This application claims the benefit from the priorities of European patent applications EP 17170502.3 of May 10, 2017 and EP 17202460.6 of November 17, 2017; the entire of these applications is hereby incorporated by reference. BACKGROUND OF THE INVENTION

1. TECHNICAL FIELD

The invention relates to a method for the non-invasive fragmentation of residual biomaterial after bone augmentation and to a device, which is specifically adapted to said method.

2. BACKGROUND INFORMATION

Alveolar ridge reconstructions including vertical augmentations are challenging procedures in dental implantology and can be summarized as complex bone augmentations [1]. These techniques require a mechanical stabilization of the augmented area due to the lack of natural support by the bony wall of the alveolar ridge.

The material concept is a far more difficult area with various opinions and colliding points of view amongst specialists due to a controversial scientific data situation [2]. Current techniques vary amongst different clinics mostly depending on the surgical skills and the level of understanding for the biology of bone on the side of the treating surgeon. Gold standard is the autologous bone block [3]. While cancellous bone in sufficient volumes can only be obtained from distant donor regions, it is possible to harvest cortical bone blocks locally. Cortical bone cannot remain as living tissue transplant containing vital cells without blood supply. Massive cortical blocks are therefore subject to complete resorption and remodeling with an associated long time course of complete healing and risk of complications over several years. This results in high fracture risk of the blocks and hardly predictable resorption. Biomaterial blocks with interconnecting porous system, analogous to natural cancellous bone are an approach to address this issue. Mechanical stability and elasticity properties of appropriate materials must allow drilling and screwing for fixation at the site of augmentation. One group of the two material types in this category are natural, non- deproteinized, mineralized bone matrices of xenogenic or allogeneic origin (MBM) [2, 4- 8]. The other group consists of artificial blocks with interconnecting porous system made from various appropriate materials like chitosan, polycaprolactone, polyphosphates, and others, that are often tested in the field of in vitro tissue engineering in combination with cells and not a clinical standard today [9-13]. Resorption is incomplete in these matrices, contrary to autologous cancellous bone. New bone is formed in a shell like way along the existing trabeculae that become resorbed during this process until the new bone layer is stable and functional. This results in residual material underneath the newly formed bone. Well-documented human histologies showed this effect in allogeneic bone blocks [14-16]. Nissan at al. proved a percentage of 29% non-resorbed allogeneic matrix residues under the newly formed bony ingrowth after 6 months [15]. This result is different from autologous bone grafts that are in fact also non- vital but become remodeled fast. Spin-Neto et al. observed an advanced stage of remodeling and less or no residual graft material in autologous bone and a high rate of residual material with less advanced healing and multiple sites of necrotic bone in allogeneic grafts after 7 months (n=17 allogeneic and n=12 autologous) [16]. It must be presumed that the problem of residual biomaterial is true for other osteoconductive materials as well.

Shell techniques use only a thin shell of stiff material to stabilize a particulate graft that can consist of 100% autologous bone chips or a mesh graft containing particulate, resorbable biomaterial additionally to fill large volumes. This approach reduces the critical material issue to a thin shell that can be completely circumvented or removed crestally at the time of implantation [1, 17-23]. Shell techniques are surgically more difficult and therefore biomaterial blocks with interconnecting porous systems either of natural or artificial origin are more favorable if the problem of residual material could be solved. A solution for this problem could also become applicable to monophasic ceramics, polymers and other bone matrices with interconnecting porous system all bearing the same problem of residual material and the associated risk of early severe periimplantitis after prosthetic loading.

Said biomaterial blocks with interconnecting porous systems can include mentioned appropriate biomaterials and will be abbreviated BIPS (biomaterial blocks with interconnecting porous system).

Therefore, the problem underlying the present invention was to provide a non- invasive method to reduce or remove residual biomaterial after bone augmentation.

It is known from orthopedics that shock waves can be applied in various chronic bone and joint problems as a non-invasive physical therapy. Further experimental work shows an effect in bone that is the basis of the inventory idea of the presented method and device. Shock waves have been shown to result in micro-fractures in the cancellous bone trabeculae when applied there [24]. In this animal experiment 1500 shock wave pulses at 27.5 kV with a capacitance of 80 nF were applied at 1 Hz. Micro-fractures in the bone were shown in this study.

It is deduced from this observation that micro-fractures also occur within a biomaterial block with interconnecting porous system and that this aseptic micro-injury leads to a new healing process in the biomaterial area that results in a more complete resorption of residual biomaterial.

This problem has been solved according to this invention by fragmentation of the biomaterial after bone augmentation with the aid of shock waves.

BRIEF SUMMARY OF THE INVENTION

Therefore, the invention relates to a method for the non- invasive fragmentation of residual biomaterial after bone augmentation which comprises generating shock waves; applying said shock waves transdermal or intraorally; and

targeting said shock waves toward said residual biomaterial. Furthermore, the invention relates to a shock wave generator specifically adapted to said method. BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a coronal cut transection of the skull with the maxillary bone and a biomaterial block osseointegrated in the alveolar bone.

FIG. 2 shows a disrupted biomaterial block pieces that will be partly or totally resorbed during the bone healing process.

FIG. 3 shows an optimized result with no residual biomaterial left.

FIG. 4 shows an acoustic lens of a shock wave generator with an adaptor which allows to adjust the focal point /target area of the lens to the position of the target at the implantation site of the biomaterial.

FIG. 5 shows a focused and a radial applicator hand piece with respect and the resulting shock wave width and depth.

FIG. 6 shows schematic representations of three different hand-held shock wave applicators

(a) represents a hand-held shock wave applicator according to the state of the art

(b) represents a hand-held shock wave applicator according to the invention, wherein the shock wave emitting part of said device forms an angle of 25 degree with the rest of the device;

(c) represents a hand-held shock wave applicator according to the invention, wherein the shock wave emitting part of said device forms an angle of 90 degree with the rest of the device;

DETAILED DESCRIPTION OF THE INVENTION

The bone augmentation relates to those applied biomaterial blocks with interconnecting porous system as described above (BIPS).

The related biomaterial blocks are osteoconductive and thus support the bony ingrowth of newly formed bone into the matrix. The related biomaterial blocks (BIPS) are preferably mineralized bone matrices (MBM), including allogeneic or xenogeneic ones, artificial biomaterial with interconnecting porous system or said biomaterial blocks containing collagen or other proteins or other resorbable biomaterials, including ceramics like tricalcium phosphate and silicates, biopolymers selected from the group consisting of polycaprolactone, polylactides and polysilicates, or chitosan or sugar-polymers.

The related biomaterial blocks alternatively may be non-resorbable BIPSs, including ceramics like hydroxylapatite or xenogenic ceramics or non-resorbable material types of the above mentioned.

The related biomaterial blocks alternatively may be other biomaterials with

osteoconductive properties.

The described shock wave application relates to the application of this technology in urology known as Extracorporeal Shock Wave Lithotripsy (ESWL). Shock waves in ESWL have typically a broad frequency spectrum between 20 kHz and some MHz. Most energy is between 100 kHz and 1 MHz with a peak at 300 kHz. Shock waves are typically applied in pulsed dosing to allow a calculated energy application with less heat generation, e.g. US patent application US 2012/0215138 Al and US patents cited therein. The strong application of a short shock wave leads to mechanical disruption of stiff structures as urea stones and to cavitation effect associated with it. This leads to pressures between 30 and 150 MPa for 0.5-3 microseconds, after a rise time of around 10ns and a following decompression with a negative pressure peak of approximately -30 MPa over 2-20 microseconds. Pulse energies are in a range of 10 to 100 mJ and energy densities are between about 0.2 and 2.0 mJ/mm ² whereby energy density is defined as the amount of acoustical energy transmitted through an area of 1 mm ² per pulse.

Said pulses of Shockwaves are applied in fast repetition (short pulse Shockwave). Further embodiments of the present invention are the following methods, wherein: (A) said method is applied in dental implantology or orthopedic surgery after bone augmentation with biomaterials.

(B) said method is applied in orthopedic surgery after bone augmentation with biomaterials in the spin or the tibia head or after hip revision arthroplasty.

(C) said shock waves are applied in the form of pulsed shock waves.

(D) said shock waves are focused toward said residual biomaterial.

(E) said shock waves are applied with the aid of an appropriately angulated device to target the desired area of the alveolar crest intraorally, in particular wherein the angle between the head of the shock wave generator and the handle ranges between 25 and 90 degree.

(F) the residual biomaterial is osteoconductive with an interconnecting porous system and/or resorbable.

All shock wave devices hitherto known are not suitable for intraoral fragmentation of residual biomaterial after bone augmentation in dental implantology, since non-angulated, linear devices cannot be applied easily intraorally.

Accordingly, the invention also relates to an adapted shock wave generator, which focuses the shock wave on the residual biomaterial after bone augmentation in dental implantology with an angulated applicator appropriate for intraoral application.

The focus can be adjusted within the applicator technically by modifying the acoustic lens, or by using a fixed focus and optionally expandable spacer device that is attached to the applicator tip in order adjust it to the calculated distance to the tissue surface and a calculated focus depth thereby. Preferably the system according to the invention consists of a base station and an applicator hand piece.

The described treatment, of disrupting biomaterial implants to achieve better resorption, can be applied in orthopedic surgery in an analogous ways with the existing medical devices as described above. The main indications in orthopedic surgery incudes: tibia head fractures, fraktures of the vertebral body in spine surgery and osteoplasty of the femur in hip revision arthropasty and other arthroplasty.

Example 1

A Botiss bonebuilder allogeneic spongiosa block is selected respecting the blood group and possible other types to reduce the risk of host versus graft reactions. The block is implanted in a defect area in the jaws to achieve an appropriate bony bed for dental implants. The block is fixed with osteosynthesis screws or other appropriate fixation devices. It is even possible to use the dental implant itself as described as Giesenhagen ring technique.

After an appropriate bony healing period of 3 to 6 months, the following treatment is applied before implantation and prosthetic loading by opening the restoration to the oral cavity via the marginal sulcus.

Implantation is left out in this treatment path, if the implantation was already done simultaneously with the bone block implantation.

A Storz MP200 ESWL base station with 21 Hz and 5.0 bar pressure is applied using a Storz Falcon applicator hand piece. The Falcon hand piece is a radial applicator„pump gun" leading to a less focused but also less deep penetration of the shock waves with the advantage of a wide radial effect area (cp. Fig. 5 (a)). The transmission tip is placed extra- orally on the skin and pressed firmly onto the cheek of the buccal region for the waves to reach the target area in the upper jaw or pressed firmly onto the cheek in the mandibular region for the waves to reach the mandibular alveolar crest and the desired region there. The same can be applied in the front teeth region through the lips.

Example 2

As in Example 1 , but wherein the hand piece is replaced by a focused hand piece like the Storz Sepia hand piece "Sniper gun" (cp. Fig. 5 (b)). This allows more focused shock waves achieving a better depth by reducing/narrowing the effect area.

Example 3

As in Examples 1 or 2, wherein the base station is replaced by the Storz Duolith ST. Example 4

A big mobile urological ESWL unit like the Storz Modulith SLK or a stationary unit like the Storz Modulith SLX-F2 can also be applied in a similar manner by adjusting the patient accordingly to allow the applicator to reach the desired target region in the jaws.

It may be necessary to apply appropriate analgesia including a possible intubation narcosis.

Example 5

As in any of the Examples 1 to 4, but wherein the hand piece is applied at the tibia or the hip area or the spine and targeted to the region with biomaterial osteoplasty.

The results of the treatments of examples 1 to 4 are shown in the figures 1 to 3.

FIG. 1 shows a coronal cut transection of the skull with the maxillary bone (1) and a biomaterial block (2) osseointegrated in the alveolar bone. Shock waves can be applied transgingival (3) or transdermal (4) through the related spaces, from facial exterior site (5) or from the oral cavity (6). FIG. 2 shows the disrupted biomaterial block pieces (7) that will be partly or totally resorbed during the bone healing process.

FIG. 3 shows the optimized result with no residual biomaterial left.

FIG. 4 shows an acoustic lens (9) of a shock wave generator with an expandable distance holder (10), which allows the adjustment of the focal point (8) of the lens with the position of the target at the implantation site of the biomaterial (2). The shock waves (13) are focused (14, 15) by the lens (9). The expansion (11) may be effected by pressurizing the fluid within the distance holder (10) via the inlet valve (16). Therefore, the distance between the lens (9) and the tissue (12) can be adjusted, so that the focal point (8) of the shock wave coincidence with the location of the biomaterial (2).

FIG. 5 shows a focused (17) and a radial applicator (18) hand piece with respect and the resulting shock wave width (19) and depth (20).

FIG. 6 shows schematic representations of three different hand-held shock wave applicators:

(a) represents a linear hand- held shock wave applicator (17) according to the state of the art.

(b) represents an angular hand- held shock wave applicator (21) according to the invention, wherein the shock wave (13) emitting part (23) thereof forms an angle of 25 degree with the rest of the device;

(c) represents another angular hand-held shock wave applicator (22) according to the invention, wherein the shock wave (13) emitting part (23) thereof forms an angle of 90 degree with the rest of the device;

The invention is based on the principle that resorbable biomaterial pieces of small size in an area of active acute healing as generated by the application of shock waves leads to a resorption of such particles. REFERENCES

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