are also lower than those values for the neat samples. This observation is implicated in the high-level immiscibility in PD07LCL3 and PD05LCL5 confirmed by SEM results (Figure 3.1). The presence of microcracks on the surface of PD07LCL3 (Figure 3.1 G), obstructs stress propagation during tension, inducing brittleness in the sample and resulting in the poorest tensile properties among all samples (Table 1). Correspondingly, PD03LCL7 possesses the highest yield strength, ultimate strength and elongation at break among all blends, indicating that low-level immiscibility causes higher mechanical strengths. PD03LCL7 (Figure 4) shows toughening behaviour like LCL, however, the strain-hardening effect is surprisingly and unexpectedly higher in PD03LCL7 and the tensile stress sharply increases with displacement; samples eventually fail at 18.8 MPa with 320 % elongation. The significantly improved elongation at break appears to result from the uniform and much smaller dispersed PDO phase in LCL matrix (Figure 3.1 D) compared to other blends ³¹ . In fact, the smaller dispersed PDO phase produces a higher interfacial surface between the PDO and LCL matrix; consequently, the small PDO droplets play a role in the load-bearing phase of the blend system in high elongations. In other words, most of the imposed energy in the blends is consumed by orienting the LCL coiled chains and initiating the strain-induced crystallization at the beginning of plastic deformation. By further elongation, a part of the load is absorbed by PDO droplets resulting in decreasing stress concentration on the highly oriented LCL chains, and simultaneously, increasing chain orientation in PDO phase. Therefore, it appears that the PDO phase improves uniform stress propagation and continuously increases crystallinity in the sample. The tensile properties of the PDO/LCL blends with weight ratios of 20/80, 25/75, and 35/75 were also studied to find out the role of PDO droplet in mechanical performance. Similar to PD03LCL7, the uniform and small dispersed PDO phase in LCL matrix (Figure 3.2) also led to high elongation at break strain-hardening behaviour in those blends; however, PD02LCL8 showed the highest elongation at break (383%) among the blends. The elongation at break was decreased for both PD01 LCL9 (254.55 ± 52.43%) and PDO0.5LCL9.5 (282.43 ± 41.65 %) compared with PD02LCL8. However, both blends showed higher Young’s modulus and Ultimate strength than PD02LCL8. This indicates that PDO in very low ratios, such as 5-10 wt%, not only reinforces the LCL matrix in the linear deformation region, but also confers a strong stress-hardening effect in plastic deformation. In vitro hydrolytic degradation

[00162] In vitro degradation investigations are used to provide insight into degradation and erosion behaviours in vivo. The hydrolytic degradation of polymers occurs by erosion of the polymer beginning with cleavage of hydrolytic bonds leading to the formation of acidic by products ³² . It has been postulated that the hydrolysis in semi-crystalline polyesters proceeds in two steps with the first chain scission occurring in the amorphous regions, where diffusion of the hydrolysis medium is easier. The second hydrolysis step then occurs in the crystalline regions ³³ .

[00163] In this study, the hydrolytic degradation in samples were followed by weight loss measurement, FTIR spectra, DSC, SEM, and tensile test.

Degradation Measurement via Weight Loss

[00164] Figure 5A and 5B show the weight loss percentage of the samples in normal (N) and accelerated (AC) degradation conditions. With increase in PDO content, the hydrolytic degradation occurs faster for both AC and N conditions. PDO possesses a higher molar concentration of carbonyl bonds in the repeating chain unit and a lower molecular weight than LCL, resulting in a faster degradation for PDO. Therefore, the neat PDO sample indicated highest weight loss (44% in N, 77% in AC) and the neat LCL showed the lowest values (11% in N, 13% in AC). All samples exhibited non-uniform weight loss under N degradation at the early stages, which is related to the swelling and cleavage of amorphous regions within the polymer ²⁴³² . AC degradation showed a more linear trend due to the rapid diffusion of water molecules in the bulk of the samples leading to faster breakage of the ester bonds. The pH change indicates the level of hydrolytic degradation since a remarkable feature of polyester degradation is the acidic by-products of the hydrolytic breakdown; acidic by-products have also been demonstrated to have an “autocatalytic” effect on hydrolytic degradation ³⁴ . Therefore, faster degradation causes higher concentration of acidic by-products and results in lower pH values, which can be similarly observed in Figure 5C and 5D. As a result, PDO shows the lowest pH values in both N and AC conditions demonstrating the fastest degradation rate among the samples, which is in agreement with weight loss results.

Degradation Measurement via FTIR Analysis

[00165] The hydrolytic degradation kinetics can be observed via the FTIR spectra at various time intervals. The FTIR spectra (Figure 6) have been taken from each sample during 16 weeks and 12 days in N and AC degradation conditions, respectively. No functional group (i.e. peak) was added or removed during degradation of samples under either condition; however, the intensity and peak area of carbonyl groups (C=0) changed, which is typical of hydrolytic sensitivity. The hydrolysis rate can be monitored at different times by examining relative changes in molar absorptivity between the carbonyl peak (C=0) appearing at 1750 cm ^-1 and the methylene peak (C-C) at 1454 cm ^{-1 35} . Following this, the Beer-Lambert law; was implemented and the ratio between the peak area of C=0 (A _C o) and C-C (A _C c) was taken as a measure of concentration of C=0 groups to obtain the hydrolytic degradation kinetic parameters ²⁴³⁶ , with; being the ratios of concentrations of C=0 and C-C at the start of a reaction and at any given time t, and k the second-order rate constant, with k obtained by plotting; [4] _t versus time (t) for N and AC conditions (Figure 7). Results, along with the regression coefficients ( R ² ) of each plot, are reported in Table 2.

Table 2: The second-order rate constant (k) obtained from Beer-Lambert equation and the regression coefficient {R ² ) for each sample.

[00166] The neat PDO shows a higher rate of hydrolysis {k (AC): 0.0052; k (N): 0.0044) than the neat LCL (k (AC): 0.003; k (N): 0.0009); however, by adding LCL proportion the blend samples, the hydrolysis rate constant is decreased in both N and AC degradations. These data suggest that the higher hydrolysis rate in PDO than LCL is due to a higher molar concentration of carbonyl bonds in the repeating chain unit and the higher chain mobility in that polymer. These findings are supported by our weight loss data, as well as previous studies showing PDO to have higher degradation than PLA, PCL and PLA-co-PCL copolymers ²³² . The hydrolysis rate of the blends samples diverges from the more linear trends of neat samples, in particular under N conditions, and is influenced by different compositions of the blends. PD05LCL5 showed the lowest R ² values in both AC and N degradation, indicating the highest deviations from a constant rate of hydrolysis. Almost all the samples indicate higher hydrolysis rate constants in AC compared to N degradation (except PDO which was unchanged), confirming that higher temperatures cause more hydrolysis due to the higher speed of water penetration into the polymer chains.

Degradation Measurement via Crystallinity

[00167] The effect of hydrolytic degradation on crystallinity was investigated for 16 weeks and 12 days in N and AC degradation conditions, respectively. The thermal properties were extracted from the first DSC heating scans (Figure 8) as shown in Tables 3 and 4. Figure 9 shows the variations of X _c of the blends during hydrolytic degradation. From Figure 9A and 9B, a particular crystallinity behaviour is observed for neat PDO in both N and AC conditions; the degree of crystallinity increases rapidly at the beginning and then its rate of increase decelerates after 8 days during AC and 8 weeks during N conditions. The initial attack on irregular amorphous regions eliminates the entangled chains between crystalline zones that decreases conformational hindrances, and because the temperature of the hydrolysis medium (37°C) is greater than the T _g of PDO (approximately -10°C ³³ ), the remaining undegraded chains in the amorphous zones can reorganize and crystallize further. Such increase in crystallinity with time is known as “cleavage-induced crystallization” ³⁷ . Table 3: Thermal properties and crystallinity of PDO/LCL blends during accelerated degradation conditions. Table 4: Thermal properties and crystallinity of PDO/LCL blends during normal degradation conditions.

[00168] The increase in X _c of the neat PDO is limited to 8 weeks during N and 8 days during AC and a plateau trend can be observed for further degradation (Figure 9). This is due to X _c being increased more slowly with time after the most amorphous zones have been eliminated. Similar findings were reported in previous studies on the degradation of PDO sutures ³³ . Also, X _c of the neat LCL steadily increases over both N and AC conditions, indicating that the chain entanglements between the regions are still depleting and the chains are reorganizing to from new crystals. This crystallinity behaviour of the neat LCL is affected by a lower degradation rate of its polymer chains compared to those of PDO, which means the initial attacks on LCL amorphous regions (first stage of degradation) lasts longer than PDO. Although the crystallinity behaviour of neat samples in N and AC conditions are similar, the higher crystallinity values were obtained for AC after 12 days. [00169] PDO/LCL blends also show similar crystallinity trends over time in N and AC degradation conditions (Figure 9). A higher proportion of a polymer results in a higher crystallinity value for that polymer’s phase in the blend. For instance, the X _c of PDO phase in PD07LCL3 sample is higher than in PD05LCL5 and PD03LCL7. Under N degradation conditions (Figure 9A), the X _c of the PDO phase increased up to 4 weeks in all blends, indicating the hydrolytic degradation mainly occurs in the amorphous regions and the undegraded chain fragments restructure themselves from a disordered to an ordered state because of a higher mobility obtained from chain scission in the first degradation stage. The X _c values of PDO phase in all blends are smoothly changed after the week 4, demonstrating that the high level of degradation in amorphous regions creates many short chain segments and oligomers which cannot be reordered to form prefect crystals. The decrease in X _c of PDO phase for PD05LCL5 from week 12 to 16 shows the start of the second stage in degradation where hydrolysis destroys the crystalline lattice ³⁸ .

[00170] Under AC degradation conditions (Figure 9B), the X _c of the PDO phase in PD07LCL3, PD05LCL5, and PD03LCL7 increased up to day 8, day 8 and day 4, respectively, indicating that degradation of the crystalline region starts earlier in PD03LCL7 due to the lesser extent of packed crystalline lattice, allowing easier water penetration into the structure compared to the other blends. Similarly, the crystallinity of the LCL phase increases over time for all blends in both N and AC degradation conditions. The X _c of the LCL phase in PD05LCL5 and PD07LCL3 increases slowly in the first 8 weeks due to the high amount PDO acting as a matrix, so the surrounded LCL phase is partially protected from the hydrolysis and initial attacks in short term degradations. This interpretation is supported by the observation that the X _c of PDO phase in PD05LCL5 and PD07LCL3 increases rapidly in the same time period, indicating the initial hydrolysis concentrated on amorphous regions of PDO phase in the blends.

Degradation Measurement via Morphological studies

[00171] The physical erosion that occurs with hydrolytic degradation of biodegradable polymers is classified as either surface erosion or bulk erosion. While the surface erosion is restricted to the polymer surface, bulk erosion involves mass loss throughout the material ³⁴³⁹ . Surface morphology of LCL was unchanged during 8 weeks immersion in PBS (Figure 10A and

IOB); however, surface pores (size: submicron to ~10 urn) appeared after 16 weeks (Figure

IOC) indicating a stage of surface erosion, potentially to be followed by bulk erosion in the near future. This observation is supported by weight loss data (Figure 2), where sample weight is approximately consistent from week 2 to week 16, but then decreased at week 24.

[00172] In contrast, the surface morphology of PDO (Figure 10D-F) shows high rate of hydrolytic degradation, which can severely compromise mechanical functionality. Bulk erosion and mass loss were observed after 4 weeks due to the large, deep macroholes in the sample. Similar morphologies are observed after 8 and 16 weeks; however, several cracks developed on the surface after 8 weeks (arrows in Figure 10E) followed by microcracks on the spherulitic texture after 16 weeks (arrows in Figure 10F) showing the high degradation rate in the crystalline phase. The erosion phenomenon was controlled by adding LCL to PDO; higher LCL content is linked to lower erosion and degradation rate (Figures 10G-100). PD07LCL3 and PD03LCL7 exhibited the highest and lowest erosion, respectively. The controlled degradation in PD03LCL7 provides a porous structure on the surface (Figures 10M-100) as well as the bulk (Figures 10P-10Q), owing to the erosion of PDO phase. This morphology is favourable for cell attachment, immigration and growth in tissue engineering applications. The dynamically changing porosity of polymer blends of the invention also shows great potential for controlled release of active agents and/or staged or sequential release of at least two different active agents.

Degradation Measurement via Tensile Properties

[00173] The effect of hydrolytic degradation on tensile properties of PDO/LCL blends was studied for 8 weeks and 5 days under normal (N) and accelerated (AC) degradation conditions, respectively. Tensile tests were not conducted for PDO and PD07LCL3 in AC degradations due to their poor mechanical integrity when attempting to mount to the tensile test grips. Similarly, the high degradation rate of PDO and PD07LCL3 limited the N degradation time intervals to week 2. Tensile properties are shown in Figure 11 (with supporting data in Figure 12 and Tables 5 and 6).

[00174] The tensile properties of PDO decreased during 2 weeks of N degradation (Figure 11 A and 11 B). In particular, the yield strength, ultimate strength and elongation at break of PDO reduced by 85%, 86%, and 93%, respectively; however, Young’s modulus only decreased by 14%. Similarly, the yield strength, ultimate strength and elongation at break of PD07LCL3 reduced by 30%, 37%, and 62%, respectively; whereas the Young’s modulus increased by 16%.

[00175] As cleavage-induced crystallization was observed during hydrolytic degradation time, induced crystals increase the stiffness and brittleness of blends. However, the decrease in polymeric chain length and molecular weight of components can increase structural defects, reducing the tensile strength ¹⁶ . This explains the increase and decrease in tensile properties of PD07LCL3 where the Young’s modulus increased but the yield strength, ultimate strength and elongation at break reduced due to the structural defects evident in the PDO phase. Similar effects were observed for PD05LCL5 during the first 2 weeks of degradation, however, the Young’s modulus dramatically declined beyond 2 weeks. Table 5: Tensile properties of PDO/LCL blends during normal degradation conditions. [00176] Elongation at break is closely related to structural defects ¹⁶ ’ ⁴⁰⁴¹ and here we observed greater variation in failure strain compared to other tensile properties. If chain scission occurs slowly, the induced crystallinity can enhance the tensile strength and even failure strain, which was observed in PD03LCL7 and LCL, respectively, for 2 weeks and 8 weeks. Therefore, the effect of induced crystals on tensile properties in LCL appears to overcome the effect of structural defects, due to the slow degradation of sample. Improved properties are in agreement with the intact surface morphology of LCL during 8 weeks degradation time (Figures 10A and 10B), while the reduction of tensile properties in other samples is supported by the surface erosion and bulk degradation (Figure 10). Table 6: Tensile properties of PDO/LCL blends during accelerated degradation conditions.

[00177] In AC conditions, the trends of tensile properties for LCL, PD03LC7 and PD05LCL5 are clearly different compared to the N conditions, due to higher degradation rate at 70 °C. For instance, the tensile properties of LCL improve over the first day before properties begin to reduce with further degradation time (Figures 11 C and 11 D). In fact, the negative effects of structural defects appear after 1 day in AC conditions and profoundly affect all tensile properties of all samples after 3 days. [00178] Ranking blends of the present invention based on tensile properties (from highest to lowest) we come up with the following; PD03LCL7>PD05LCL5>PD07LCL3. The exceptionally enhanced tensile properties of PD03LCL7 in particular, shows great potential for biomaterial applications where high strength and mid-term degradation is desired, similar, if not better performance should be expected for PD02LCL8 based on the observed morphological and mechanical properties (see Figure 3.2 and Table 1 ).

Cytotoxicity and cell atachment

[00179] The MTS proliferation results for 72 hours culture (Figure 13A) show that the surface of the polymer blend materials of the invention support cell attachment and proliferation. The quality of the cell attachment after 72 hours on the surface of the samples is associated with blend composition. PDO indicated the lowest cell population on its surface (Figure 13B). As LCL content increased in the blends, an increase in cell populations can be observed (Figure 10C-10E) with the largest cell population in LCL (Figure 10F). PDO/LCL/nHA nanocomoosites - PD02LCL8-5nHA and PD02LCL8- 10nHA

[00180] PDO/LCL/nHA nanocomposites were prepared by mixing 5 wt% and 10 wt% of nano-hydroxyapatite (nHA) (Sigma-Aldrich, <200 nm particle size (BET), ³97%, synthetic) with PD02LCL8 blend solutions. The nanocomposites were prepared by solvent casting as follows:

[00181] LCL (80 wt%) and PDO (20 wt%) were combined in 1 ,1 ,1 ,3,3,3-hexafluoro-2- propanol (HFIP) to form a 10 w/v% solution with magnetic stirring at room temperature. After 30 minutes, when the polymers were partially dissolved in HFIP, 5 wt% or 10 wt% of nHA nanoparticles were added to HFIP in a separate vessel to prepare a nHA suspension. The HFIP volume used to prepare the nHA suspension was equal to the volume used to prepare the polymer solution. The nHA suspension was stirred for 15 minutes at room temperature before being ultrasonicated by an ultrasonic probe at room temperature to size down any nHA agglomerated particles and disperse them uniformly in the HFIP. The final nHA suspension was then added to the polymer solution gently. The resultant polymer/nHA solution was stirred for 7- 12 hours at room temperature to form a homogenous milky-white solution. The homogenous solution was then ultrasonicated by an ultrasonic probe at room temperature for less than 4 minutes with medium to low power, after which, the solution was stirred for 2-5 minutes to remove any induced bubbles during ultrasonication. Finally, the homogenous solution was then poured into a glass Petri dish (0 60 mm) and placed in a fume hood for 24 h. Residual solvent was removed by vacuum drying at 60 °C for 24 h and the nanocomposite products were stored in a vacuum bag at 5 °C. The nanocomposites containing 5 wt% and 10 wt% of nHA were named PD02LCL8-5nHA and PDO2LCL8-10nHA, respectively.

[00182] The cross-section morphology of PDO2LCL8-10nHA is shown in Figure 14, indicating the uniform dispersion of nanoparticles inside the droplet-matrix morphology of PD02LCL8.

[00183] The tensile properties of PDO/LCL/nHA nanocomposites, listed in Table 7, shows that adding nHA particles increased Young modulus, yield strength and ultimate strength of PD02LCL8, due to a reinforcing effect of the nHA nanoparticles. However, the elongation at break of PD02LCL8 was reduced after adding the nanoparticles, likely due to the high-stress concentration on nHA, resulting in an earlier failure. Table 7: Mechanical properties of PDO/LCL/nHA nanocomposites compared to PD02LCL8.

PDO/LCL/Silk composites - PD02LCL8-5S, PD02LCL8-1QS and PD02LCL8-15S

[00184] PDO/LCL/silk composites were prepared by mixing degummed silk powder (from Bombyx mori silkworms) with PD02LCL8 blend solutions. The composites were prepared by solvent casting as follows:

[00185] LCL (80 wt%) and PDO (20 wt%) were combined in 1 ,1 ,1 ,3,3,3-hexafluoro-2- propanol (HFIP) to form a 10 w/v% solution with magnetic stirring at room temperature. After 30 minutes, when the polymers were partially dissolved in HFIP, 5 wt%, 10 wt% or 15 wt% silk powder was added to HFIP in separate vessel to prepare a silk solution. The HFIP volume used for the silk solution was half of the volume used for the polymer solution. The silk solution was stirred for 15 minutes at room temperature before being ultrasonicated by an ultrasonic probe at room temperature to improve silk dispersion uniformly in the HFIP. The silk solution was then added to the remaining polymer solution gently. The final polymer/silk solution was stirred for 7- 12 hours at room temperature to obtain a homogenous cream-coloured solution. Finally, the homogenous solution was then poured into a glass Petri dish (0 60 mm) and placed in a fume hood for 24 h. Residual solvent was removed by vacuum drying at 60 °C for 24 h and the composite products were stored in a vacuum bag at 5 °C. The composites containing 5 wt%, 10 wt% and 15 wt% of silk powder were named PD02LCL8-5S, PDO2LCL8-10S and PD02LCL8- 15S, respectively. [00186] The tensile properties of the PDO/LCL/silk composites, listed in Table 8, indicate that adding silk powder decreased Young’s modulus and ultimate strength of PD02LCL8, acting as a softener (or plasticizer) inside the PD02LCL8 matrix. This effect is clear in the PD02LCL8- 5S composite since the Young’s modulus decreased sharply from 199 MPa to 103 MPa and the elongation at break improved from 383% to 407% with the addition of only 5 wt% of silk. The Young’s modulus was improved by adding 10 or 15 wt% silk, showing that beyond 5 wt%, silk powder can be agglomerated and reinforce the matrix in the elastic deformation compared to PD02LCL8-5S; however, such agglomeration gave rise to failure points and resulted in a decrease of elongation at break for PDO2LCL8-10S and PD02LCL8-15S compared to PD02LCL8-5S.

Table 8: Mechanical properties of PDO/LCL/Silk composites compared to PD02LCL8.

[00187] Figure 15 shows the silk content and agglomeration inside PD02LCL8-5S (Figure 15A) and PD02LCL8-15S (Figure 15B) composites. [00188] Table 9 shows the melting temperature and enthalpy of PDO and LCL phases for

PD02LCL8, PD02LCL8-5S, PDO2LCL8-10S, and PD02LCL8-15S. Figure 16 shows Differential Scanning Calorimetry (DSC) data for these same four samples.

Table 9: Thermal properties of PD02LCL8, PD02LCL8-5S, PDO2LCL8-10S, and PD02LCL8- 15S. [00189] The melting temperature and enthalpy of the composites decrease upon addition of silk, which is indicative of the decrease in nucleation points as consequence of the plasticizing effect of the silk. This reduction trend also demonstrates the good dispersion and interface bonding of silk in the PD02LCL8 matrix as shown in the SEM images (Figure 15).

GENERAL

[00190] Each document, reference, patent application or patent cited in this text is expressly incorporated herein in their entirety by reference, which means that it should be read and considered by the reader as part of this text. That the document, reference, patent application or patent cited in this text is not repeated in this text is merely for reasons of conciseness.

[00191] Any manufacturer’s instructions, descriptions, product specifications, and product sheets for any products mentioned herein or in any document incorporated by reference herein, are hereby incorporated herein by reference, and may be employed in the practice of the invention.

[00192] The invention described herein may include one or more range of values (eg. size, displacement and field strength etc). A range of values will be understood to include all values within the range, including the values defining the range, and values adjacent to the range which lead to the same or substantially the same outcome as the values immediately adjacent to that value which defines the boundary to the range.

[00193] The present invention is not to be limited in scope by any of the specific embodiments described herein. These embodiments are intended for the purpose of exemplification only. Functionally equivalent products, formulations and methods are clearly within the scope of the invention as described herein.

[00194] Those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications other than those specifically described. The invention includes all such variation and modifications. The invention also includes all of the steps, features, formulations and compounds referred to or indicated in the specification, individually or collectively and any and all combinations or any two or more of the steps or features. REFERENCES

(1) Malm T, Bowald S, Bylock A, Busch Ch, Saldeen T, Enlargement of the Right Ventricular Outflow Tract and the Pulmonary Artery with a New Biodegradable Patch in Transannular Position. EurSurg Res 1994; 26: 298-308. doi: 10.1159/000129349

(2) Yang, K. K.; Wang, X. L; Wang, Y. Z. Poly(p-Dioxanone) and Its Copolymers. J. Macromol. Sci. - Polym. Rev. 2002. https://doi.org/10.1081/MC-120006453.

(3) Balali, S.; Davachi, S. M.; Sahraeian, R.; Shiroud Heidari, B.; Seyfi, J.; Hejazi, I. Preparation and Characterization of Composite Blends Based on Polylactic Acid/Polycaprolactone and Silk. Biomacromolecules 2018, acs.biomac.8b01254. https://doi.org/10.1021/acs.biomac.8b01254.

(4) Maglio, G.; Migliozzi, A.; Palumbo, R.; Immirzi, B.; Volpe, M. G. Compatibilized Poly (E-caprolactone)/Poly (L-lactide) Blends for Biomedical Uses. Macromol. Rapid Commun. 1999, 20 (4), 236-238.

(5) Gardella, L.; Calabrese, M.; Monticelli, O. PLA Maleation: An Easy and Effective Method to Modify the Properties of PLA/PCL Immiscible Blends. Colloid Polym. Sci. 2014, 292

(9), 2391-2398.

(6) Giacobazzi, G.; Rizzuto, M.; Zubitur, M.; Mugica, A.; Caretti, D.; Muller, A. J.

Crystallization Kinetics as a Sensitive Tool to Detect Degradation in Poly(Lactide)/Poly(s- Caprolactone)/ PCL-Co-PC Copolymers Blends. Polym. Degrad. Stab. 2019. https://doi.Org/10.1016/j.polymdegradstab.2019.108939.

(7) Goonoo, N.; Jeetah, R.; Bhaw-Luximon, A.; Jhurry, D. Polydioxanone-Based Bio-

Materials for Tissue Engineering and Drug/Gene Delivery Applications. Eur. J. Pharm. Biopharm. 2015, 97, 371-391 .

(8) Goonoo, N.; Fahmi, A.; Jonas, U.; Gimie, F.; Arsa, I. A.; Benard, S.; Schonherr, FI.; Bhaw-Luximon, A. Improved Multicellular Response, Biomimetic Mineralization, Angiogenesis, and Reduced Foreign Body Response of Modified Polydioxanone Scaffolds for Skeletal Tissue Regeneration. ACS Appl. Mater. Interfaces 2019, 11 (6), 5834-5850.

(9) Cachia, V. V. Bone Fixation Device. Google Patents February 19, 2002.

(10) Bai, W.; Zhang, L.-F.; Li, Q.; Chen, D.-L.; Xiong, C.-D. In Vitro Hydrolytic Degradation of Poly (Para-Dioxanone)/Poly (d, l-Lactide) Blends. Mater. Chem. Phys. 2010, 122 ( 1), 79- 86.

(11) Wang, J.; Ding, S.-D.; Wang, Y.-Z. Preparation of UV-Crosslinked Biodegradable Poly (p- Dioxanone)/Poly (Ethylene Glycol) Films. J. Control. Release 2011, 152.

(12) Thomas, V.; Zhang, X.; Vohra, Y. K. A Biomimetic Tubular Scaffold with Spatially Designed Nanofibers of Protein/PDS® Bio-blends. Biotechnol. Bioeng. 2009, 104 (5), 1025-1033.

(13) Cho, K. J.; Song, D. K.; Oh, S. H.; Koh, Y. J.; Lee, S. H.; Lee, M. C.; Lee, J. H. Fabrication and Characterization of Hydrophilized Polydioxanone Scaffolds for Tissue Engineering Applications. In Key Engineering Materials, Trans Tech Publ, 2007; Vol. 342, pp 289-292.

(14) Pezzin, A. P. T.; Alberda van Ekenstein, G. O. R.; Zavaglia, C. A. C.; Ten Brinke, G.; Duek, E. A. R. Poly(Para-Dioxanone) and Poly(1 -Lactic Acid) Blends: Thermal, Mechanical, and Morphological Properties. J. Appl. Polym. Sci. 2003. https://doi.Org/10.1002/app.11984.

(15) Pezzin, A. P. T.; Duek, E. A. R. Miscibility and Hydrolytic Degradation of Bioreabsorbable Blends of Poly(p-Dioxanone) and Poly(L-Lactic Acid) Prepared by Fusion. J. Appl. Polym. Sci. 2006. https://doi.org/10.1002/app.23646.

(16) Xie, X.; Bai, W.; Tang, C.; Chen, D.; Xiong, C. Effects of Poly (Para-Dioxanone-Co-L- Lactide) on the in Vitro Hydrolytic Degradation Behaviors of Poly (L-Lactide)/Poly (Para- Dioxanone) Blends. J. Mater. Res. 2015, 30 (6), 860-868.

(17) Zhou, X.; Pan, Y.; Liu, R.; Luo, X.; Zeng, X.; Zhi, D.; Li, J.; Cheng, Q.; Huang, Z.; Zhang, H. Biocompatibility and Biodegradation Properties of Polycaprolactone/Polydioxanone Composite Scaffolds Prepared by Blend or Co-Electrospinning. J. Bioact. Compat. Poiym. 2019, 34 (2), 115-130.

(18) Ladd, M. R.; Lee, S. J.; Stitzel, J. D.; Atala, A.; Yoo, J. J. Co-Electrospun Dual Scaffolding System with Potential for Muscle-Tendon Junction Tissue Engineering. Biomaterials 2011, 32(6), 1549-1559. https://doi.Org/10.1016/j.biomaterials.2010.10.038.

(19) Rieu, C.; Picaut, L.; Mosser, G.; Trichet, L. From Tendon Injury to Collagen-Based Tendon Regeneration: Overview and Recent Advances. Curr. Pharm. Des. 2017, 23 { 24), 3483-3506.

(20) Hervy, M.; Santmarti, A.; Lahtinen, P.; Tammelin, T.; Lee, K.-Y. Sample Geometry Dependency on the Measured Tensile Properties of Cellulose Nanopapers. Mater. Des. 2017, 121, 421-429.

(21) Ahlinder, A.; Fuoco, T.; Finne-Wistrand, A. Medical Grade Polylactide, Copolyesters and Polydioxanone: Rheological Properties and Melt Stability. Poiym. Test. 2018, 72, 214- 222.

(22) Torabinejad, B.; Mohammadi-Rovshandeh, J.; Davachi, S. M.; Zamanian, A. Synthesis and Characterization of Nanocomposite Scaffolds Based on Triblock Copolymer of L- Lactide, e-Caprolactone and Nano-Hydroxyapatite for Bone Tissue Engineering. Mater. Sci. Eng. C 2014, 42, 199-210.

(23) Dong, X. T.; Shi, W. T.; Dang, H. C.; Bao, W. Y.; Wang, X. L.; Wang, Y. Z. Thermal, Crystallization Properties, and Micellization Behavior of HEC-g-PPDO Copolymer: Microstructure Parameters Effect. Ind. Eng. Chem. Res. 2012. https://doi.Org/10.1021/ie300873a.

(24) Davachi, S. M.; Kaffashi, B.; Torabinejad, B.; Zamanian, A. In-Vitro Investigation and Hydrolytic Degradation of Antibacterial Nanocomposites Based on PLLA/Triclosan/Nano- Hydroxyapatite. Polymer (Guild†). 2016, 83, 101-110.

(25) Wang, D. K.; Varanasi, S.; Fredericks, P. M.; Hill, D. J. T.; Symons, A. L.; Whittaker, A. K.; Rasoul, F. FT-IR Characterization and Hydrolysis of PLA-PEG-PLA Based Copolyester Hydrogels with Short PLA Segments and a Cytocompatibility Study. J. Poiym. Sci. Part A Poiym. Chem. 2013. https://doi.org/10.1002/pola.26930.

(26) Zare, Y.; Rhee, K. Y. Following the Morphological and Thermal Properties of PLA/PEO Blends Containing Carbon Nanotubes (CNTs) during Hydrolytic Degradation. Compos. Part B Eng. 2019, 175, 107132.

(27) Ravi, M.; Song, S.-H.; Gu, K.-M.; Tang, J.-N.; Zhang, Z.-Y. Effect of Lithium Thiocyanate Addition on the Structural and Electrical Properties of Biodegradable Poly (e- Caprolactone) Polymer Films. Ionics (Kiel). 2015, 21 (8), 2171-2183.

(28) Stevens, L. R.; Harman, D. G.; Gilmore, K. J.; Wallace, G. G. A Comparison of Chemical and Electrochemical Synthesis of PEDOT: Dextran Sulphate for Bio-Application. MRS Online Proc. Libr. Arch. 2015, 1717.

(29) Dhatarwal, P.; Sengwa, R. J. Polymer Compositional Ratio-Dependent Morphology, Crystallinity, Dielectric Dispersion, Structural Dynamics, and Electrical Conductivity of PVDF/PEO Blend Films. Macromol. Res. 2019, 27(10), 1009-1023.

(30) Lugito, G.; Woo, E. M.; Chuang, W.-T. Interior Lamellar Assembly and Optical Birefringence in Poly (Trimethylene Terephthalate) Spherulites: Mechanisms from Past to Present. Crystals 2017, 7(2), 56.

(31) Zhu, W.; Zhang, X.; Feng, Z.; Huang, B. Effect of Ethylene-propylene Copolymer with Residual PE Crystallinity on Mechanical Properties and Morphology of PP/HDPE Blends. J. Appl. Poiym. Sci. 1995, 58 { 3), 551-557.

(32) Mohseni, M.; Hutmacher, D. W.; Castro, N. J. Independent Evaluation of Medical-Grade Bioresorbable Filaments for Fused Deposition Modelling/Fused Filament Fabrication of Tissue Engineered Constructs. Polymers (Basel). 2018, 10 { 1), 40.

(33) Sabino, M. A.; Albuerne, J.; Muller, A. J.; Brisson, J.; Prud’homme, R. E. Influence of in Vitro Hydrolytic Degradation on the Morphology and Crystallization Behavior of Poly (p- Dioxanone). Biomacromolecules 2004, 5(2), 358-370.

(34) Woodard, L. N.; Grunlan, M. A. Hydrolytic Degradation and Erosion of Polyester Biomaterials. ACS Macro Letters. 2018. https://doi.org/10.1021/acsmacrolett.8b00424.

(35) Rowe, M. D.; Eyiler, E.; Walters, K. B. Hydrolytic Degradation of Bio-Based Polyesters: Effect of PH and Time. Polym. Test. 2016, 52, 192-199.

(36) Davachi, S. M.; Kaffashi, B.; Zamanian, A.; Torabinejad, B.; Ziaeirad, Z. Investigating Composite Systems Based on Poly L-Lactide and Poly l-Lactide/Triclosan Nanoparticles for Tissue Engineering and Medical Applications. Mater. Sci. Eng. C2016, 58, 294-309. (37) Lee, S. Y.; Park, J. W.; Yoo, Y. T.; Im, S. S. Hydrolytic Degradation Behaviour and

Microstructural Changes of Poly (Ester-Co-Amide) S. Polym. Degrad. Stab. 2002, 78 (1), 63-71.

(38) Chu, C. C. Hydrolytic Degradation of Polyglycolic Acid: Tensile Strength and Crystallinity Study. J. Appl. Polym. Sci. 1981, 26 (5), 1727-1734. (39) von Burkersroda, F.; Schedl, L.; Gopferich, A. Why Degradable Polymers Undergo

Surface Erosion or Bulk Erosion. Biomaterials 2002, 23 ( 21), 4221^231.

(40) Bai, W.; Chen, D.; Li, Q.; Chen, H.; Zhang, S.; Huang, X.; Xiong, C.-D. In Vitro Hydrolytic Degradation of Poly (Para-Dioxanone) with High Molecular Weight. J. Polym. Res. 2009, 16 (5), 471—480. (41) Bai, Y.; Luo, P.; Wang, P.; Bai, W.; Xiong, C.; Tang, C. Hydrolytic Degradation of

PPDO/PDLLA Blends Containing the Compatibilizer PLADO. J. Polym. Environ. 2013, 21 (4), 1016-1025.