Implant for injured nerve tissue regeneration and use of implant

Abstract

The invention relates to medicine and can be used in neurosurgery, traumatology, neurology, rehabilitation. The claimed invention is aimed to create the implant suitable for regeneration of injured nerve tissues of various types, in any period of the nerve tissue severe injury, in particular, of the spinal cord, immediately after relief of disturbed vital functions for the early and stable restoration of nerve tissue conduction in the acute period, prevention from or reduction of the demyelination processes. The implant is made of porous polytetrafluoroethylene (PTFE) with potentialities to maintain the histoenzymatic activity of neurons and restore the injured nerve tissue histostructure, such implant to contain at least a flat cylinder of 0.5 mm to 1. 5 mm high for placement in the injured nerve tissue area, with the flat cylinder's foot edges to contact undamaged nerve tissue areas, wherein the porous PTFE material has a three-dimensional structure containing open through pores and dead-end pores, evenly distributed over inner surface of the open through pores;, wherein the open through pores sizes and the dead-end pores sizes are randomly distributed within the range of 150-300 m.

Description

[0001] Implant for Injured Nerve Tissue Regeneration and Use of Implant

[0002] The invention relates to medicine and can be used in neurosurgery, traumatology, neurology, rehabilitation.

[0003] The known method of treatment for the sequelae of a traumatic injury to the spinal cord is to transplant intercostal nerves into the injured spinal cord [Yumashev G.S., Ziablov V.I., Korzh A.A. et al. / / Orthopedist, Traumatol. - 1989 - 1. P.71-74]. However, such method has a minor clinical effect. The axons in the central nervous system (“CNS”) appeared to be able to regenerate inside such implants, but unable to grow outside such implants, in order to restore connections with other CNS neurons; regenerating neurons “stick” inside the implant as a result of formation of a collagen scar.

[0004] There is one more known method of introduction of embryonal tissue bits between the central and peripheral ends of the injured spinal cord [Russian Patent No. 2195941, publication dd. 10 / 01 / 2003]. It cannot be considered sufficient, as the experimental studies have proven that with transplantation of an embryonal spinal cord fragment, the overlying axons grow out to the length of an implant, at the best, i.e. by 1 - 1.5 cm. The recipient axons do not grow more distally than the implant, they stick in the collagen scar.

[0005] Another known method of treatment for the sequelae of the spinal cord injury is to place the container, containing Schwann’s cells in the special gel, between the ends of the injured spinal cord. The Schwann’s cells obtained from explants of human or rat nerves are cultivated, and their amount increases significantly. Then the cells are placed in the matrix filling the semipermeable tubes, and they, in turn, place between the cut ends of the spinal cord. The result of most transplantations of Schwann’s cells is the regeneration of most CNS axons, their growing through the implant, however, the axons were unable to leave the microenvironment of the Schwann’s cells, in order to penetrate again in the depth of the spinal cord tissues and form new interneuron connections [Chinese Patent No. 101653366, publication dd. 24 / 02 / 2010].

[0006] Thus, the above-mentioned known methods may not be used for the effective restoration of the spinal cord function because the obstacles, i.e. collagen (connective-tissue) scar, cannot be overcome on the way of axon growth. Axons are unable to grow outside implants, in order to restore the connections with other CNS neurons; regenerating neurons “stick” inside the implant.

[0007] In addition, human tissue fragments were used as implants in the methods described, and this can result in both foreign body reaction and increased risk of the infection carry.

[0008] The implant and the method of treatment for spinal cord injuries under [U.S. Patent No. 7147647, publication dd. 12 / 12 / 2006] describing the implant as a porous titanium tube which inner and outer surface has one or several porous layers, with pore diameter of 1 - 3 pm and depth up to 0.5 pm, is the nearest Prior Art reference. The tube diameter depends on the diameter of the nerve subject to treatment.

[0009] The method of treatment is to place an injured nerve inside the claimed tube.

[0010] The disadvantage of this technical solution is the fact that the axon growth area is the porous layer of the inner surface of the tube only, thus, determining the limited number of nervous connections restored. Additionally, in order to be placed in the implant described, the injured nerve should be selected from the surrounding tissues, and this is infeasible for all areas of the human nerve tissue. In particular, the described implant is inapplicable to the spinal cord, as well as for other areas in any period of the severe injury immediately after relief of disturbed vital functions, which should contribute to the early and stable restoration of the spinal cord conduction in the acute period, prevent from or reduce the demyelination processes.

[0011] The nearest Prior Art reference is the implant according to [WO2021 / 087281, published 06.05.2021] made of porous material and shaped as an insert of irregular configuration or a tube for inserting the ends of the damaged nerve from its opposite ends.

[0012] In practice, due to the delicate, non-rigid structure of the nerve tissue, it can be difficult to place and hold the distal and proximal ends of the injured spinal cord in direct contact with the insert of irregular shape. It is even more difficult to insert the ends of the injured nerve, especially spinal cord, into the known tube. To be able to insert these ends, the tube diameter must exceed significantly the injured nerve diameter, while the nerve tissue must also contact directly the implant’s porous material, covering the injured area, for the nerve tissue to grow inside the porous material rather than to make a keloid scar, i.e. the tube size should be most close to the injured nerve diameter.

[0013] The claimed invention is aimed to create the implant suitable for regeneration of injured nerve tissues of various types, in any period of the nerve tissue severe injury, in particular, of the spinal cord, immediately after relief of disturbed vital functions for the early and stable restoration of nerve tissue conduction in the acute period, prevention from or reduction of the demyelination processes, as well as minimizing scarring and adhesions in the area of nerve tissue damage. The technical result enabling to solve this aim is to ensure the sustainable histoenzymatic activity of neurons and restoration of the injured nerve tissue histostructure.

[0014] The aim said is solved in a porous material implant for injured nerve tissue regeneration, by that the implant made of porous polytetrafluoroethylene with potentialities to maintain the histoenzymatic activity of neurons and restore the injured nerve tissue histostructure, such implant to contain at least a flat cylinder of 0.5 mm to 1. 5 mm high for placement in the injured nerve tissue area, with the flat cylinder’s foot edges to contact undamaged nerve tissue areas, wherein the porous PTFE material has a three-dimensional structure containing open through pores and dead-end pores, evenly distributed over inner surface of the open through pores and connected with the inner surfaces of the open through pores; , wherein the open through pores sizes and the dead-end pores sizes are randomly distributed within the range of 150-300 pm.

[0015] The implant is preferably equipped with a split coupling, with the flat cylinder placed in the center as its integral part, and the implant also can be provided with a locking element on top of the said split coupling, made as an additional elastic split coupling covering at least 270°.

[0016] The flat cylinder can be placed at an angle to the central axis of the coupling, ranging 30° to 90°.

[0017] The nerve tissue is preferably the acoustic nerve or the optic nerve or, most preferably, spinal cord tissue.

[0018] The set objective is further solved by use of the claimed implant to maintain the histoenzymatic activity of neurons and restore the injured nerve tissue histostructure. The activity of enzymes representing succinate dehydrogenase, acetylcholinesterase in neurons located caudal to the injured nerve tissue site may be lower compared to neurons at more cranial location, while the activity of lactate dehydrogenase may be compensatory higher in these areas.

[0019] This invention is shown as an example on the following non-restrictive drawings.

[0020] Figure 1 shows a schematic view of the first example of realization of the claimed implant;

[0021] Figure 2 provides a side view of the claimed implant according to Fig.1 ;

[0022] Figure 3 shows a schematic view of additional example of realization of implant according to Fig.l;

[0023] Figure 4 shows a schematic view of another example of realization claimed implant;

[0024] Figure 5 provides a side view of the claimed implant according to Fig.4;

[0025] Figure 6 shows a schematic view of the preferred example of realization of claimed implant;

[0026] Figure 7 shows a schematic view of the claimed implant’s locking element;

[0027] Figure 8 shows a schematic view of the preferred example of realization of the claimed implant assembly with the locking element;

[0028] Figure 9 shows a schematic view of one more example of realization of claimed implant ;

[0029] Figure 10 provides the claimed implant according to Fig 9 in cross-section;

[0030] Figures 11 to 13 represent images of spinal cord sections for Example 1;

[0031] Figures 14 to 17 represent images of spinal cord sections for Example 2.

[0032] Figure 18 represents activity of enzymes of carbohydrate-energy metabolism in motoneurons: Succinate dehydrogenase (SDH) (A) and lactate dehydrogenase (LDH) (B), expressed in units of optical density;

[0033] Figure 19 represents acetylcholinesterase (AChE) activity in motoneurones expressed in units of optical density.

[0034] The first example of realization of the claimed implant (Fig. 1-3) is made of porous polytetrafluoroethylene in the form of flat cylinder 1 of 0.5 mm to 1.5 mm high (h), with the flat cylinder’s foot size not less than the predetermined operated spinal cord diameter and not exceeding the diameter of the dura mater of the operated spinal cord, wherein the porous PTFE material has a three-dimensional structure containing open through pores and dead-end pores, evenly distributed over inner surface of the open through pores and connected with the inner surfaces of the open through pores, wherein pore sizes are randomly distributed within the range of 150-300 pm.

[0035] Another example of realization of the claimed implant is made of porous polytetrafluoroethylene in the form of split coupling 2 with flat cylinder 1 placed in the center. Split coupling 2 features two hollow cylinders 3 sized not less than the predetermined operated spinal cord diameter and not exceeding the diameter of the dura mater the operated spinal cord, made integral with flat cylinder 1 so that the generatrices of cylinders 3 coincide in the generatrix of flat cylinder 1 (Fig. 4-5). A cut is made along the generatrix of each hollow cylinder 3, and half of the foot circumference of each hollow cylinder 3 is separated from the flat cylinder 1, forming elastic wings 4.

[0036] One more preferred example of realization of the claimed implant is made of porous polytetrafluoroethylene in the form of split coupling 5 with flat cylinder 1 placed in the center. Coupling 5 features two hollow half-cylinders 6 sized not less than the predetermined operated spinal cord diameter and not exceeding the diameter of the dura mater of the operated spinal cord, made integral with flat cylinder 1 so that the generatrices of semi-cylinders 6 coincide in the generatrix of flat cylinder 1 (Fig. 6). This example of realization of the implant is equipped with locking element 7 (Fig. 7), made as an additional elastic split coupling covering at least 270° for placing on top of the specified split coupling 5 (Fig.8) /

[0037] Another example of realization of the claimed implant (Fig. 9, 10) is made of porous polytetrafluoroethylene in the form of split coupling 2 with flat cylinder 1 placed in the center. The flat cylinder can be placed at an angle a to the central axis of the coupling, where a ranging 30° to 90°.

[0038] The claimed implant can be manufactured, e.g., as described in [Belarus Patent No. 10325, publication dd. 28 / 02 / 2008]. The porous PTFE implant is made by mixing of raw material granules with pore-former (common salt) granules, compression of the mixture obtained, washout of common salt from the obtained porous blank and its further sintering. The complex structure of pores is caused, in such case, by the comminuted form of pore-former granules. The sizes of the dead-ended pores are determined by sizes of pore-former small-fraction grains and sizes of the open through pores - by sizes of pore-former large-fraction grains.

[0039] The implants claimed can be used for the surgical treatment for the spinal cord injury, for example, as follows.

[0040] The patient with the spinal cord injury is subjected to NMR tomography for the spinal cord. The localization and size of the spinal cord defect, presence of cysts and commissures are determined. On the basis of the data, the spinal cord implant of the target size and shape is selected from the pre-manufactured implant set, then sterilized and stored in the sterile packing. The implant porous structure may be saturated with drugs or nerve tissue growth stimulator.

[0041] The patient is then subjected to typical laminectomy in the lateral recumbent position; the dura mater is opened. Then, the meningomyelolysis is made with 3.5x magnification; the distal and proximal ends of the injured spinal cord area are exposed. The formed collagen (connectivetissue) scar is excised.

[0042] The prepared implant’s flat cylinder 1 is placed in such a way to fill the space between the ends of the patient’s injured spinal cord area.

[0043] In practice, due to the delicate, non-rigid structure of the nerve tissue, it can be difficult to place and hold the distal and proximal ends of the injured spinal cord in direct contact with the foots of flat cylinder 1.

[0044] To overcome this difficulty, the implant according to Fig. 3 has been developed, in which the implant according to the first example of realization (according to FIGs. 1-2) is provided with fixing elements 8 for attaching them to the dura mater, which prevents displacement of the claimed flat cylinder 1.

[0045] To overcome the difficulty, the implant is designed in other examples of realization. When using the implant according to Fig. 4, after preparing the wound field, elastic wings 4 of hollow cylinders 3 are bent upward (Fig. 5), and their lower parts are brought under the uninjured spinal cord areas, the spinal cord is placed inside hollow cylinders 3 by turning it so that flat cylinder 1 fills the space between the ends of the injured spinal cord section. Elastic wings 4 are released, and both spinal cord sections are fixed inside coupling 2.

[0046] When using the implant according to Fig. 6, after preparing the wound field, semi-cylinders 6 of coupling 5 are brought under the spinal cord sections, and the undamaged spinal cord sections are placed inside semi-cylinders 6 by turning so that flat cylinder 1 fills the space between the ends of the injured spinal cord section. Then, the edges of locking element 7 (Fig. 7) are moved apart, locking element 7 is installed on coupling 5 and, due to the elastic material, locking element 7 covers coupling 5 (Fig. 9) with the spinal cord inside and fixes it.

[0047] The operative wound is sutured layer-by-layer, tightly.

[0048] The claimed implant of any design can be used for surgical treatment of other major nerve injuries, such as acoustic or optic nerves.

[0049] The animal studies, as described in examples below, have been carried out, in order to check the workability and effectiveness of the inventions claimed.

[0050] Example 1

[0051] The experiment involved spinal cord injury in T9- 10 area. Complete transection was performed using a scalpel, followed by porous PTFE implant placement in the injured area (first example of the claimed implant (according Figs. Ito 3)). The complete restoration of lab animal’s motor activity was reported.

[0052] Upon the lab animal examination, no damage to the skin was detected, the integrity of the visible mucous membranes was not damaged, and no macroscopic inflammatory manifestations were revealed. The minipig moved freely in the cage. The feeding and drinking methods applied according to the age and needs of this type of animal. No obvious signs of spinal cord injury were detected.

[0053] The degree of neurological impairment was assessed using the Garcia scale (Garcia, J.H. Early reperfusion as a rationale from therapy in ischemic stroke. / J.H. Garcia / / Rev. Neurol. 1995. - Vol. 23, No. 123. - pp. 1067-1110). For the animal studied, practically no neurological impairment was found (17 points out of possible 18). Biological samples were obtained from a male minipig weighing 80 kg after 6 months following complete spinal cord transection and PTFE implant placement. The sampling was made in compliance with the principles of bioethics.

[0054] Histological preparations in the area of injury and implantation (Fig. 11 : A - contact area of granulation tissue (P) with spinal cord (CM); B-D - implant. Staining: hematoxylin-eosin (A, B), Nissl (C, D). Magnification: x40 (A), xlOO (B), x400 (C, D)) showed a mature gliomesodermal scar, formed mainly by connective tissue elements with inclusions of lymphocytes, where myelin nerve fibers were identified (Fig. 11 A). The growth of connective tissue was detected in the implant pores (Fig. 1 IB), with microvasculature vessels being generated (Figure 11). Nerve cells and microglial cells were visualized directly on the implant surface (Figure 1 ID).

[0055] On transverse sections of the spinal cord cranial to the area of injury (Fig.12: Staining: hematoxylin-eosin (A, B, D), Nissl (C). Magnification: x40 (A), xlOO (B,D), x400 (C)), the characteristic features of gray and white matter were clearly visible (Fig. 12A,B). Gray matter had the specific pattern of symmetrical butterfly wings and was located in the center of the slice. Both stalks of gray matter were connected by a bridge consisting of numerous unmyelinated fibers running in the gray matter, especially dorsal to the central canal. Gray matter consisted of neurocyte bodies, nerve fibers and neuroglia. The anterior horns contained numerous intact motor neurons (Fig.l2C). The posterior horns contained tufted neurocytes, located diffusely and receiving sensitive impulses from neurocytes of the spinal ganglia, as well as internal neurocytes that transmitted sensitive impulses from the spinal ganglia to the motor neurocytes of the anterior horns and to neighboring segments.

[0056] White matter was located on the spinal cord periphery and consisted of longitudinally oriented predominantly myelinated nerve fibers that formed posterior (ascending), anterior (descending) and lateral (both ascending and descending) cords, as well as glial elements. On the side of the injury, microcysts were observed among numerous myelinated axons (Fig. 12D), and diffusely located glial cells were also found to increase in this area.

[0057] Caudal to the injured area (Fig. 13: Staining: hematoxylin-eosin (A, B, D), Nissl (C). Magnification: x40 (A), xlOO (B,D), x400 (C)), a similar picture was observed: the spinal cord gray and white matter was clearly visible (Fig. 13 A, B). Gray matter had the pattern of symmetrical butterfly wings, located in the center of the slice and consisted of the bodies of neurocytes, nerve fibers and neuroglia. In the anterior horns, unmodified motor neurons were detected (Fig. 13C). The posterior horns contained small neurocytes.

[0058] White matter, consisting of myelinated nerve fibers and glial elements, was located on the spinal cord periphery. On the side of the injury, microcysts were observed among myelinated axons (Figure 13D), and diffusely located glial cells were also found to increase in this area. The number of microcysts and glia caudal to the area of injury is slightly greater than in more cranial regions.

[0059] Significant preservation of the spinal cord histostructure was observed at areas cranial and caudal to the injury. The connective tissue with glial elements was found to grow in implant pores.

[0060] Thus, when applying the implant for pig spinal cord injury, a significant restoration of the spinal cord structure in the injured area was observed, with a gliomesodermal scar being formed.

[0061] According to morphometric examination of the injured area, the spinal cord area was found to decrease significantly, as compared to more cranial and caudal sections (Fig. 1.5). There was also a more significant decrease in gray matter area in the section as compared to white matter. The gray matter to white matter ratio was 0.30, while more cranial and more caudal areas rated 0.42 and 0.35 respectively.

[0062] Example 2

[0063] The experiment involved spinal cord injury in T9- 10 area, made consecutively with two male minipigs. Complete transection was performed using a scalpel, followed by porous PTFE implant placement in the injured area (another example of realization of the claimed implant (according to Figs. 4, 5) and preferred example of realization (according to Figs. 6 to 8)).

[0064] The complete restoration of motor activity was observed in dynamics. The dynamics of body weight gain were normal.

[0065] The degree of neurological impairment was assessed using the Garcia scale (Garcia, J.H. Early reperfusion as a rationale from therapy in ischemic stroke. / J.H. Garcia / / Rev. Neurol. 1995. - Vol. 23, No. 123. - pp. 1067-1110). For the animal studied, practically no neurological impairment was found (18 points out of possible 18).

[0066] Following the dissection and sampling, the spinal cord integrity was reported, despite the complete transection manipulations. No macroscopically significant malformations or pathological changes were identified. No obvious signs of inflammatory processes were recorded.

[0067] Referring to microscopic picture, processes of the spinal cord structural integrity restoration were observed, accompanied by activation of the body’s defense systems.

[0068] Histological preparations in the injury and implant areas (Fig. 14: A - contact area of glio- mesodermal scar with the implant; B - germination of granulation tissue into implant pores. Staining: Nissl (A), hematoxylin-eosin (B). Magnification: x400 (A), xlOO (B)) showed a mature glio-mesodermal scar, formed mainly by connective tissue elements (Fig. 14A). A significant growth of connective tissue was detected in implant pores (Fig. 14B), with the formation of blood vessels of different sizes.

[0069] In transverse sections of the spinal cord cranial to the injured area, the characteristic features of gray and white matter were clearly visible. Gray matter featured the specific pattern of symmetrical butterfly wings and was located in the slice center. Gray matter consisted of neuron bodies, nerve fibers and glia.

[0070] The anterior horns contained a large number of motor neurons (Fig. 15 A). Among the numerous unmodified motor neurons (Fig. 15B), nerve cells with signs of chromatolysis were identified (Fig. 15C). The motor neurons of the anterior horns cranial to the injured area were small in size - 471 .82 pm2on average.

[0071] The posterior horns contained tufted neurocytes, located diffusely and receiving sensitive impulses from neurocytes of the spinal ganglia, as well as internal neurocytes, transmitting sensitive impulses from the spinal ganglia to the motor neurocytes of the anterior horns and to neighboring segments.

[0072] Caudal to the injured area, the spinal cord structure turned to preserve significantly: gray and white matter were clearly visible. Gray matter featured the specific pattern of symmetrical butterfly wings, located in the slice center and consisted of neuron bodies, nerve fibers and neuroglia. The cross-sectional area was found to be larger than in the injured area and in more cranial sections.

[0073] Unmodified motor neurons were detected in the anterior horns (Fig. 16: Staining: hematoxylin- eosin (A), Nissl (B). Magnification: xlOO (A), *400 (B)). The posterior horns contained small neurocytes. The sizes of motor neurons differed slightly from those in the injured area and averaged 751.63 pm2. Single nerve cells with destructive changes were also identified. The number of diffusely located glial cells was also reported to increase.

[0074] A histochemical study was performed to find out the activity of enzymes of carbohydrate and energy metabolism (succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH)) (Fig. 17: Succinate dehydrogenase (A, B) and lactate dehydrogenase (C, D) in anterior horn neurons of the pig spinal cord, cranial (A, C) and caudal (B, D) to the injured area. Method: Lloyd. Magnification: x400; fig.18 - Activity of enzymes of carbohydrate and energy metabolism in motor neurons: SDH (A) and LDH (B), expressed in optical density units. * - statistically significant differences (p < 0,05)), as well as the activity of acetylcholinesterase (AChE) as a marker of cholinergic neurons. Neuronal activity was studied in areas located in cranial and caudal directions to the injury and implantation area (fig.19 - Acetylcholinesterase (AChE) activity in motoneurones expressed in units of optical density. * - differences are statistically significant (p < 0.05)).

[0075] Following the injury and implantation, the spinal anterior horn motor neurons demonstrated a decreased SDH activity in the area caudal to the epicenter of the injury, as compared to more cranial sections (Fig. 17A,B). At the same time, a compensatory increase in LDH activity was observed (Fig. 17C,D), which indicated a restructured energy production in neurons to the glycolytic pathway of glucose oxidation.

[0076] AChE activity was also significantly lower in more caudal section of the spinal cord as compared to areas cranial to the injury epicenter. After implant placement in the area of complete spinal cord transection, the minipig spinal cord demonstrated a significant restoration of its histostructure with formation of a gliomesodermal scar in the injured area. Connective tissue with glial elements was reported to grow in the implant pores.

[0077] Caudal to the area of injury, significant preservation of the spinal cord histostructure was reported, although the histoenzymatic activity of motor neurons was impaired as compared to more cranial sections. Cranial to the area of injury, chromatolysis of some anterior horn neurons was observed in gray matter, and microcysts were found in white matter. However, the histoenzymatic activity of motor neurons was high. This evidences the unique approach and specific implantation material used, since no one had previously reported such experimental results.

[0078] No allergic, tumor or other pathologies were reported.

[0079] No significant pathological changes in the morphological picture were detected in the pig cerebral cortex and cerebellum after potentially fatal spinal cord injury and implant placement. Data shows no major changes occurring as a result of transneuronal degeneration after axonal transection in the periphery.

[0080] After six months, the artificial material implantation made it possible to preserve motor functions, which were fully realized in the vivarium conditions. The dynamics of the spinal cord recovery following its complete transection demonstrated the activation of the body’s defense systems.

[0081] Peculiarities of nervous tissue reorganization showed that six months period was not sufficient for complete spinal cord restoration after its complete transection in a minipig. However, no experimental study had yet been able to achieve the results presented in this study.

[0082] The study results allow us to consider the implantation material under study as safe and promising for use as a medical product.

[0083] The use of the invention claimed allows:

[0084] 1. To transplant in any period of the severe spinal injury promptly after the relief of disturbed vital functions, which contributes to the early and stable restoration of its conduction in the acute period, prevents from or reduces the demyelination processes. The restoration of the spinal cord function eliminates the harmful consequences of the prolonged inactive state, which is of high psycho-emotional and socio-economic importance for patients and their relatives.

[0085] 2. To mitigate the impact of disability caused by severe vertebral-cerebrospinal injury.

[0086] 3. To improve the quality of life of persons suffered from severe injuries of the spinal cord.

[0087] Thus, this invention provides for the injured nerve tissue regeneration in volume, and this fact, in turn, determines the suitability of the claimed implant for treatment of nerve tissue injuries of various types, in any period of the severe nerve tissue injury, in particular, spinal cord injury, promptly after the relief of disturbed vital functions for the early and stable restoration of its conduction in the acute period, prevention from or reduction of the demyelination processes as well as minimizing scarring and adhesions in the area of nerve tissue damage.

Claims

AMENDED CLAIMS received by the International Bureau on 24 October 2024 (24.10.2024)

1. Porous material implant for injured nerve tissue regeneration made of porous polytetrafluoroethylene in the form of a split coupling, characterized in that in the central part of the split coupling provided is a flat cylinder as an integral part for placement in the injured nerve tissue area with the flat cylinder’s foot edges to contact undamaged nerve tissue areas, wherein, a the split coupling having a diameter of no less than the diameter of the tissue to be operated on and the flat cylinder having the height of 0.5 mm to 1.5 mm.

2. Implant of Claim 1 , characterized in that the flat cylinder is placed at an angle to the central axis of the coupling, ranging 30° to 90°

3. Implant of Claim 1 , characterized in that the split coupling is made in the form of two hollow cylinders, wherein, the generatrices of the cylinders coincide in the generatrix of the flat cylinder placed in the central part of the coupling, and a cut is made along the generatrix of each hollow cylinder and a half of the foot circumference of each hollow cylinder is separated from the flat cylinder to form elastic wings.

4. Implant of Claim 1 , characterized in that the split coupling is made in the form of two hollow half-cylinders, wherein, the generatrices of the half-cylinders coincide in the generatrix of the flat cylinder placed in the central part of the coupling.

5. Implant of Claim 4, characterized in that the implant is equipped with a locking element on top of the said split coupling, made as an additional elastic split coupling covering at least 270°.

6. Implant of Claim 1 , characterized in that the nerve tissue represents a spinal cord tissue or acoustic nerve or optic nerve.

7. Use of the implant of Claim 1 to ensure the sustainable histoenzymatic activity of neurons and restoration of the injured nerve tissue histostructure.

8. Use of the implant of Claim 7, characteri z ed in that, the activity of enzymes representing succinate dehydrogenase, acetylcholinesterase in neurons located caudal to the injurednerve tissue site are lower compared to neurons at more cranial location, while the activity of lactate dehydrogenase may be compensatory higher in these areas.[0001][0002]STATEMENT UNDER ARTICLE 19(1)[0003]The amendments have been made since the prior art cited in the International Search Report contains the features present in the original Claims.[0004]The original claim 1 was amended and now includes the features «the flat cylinder placed in the center as its integral part» of the original dependent claim 2, as well as the feature «the split coupling having a diameter of no less than the diameter of the tissue to be operated on» the ground for the amendment can be found in paragraph 40 of page 3 of the original description.[0005]The original claim 2 was canceled.[0006]The original claim 3 was renumbered in 2.[0007]New claim 3 was added. Ground for amendment: lines 39-45 p.3 of the original description, and figures 4-5.[0008]New claims 4 was added. Grounds: lines 47-52 p.3 of the original description, and figure 6.[0009]The original claims 4, 5, 6, 7 were renumbered in 5, 6, 7, 8 accordingly.

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