FIELD OF THE INVENTION

[0001] The present invention relates to elastic, stretchable, polymeric surgical repair devices having a radiopaque material dispersed therein and, more particularly, to a method of in vivo monitoring the condition of an internal surgical repair in a living thing in which such repair devices have been surgically inserted within the body to effect the repair.

BACKGROUND OF THE INVENTION

[0002] Following many surgical procedures in a living thing (human or animal) it is important or advantageous to be able to monitor in vivo the condition of surgical repair devices inserted during the procedure in order to monitor the healing progress of the surgical repair. Surgical repairs may fail, require repair or require removal for any number of reasons, including, inter alia, foreign body rejection, poor surgical repair device insertion, surgical repair device stretching or deforming and breaking or failure in some other detrimental fashion. For example, monitoring the healing progress following tendon or cruciate repair using sutures or hernia repairs using mesh or orbital floor repairs using smooth foil implants is particularly desirable.

[0003] Typically useful surgical repair devices include polymeric sutures, which may be monofilamentary or multifilamentary and formed of polyamides or other synthetic polymers. Also in common use are polymeric foil and mesh implants. Foil implants are smooth polyamide or other synthetic polymeric sheets having a thickness from 0.01-2.0 mm. Mesh implants are woven or knit material of open texture formed of polyamide or other synthetic polymeric fabric. SUMMARY OF THE INVENTION

[0004] In accordance with one aspect, the present invention provides a method of in vivo monitoring the condition of an internal body repair in a human or animal in which a radiopaque repair device, having non-absorbable, particulate radiopaque material dispersed therewithin, which device deforms due to stresses of the healing process has been surgically inserted within the body to effect the repair, comprising:

in vivo sensing by a medical practitioner of dimensional deformation or changes to the chemical characteristics of said radiopaque repair device during the post-surgical healing process;

comparing the sensed chemical change or dimensional deformation with a previously developed correlation between said sensed chemical characteristic or dimensional deformation and the value of said chemical characteristic or dimension at which failure occurs of repair devices having comparable size, construction and chemical composition characteristics;

wherein said sensed value of said chemical characteristic or dimension relative to the repair device's failure value of said chemical characteristic or dimension, considered in conjunction with the anticipated time for complete healing of said repair, provides information to said medical practitioner as to the condition of the repair and is indicative of whether medical or surgical intervention is appropriate.

[0005] In another aspect of the invention, there is provided a method wherein said in vivo sensing and comparative analysis occurs repetitively at spaced time intervals subsequent to repair device insertion.

[0006] In still another aspect of the invention, there is provided a method wherein said dimensional deformation of said radiopaque repair device is a decrease in the diameter of said repair device over a predetermined length of device.

[0007] In yet another aspect of the invention, there is provided a method wherein said change in chemical characteristics of said radiopaque repair device is a decrease in the concentration of radiopaque material over a predetermined length of device.

[0008] In another aspect of the invention, there is provided a method wherein said previously developed correlation is an in vivo correlation. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] FIGURE 1 is a cross-sectional view of an extrusion coated multifilament radiopaque suture wherein the suture core comprises a multitude of polyamide filaments twisted or braided together and heat set and the overlying sheath contains substantially uniformly dispersed radiopaque material.

[0010] FIGURE 2 is a cross-sectional view of an extrusion coated multifilament radiopaque suture wherein the suture core comprises a mixture of polyamide filaments and previously extruded bundles comprising a multitude of individual polyamide filaments twisted or braided together, heat set and overcoated with a polyamide sheath containing substantially uniformly dispersed radiopaque material.

[0011] FIGURE 3 is a perspective view of a surgical mesh incorporating substantially uniformly dispersed radiopaque material in the synthetic polymeric fabric.

[0012] FIGURE 4 is a perspective view of a smooth synthetic polymeric foil implant incorporating substantially uniformly dispersed radiopaque material in the synthetic polymeric fabric.

DETAILED DESCRIPTION OF THE INVENTION

[0013] Inasmuch as all but metal surgical repair devices are transparent to visualization, and the use of metal repair devices is frequently undesirable, it has been found that only the use of polymeric repair devices having radiopaque properties provides the capability of monitoring the healing progress of a surgical repair. Polymeric surgical repair devices require a unique combination of physical properties. They must be nonirritating, flexible and exhibit high tensile strength. Additionally, they must retain their physical properties after conventional processing such as sterilization and resterilization. The most frequently used surgical repair devices are polymeric sutures, although other well known polymeric repair devices, including but not limited to polymeric mesh and foil implants, are useful in the monitoring method of the present invention. For ease of description and understanding, the instant method will be described herein primarily using polymeric radiopaque sutures as the polymeric radiopaque surgical repair devices, although the method described is readily adaptable to use with devices other than sutures. One recently developed suitable polymeric radiopaque suture is described in pending U.S. Patent Application Serial No. 14/281,274, filed May 19, 2014 and assigned to the same assignee as the present invention.

[0014] Polymeric sutures must, in addition to the aforementioned physical properties, exhibit high knot strength. Additionally, sutures must retain their physical properties after conventional processing such as dyeing, sterilization and resterilization. Some elasticity is required in the final suture structure to obtain the required knot strength and other properties to allow the suture to meet USP specifications. Sutures may be made radiopaque by incorporating nanoparticle sized radiopaque material uniformly dispersed throughout the entire length of the suture. In one useful suture construction, as described in the aforementioned U.S. patent application, the suture comprises a core of a plurality of twisted Polyamide 66 filaments encased within a sheath of Polyamide 6 in which nanoparticle radiopaque materials, such as tantalum or other radiopaque particles, are substantially uniformly dispersed to provide the desired radiopacity along the entire length of the suture.

[0015] Referring to FIGURE 1, there is shown a cross section of an illustrative radiopaque suture 10 useful in connection with the method of the present invention. Suture 10 comprises a core 12 formed of a multitude of Polyamide 66 fibers 14 and an overcoated Polyamide 6 sheath 16 having nanoparticle sized radiopaque material 18 dispersed throughout the thickness and length of sheath 16. Another form of suture useful in the method of the present invention is shown in FIGURE 2, which illustrates a core 12 formed of previously extruded bundles 20 of Polyamide 66 filaments 14 overcoated with a

Polyamide 6 sheath 16, the core 12 being encased within sheath 16 which has been extruded thereabout, the sheath 16 having nanoparticle sized radiopaque material 18 dispersed throughout its thickness and length. Optionally, core 12 may include, in addition to bundles 20, individual Polyamide 66 filaments 14 to act as a filler in some of the spaces formed between the bundles 20. The sheath-core configuration of the multifilament sutures requires that the polyamide core filaments have at least a 30°C greater melting temperature than the polyamide sheath material to assure that the filaments in the core do not melt during over coating of the sheath. Referring to FIGURE 3, there is shown an illustrative polymeric mesh 30 which is a woven or knit material of open texture formed of polyamide, e.g., Polyamide 6, or other synthetic polymeric fabric. The threads 32 forming the mesh correspond to the radiopaque sutures of FIGURE 1 or 2 and, therefore, include nanoparticle sized radiopaque material 18 dispersed throughout the thickness and length of each thread. Another form of surgical device is shown in FIGURE 4, which illustrates a foil implant 40 comprising a smooth polyamide, e.g., Polyamide 6, or other synthetic polymeric sheet having a thickness from 0.01-2.0 mm and having incorporated within the sheet during its formation nanoparticle sized radiopaque material 18 dispersed throughout the thickness of the sheet.

[0016] It will be appreciated that these forms of radiopaque surgical repair devices are only illustrative of the type of radiopaque surgical repair devices which are useful in the method of the present invention. Other device constructions and other polymeric materials may be used to form radiopaque sutures, meshes, foils, and the like, useful in the method of the present invention, provided that the radiopaque material is substantially uniformly dispersed to provide the desired radiopacity throughout the entire device. The preferred radiopaque material is nanoparticulate tantalum or tantalum oxide, which are known to be highly bioinert and to possess high radiographic density, allowing them to be used at relatively lower concentrations. However, due to the high cost of tantalum compounds, its use may not always be economically practical. Other highly desirable radiopaque materials include titanium, zirconium, silver, bismuth and platinum in elemental, salt or oxide form. Consistent with the foregoing criteria, still other radiopaque materials may be used as well. However, inasmuch as the concentration of radiopaque particles in the device is a function of the radiopacity of the particle selected, some radiopaque materials are unsuitable due to the high concentrations which would be required to achieve the desired radiopacity.

[0017] It is well known that elastic, polymeric sutures stretch and that when they are placed under tension they elongate and can ultimately fail. For example, available data suggests that failure of polyamide sutures occurs generally somewhere between 20% and 30% elongation, depending upon the characteristics of the particular suture. As the suture elongates under stress, the suture diameter decreases thus decreasing the amount of particulate radiopaque material within a fixed length of the suture. It has been found that this decrease in the density or concentration of radiopaque material within the fixed length of the suture as a function of elongation can be measured in vivo for any particular suture. It has also been found that the decrease in suture diameter within a fixed length of the suture as a function of elongation can be measured in vivo for any particular suture. Accordingly, the present invention provides a number of methods for monitoring the progress of healing of a sutured repair within the body of a mammal by quantitative in vivo monitoring the condition of an elastic, stretchable polymeric suture having a radiopaque material substantially uniformly dispersed therein along its length which has been inserted into the body in a surgical procedure. The ultimate goal of the methods is to provide totally reliable in vivo measurement of the healing process following surgical repairs by taking advantage of the change in physical and/or chemical characteristics during healing of surgically inserted radiopaque polymeric, non-absorbable repair devices.

[0018] In one illustrative embodiment, the in vivo monitoring is accomplished using EDM (energy dispersive microscopy - sometimes called energy-dispersive X-ray spectroscopy (EDS) or energy dispersive X-ray analysis (EDXA)) techniques. EDM is an analytical technique used for the elemental analysis or chemical characterization of a sample. It relies upon the interaction of X-rays or a high-energy beam of charged particles and a sample. Upon bombardment with a beam of charged particles, such as electrons or protons or a beam of X-rays, the emission of characteristic X-rays from a material is stimulated. Without wishing to be bound to any particular theory regarding the manner in which EDM functions for elemental analysis, it is generally believed that when materials are exposed to a high energy beam of charged particles, an electron in an inner shell is excited and ejected from the shell while creating an electron hole where the electron was. The removal of an electron in this way makes the electronic structure of the atom unstable, and an electron in an outer, higher energy shell "falls" into the lower orbital to fill the hole left behind. In falling, energy is released in the form of an X-ray. The number and energy of the X-rays emitted can be measured by an energy-dispersive spectrometer. As the energies of the X-rays are characteristic of the energy difference of the two orbitals involved and of the atomic structure of the emitting element, EDM allows the elemental composition of the specimen to be measured.

[0019] There are a limited number of ways that an electron from an outer shell drops into the place of an electron removed by high energy radiation from a primary radiation source. The main transitions are given names: an L→K transition is traditionally called K _a , an M→K transition is called Kp, an M→L transition is called L _a , etc. Each of these transitions yields an X-ray with a characteristic energy and each element has electronic orbitals of characteristic energy. The wavelength of this radiation can be calculated and the radiation can be analyzed, e.g., by separating the wavelengths of the radiation. Once sorted, the intensity of each characteristic radiation is directly related to the amount of each element in the material. This is the basis of a powerful technique in analytical chemistry, wherein the wavelength intensity appears as spectral lines. Thus, for example, a typical L _a line for the detection of radiopaque tantalum appears at a wavelength of 0.1522 nm.

[0020] EDM provides an effective in vivo measurement of the concentration of radiopaque elements, e.g., tantalum, noninvasively within human subjects. In this connection it has been determined that radiation doses required by in vivo EDM are sufficiently low not to be a health concern. It is, of course, true that applying EDM techniques to human bodies rather than to thin, uniform, carefully prepared samples, as in elemental analyses in other than the medical fields, presents several difficulties. For example, sample preparation of human subjects is effectively limited to cleaning the patient's skin and positioning the patient with respect to the source of radiation and detector in the most advantageous geometry possible. On the other hand, the method of the present invention contemplates monitoring and repetitive comparative analyses of the element to be evaluated in a single patient rather than in multiple different patients, and does not require absolute elemental concentration determinations. Accordingly, so long as the variables which can be controlled are controlled, such as identical radiation source and detector, consistent patient positioning and avoidance of superficial skin contamination, many of the anticipated difficulties are avoided.

[0021] Initially, the in vivo relationship between radiopaque material concentration in a fixed length of the suture and corresponding suture elongation is empirically determined, e.g., via cadaver studies, for the particular radiopaque suture to be used. This includes determining the radiopaque material concentration at which suture rupture occurs due to elongation. With this relationship available, it would be prudent for the physician, substantially immediately following surgical repair using radiopaque sutures, to order an EDM study of the sutured repair to measure in vivo the radiopaque material concentration in a fixed length of the suture within the body. This determines the base line concentration of radi opaque material in said suture before any elongation occurs. As used herein, the term "substantially immediately" is intended to refer to a time frame following the surgical procedure which is sufficiently short to avoid suture elongation. This base line

concentration of radiopaque material in the suture is converted, using the previously developed relationship of radiopaque material concentration to corresponding suture elongation, into terms of suture elongation. The physician is primarily concerned with the status of the repair sutures during the period between insertion and full healing. During that period. If elongation of the suture occurs, then the diameter of the suture and/or the thickness of the radiopaque material containing portion of the suture will diminish and the density or amount or concentration of radiopaque material within the fixed length of suture will also diminish. The extent of any elongation of the sutures will be evident by comparing the suture elongation corresponding to each periodically determined radiopaque material concentration measurement to the base line suture elongation, to any previously measured suture elongations and to the suture rupture elongation to determine the condition of the suture relative to its base line and to its rupture elongation at any time during the healing process. This information will allow a physician to determine whether the sutured repair is healing properly or is damaged and, if the latter, the seriousness of the damage and whether medical or surgical intervention is appropriate. Alternatively, particularly where healing occurs over a shorter term, the physician may elect to make only one in vivo EDM measurement of the radiopaque material concentration in a fixed length of the sutures at a selected time following surgical insertion and, using the previously developed relationship of radiopaque material concentration to suture elongation and suture failure, determine whether suture elongation has occurred and, if so, how close the sutures are to suture rupture elongation.

[0022] In another illustrative embodiment the suture material is subjected to stress tests in an environment similar to that which exists when in use. Wherever possible, the stress tests should be conducted under simulated in vivo conditions to account for any chemical embrittlement or dissolution effects. The stress-strain relationship of the suture from onset of elongation all the way to failure, including evaluation of the deformation by optical microscopy and scanning electron microscopy (SEM), can be accomplished. Pulling or stretching stress is applied to a suture specimen within an SEM, which allows a measurement of the suture diameter over a fixed length of suture and a calculation of the decrease in suture diameter over a fixed length of the suture at increasing increments of applied stress up until suture failure. This provides, for each suture tested, a relationship between the measured decrease in suture diameter at each increment of applied stress, including the unstressed or base line suture diameter (at zero percent decrease in suture diameter) and the failure diameter. Again, the physician is primarily concerned with the status of the repair sutures during the period between insertion and full healing. During that period in vivo visualizations of the suture diameter over a fixed length of suture are periodically made, for example, by X-ray, MRI, CAT scans, ultrasound, or other visualization technique which may be most appropriate and compared to the previously developed relationship of suture diameter to stress for the particular suture in use. If stretching of the suture occurs, then the diameter of the suture over the fixed length will diminish and the extent of any diameter decrease will be evident by comparing the diameter decrease corresponding to each periodically determined visualization to the base line suture diameter, to any previously measured suture diameter and to the suture rupture diameter to determine the condition of the suture relative to its base line and to its rupture condition at any time during the healing process. This information will allow a physician to determine whether the sutured repair is healing properly or is damaged and, if the latter, the seriousness of the damage. Alternatively, particularly where healing occurs over a shorter term, the physician may elect to make only one in vivo visualization of the suture diameter over a fixed length of the sutures at a selected time following surgical insertion and, using the previously developed relationship of suture diameter reduction to suture elongation and suture failure, determine whether suture elongation has occurred and, if so, how close the sutures are to suture rupture elongation.

[0023] Particularly for multifilament sutures which include a core and a sheath, as previously described, it may be informative to know whether the sheath is failing prior to the core and, if so, how much prior. This information can be determined, if it occurs, during the aforementioned stress tests using optical microscopy and SEM. If sheath failure prior to suture failure is noted, it is noteworthy at what radiopaque suture concentration or suture diameter reduction the sheath failure occurs. This will furnish the physician with still another data point to assist in determining the condition of the sutured repair relative to the anticipated time for complete healing of the repair. For example if, hypothetically, for a particular type and size of suture, it is known that sheath failure occurs very shortly prior to suture failure, then the physician will know that if sheath failure has occurred, then some medical or surgical intervention is likely warranted. Conversely, if, hypothetically, for a particular type and size of suture, it is known that sheath failure occurs well prior to suture failure, then sheath failure can be used as an indication of approximately how long before complete suture failure and, depending upon the time to complete healing, whether any medical or surgical intervention is warranted.

[0024] It should be appreciated that the goal of providing quantitative in vivo monitoring of the healing process following surgical repair by using the unique properties of radiopaque sutures is merely illustrated by the methods disclosed herein and is equally applicable to other radiopaque surgical repair devices. The ability to quantify the healing process is of great diagnostic importance in procedures like tendon repair, hernia repair and wherever monitoring of a long-duration healing process is necessary. It will provide timely alert of potential catastrophic failure of the surgical repair. To this end it will be seen that the goal is achieved by, where appropriate, characterizing the suture failure mechanism, determining the optimum or, at least, functional indicia of suture failure and the sensor or instrumentation best able to accurately provide the necessary data for assesing the various stages of suture degradation prior to failure. This information is vital to developing monitoring guidelines, in the nature of charts, tables, algorithms, and the like, including reliable sensing instrumentation, for the physician to use in assessing whether the sutured repair is healing properly or is damaged and, if the latter, the seriousness of the damage.

[0025] While the present invention has been described in terms of specific embodiments thereof, it will be understood that no limitations are intended to the details of construction or design other than as defined in the appended claims.