Collagen tubes for regenerating nerve
SUBSTANCE: collagen tubes can be used for connection and regeneration of damaged nerves. Tube is formed of single sheet of collagen-containing material. Sheet has smooth small-sized external barrier surface preventing connecting tissue from growing through it. Tube also has internal sift fibrous surface which helps nerve to grow at higher speed.
EFFECT: higher speed of regeneration of damaged nerves' prevention of scars.
18 cl, 4 att, 4 dwg
Cross-reference to related application
This application claims the effect of the provisional application ser. No. 60/214848 filed June 28, 2000
Prerequisites to the creation of inventions
The technical field of the invention
The present invention relates to the field of nerve regeneration.
Description of the prior art
It is known that damaged the nerves in some cases can be reunited using the methods of anabolically, according to which the ends of the nerves is inserted into a silicone tube, which may contain porous capable of dissolving the copolymer collagen-transplant-glycosaminoglycan (collagen-GAG or CG). Although this method has been used to connect the nerves, the application is unable to resorption of silicone tubing requires further surgery to remove the tubes.
In order to avoid secondary surgery to remove the silicone tubing used is capable of resorption tube of collagen type I tendon bull. Were made of a tube of collagen type I tendon bull with pore diameter of the side wall of approximately 22 nm (designated as "porous collagen") and pore diameter of the side wall of less than 3,8 nm (which is sometimes incorrectly referred to as "non-porous collagen"). These tubes of collagen type I tendon get on the Osia viscous gel of purified collagen type I on a rotating mandrel and extruding the material with the receipt of densely Packed fibers. Tubes are chemically cross-linked and liofilizirovannami. One of the disadvantages of using tubes, obtained from the above-described collagen type I tendon, is that connective tissue and fibroblasts can penetrate through the pores in the walls of the tubes of collagen type I tendon, which leads to the formation of scar tissue and prevents the reunification of the ends of the nerves. In addition, the internal surface of the tubes of collagen type I tendon obtained according to the method described above, can also prevent the reunification of the ends of the nerves.
Thus, in this area, there remains a need to develop improved methods and structures for regeneration and reunification of damaged nerves.
Summary of the invention
The object of the present invention is a tube for nerve regeneration with capable of resorption of the lateral wall, which consists of collagen, having a compact, smooth outer barrier surface that is designed to inhibit the adhesion of cells, and which acts as a barrier that prevents the penetration through her cells. The tube has a soft fibrous inner surface in contrast to the smooth barrier surface.
Brief description of drawings
Figure 1 schematically shows a view of the btes is the membrane, of which receive the tube in the first embodiment of implementation of the present invention.
Figure 2 schematically depicts the end view of the completed tube in the first embodiment of implementation of the present invention.
Figure 3 shows, partly schematically, a side view of the tube according to the first variant implementation of the present invention.
Figure 4 schematically depicts the end view of a tube obtained by blending the edges, according to the second variant of implementation of the present invention.
Detailed description of the invention
The present invention relates to a method and structure for reunification and regeneration of damaged nerves, such as the peripheral nerves of the spine. According to the present invention using a tube formed from capable of resorption of collagen, having a compact smooth outer barrier surface to prevent germination of connective tissue, which prevents the formation of scar tissue and allows you to easily perform the healing of damaged nerves.
The outer barrier surface of the tube according to the present invention inhibits the adhesion of cells and acts as a barrier to the passage through it of cells such as fibroblasts.
The side wall of the tube according to the invention has a soft fibrous HV the inner surface opposite the outer smooth barrier surface.
According to preferred variants of the implementation tube according to the invention consists of a mixture of collagen type III and collagen type I, for example, in which the content of collagen type III is about 1-10 wt.%, and the content of collagen type I - about 90-99 wt.%. According to a particularly preferred variant implementation in the tube according to the invention the content of collagen type III is about 1-5 wt.%, and the content of collagen type I - about 95-99 wt.%.
According to a preferred variant implementation of the side wall of the tube of the present invention is produced from a collagen membrane tissue of a bull, pig or other source of animal origin.
According to a preferred variant implementation membrane fabric is a peritoneal membrane fabric of young calves.
One of the acceptable according to the present invention, materials for producing tubes is Bio-Gide®supplied by the company Ed. Geistlich Söhne AG für Chemishe Industrie. Material Bio-Gide® and access is described in the patent US 5837278, which is included in the present description by reference.
Material Bio-Gide® includes about 1-5% of collagen type III and about 95-99% of collagen type I.
1 shows a sheet of collagen containing material intended to receive the tube of the present invention, having a to the compact smooth outer barrier surface 10 and a soft fibrous surface 12 in contrast to the smooth barrier surface 10.
Probably soft fibrous inner surface 12 in the tube for nerve regeneration according to the present invention facilitates the regeneration of the nerve.
Nerve regeneration can also be alleviated with the proposed growth-enhancing nerve filling material inside the tube for nerve regeneration according to the present invention. According to a preferred variant implementation of growth-enhancing nerve filler material consists of collagen type I, collagen type IV, or a mixture thereof. Most preferably the filler material consists of collagen fibers, with mainly longitudinal orientation relative to the tube axis. Figure 2 shows the end view of the tube 14 of the present invention, containing the filler material 16, which includes collagen thread with mainly longitudinal orientation relative to the tube 14.
According to a preferred variant implementation of the filler material 16 is a mixture of collagen type I and collagen type IV, most preferably in a mass ratio of 1:1.
The filler material 16 also contains other ingredients that enhance the growth of the nerve, such as growth factors nerve (e.g., laminin), growth factor nerve (NGF) or the like, or mixtures thereof.
According to the first variant implementation tube for nerve regeneration at present is in the invention is manufactured by the method involving the use of sheet described above collagen containing material, such Bio-Gide®and the manufacture of pipes of this sheet. According to the first variant implementation of the two opposite ends 18 and 20 of the sheet of material connected together, getting the tube 14, as shown in figure 3. Two opposite ends 18 and 20 can be joined together by any suitable method of manufacture of tubes, such as the use capable of dissolving suture material 22, as shown in figure 3, which is a biodegradable filament, for example, contains collagen, polylactide, polyglycolide or the like In an alternative embodiment, can be applied with acceptable medical point of view, an adhesive such as fibrin glue suspension of starch or collagen.
Returning to figure 2, it should be noted that growth-enhancing nerve filler material 16 may be injected into the tube 14 after the pipe 14.
Alternatively, reinforcing the growth of nerve material of the filler may be prepared and dried by freezing to the formation of collagen sponges, cut into round cylinders, the diameter of which is approximately equal to the inner diameter of the tube 14. Porous cylinder can then be compressed and introduced into the pipe after the pipe 14.
According to another variant implementation, the possible suspension growth-enhancing nerve filling material may be deposited on the fibrous surface 12 of the sheet of collagen containing material, as shown in figure 1, to manufacture the tube. Then the tube can be made by twisting the membrane sheet with a suspension of filler material, attached to the fibrous surface, so as to obtain a one-stage tube with a filling inside. The two side edges can be connected by means of a suture materials, adhesive or suspension of filler material, which may act as an adhesive.
According to a variant implementation, shown in figure 4. the edges 18' and 20' of the two opposite sides impose on each other, receiving tube 14'. Superimposed on each of the edges 18' and 20' can be connected together using a suture material or adhesive 24, as shown in figure 4. Alternatively, reinforcing the growth of nerve material can be used as an adhesive for connecting the opposite side edges and receiving tube.
When amplifying the growth of nerve material of the filler used in the form of suspension for filling a tube filled tube is dried by freezing for storage before use in surgery.
In contrast to the method of producing tubes according to the invention directly from the membrane material, such as Bio-Gide®, the side wall of the tube according to the present invention can be made from a suspension of collagen to obtain compactopen outer barrier surface and a soft fibrous inner surface in contrast to the smooth barrier surface, described above. The material can then be dried by freezing to produce tubes of the present invention. In the process of applying the ends of the nerve are inserted into the open ends 26 and 28 of the tube 14 of the present invention to facilitate the reunification of nerve endings.
The invention is illustrated by the following examples which are not intended to limit.
Tube with an inner diameter of approximately 0.5-5 mm and a length of about 10-100 mm made from membranes of type Bio-Gide®. The edges of the tubes connect with suture material or adhesive.
A gel-like mass of collagen type I get from pork skins, as follows. Pig skin is crushed to pieces, the maximum size of which is 1 cm3. Pork skins remove the water using a water-soluble organic solvent and the solvent allowed to evaporate. Dried pieces of pork skin degrease with a liquid hydrocarbon solvent. The liquid hydrocarbon solvent is removed and dry pieces of skin allow it to absorb water. Hydrated pieces leather handle 1H. the sodium hydroxide solution and washed. Pieces of skin treated with 0,04n. solution of hydrochloric acid and again washed. The thus treated material is shredded in a colloid mill to obtain a homogeneous liquid suspension, with the holding approximately 1.5% of collagen. The suspension is placed in a syringe for injection and obtained according to example 1 of the tube is filled with suspension. The filled tube is maintained at a temperature of -20°C for 24 h and dried by freezing for 72 h under a pressure below 1 mbar.
The filling material containing 50% collagen type I and 50% of type IV collagen, obtained as follows. The suspension containing 1.5% of collagen type I, is obtained from pork skin according to example 2. A commercially available type IV collagen is mixed with water in a mixer to obtain a 1.5%suspension. Suspension of collagen type I and collagen type IV are mixed in equal quantities. The mixed suspension is placed in a syringe for injection and obtained according to example 1 of the tube is filled with a mixture of suspensions. The tube is maintained at a temperature of -20°C for 24 h and dried by freezing for 72 h under a pressure below 1 mbar.
The suspension obtained according to example 2, or a mixed suspension obtained according to example 3, applied to the fibrous side of the sheet Bio-Gide® and the leaves are twisted, imposing lateral edges of the sheets to each other and thus concluding inside the suspension, while the connection edges of the sides at one stage. Filled in this way the tube is then incubated at a temperature of -20°C for 24 h and dried by freezing during the 72 h under a pressure below 1 mbar.
1. Tube for nerve regeneration and the reunification of its ends with capable of resorption of the lateral wall formed from a single sheet of collagen containing material, having a compact smooth outer barrier surface, which consequently inhibits the adhesion of cells and acts as a barrier that prevents the penetration through her cells, and, in addition, in contrast to compact smooth outer barrier surface of the sheet material has a soft fibrous inner surface, which is designed to ensure the regeneration of the nerve, and the lateral wall of the tube includes a mixture of 1-10% collagen type III and 90-99% of collagen type I, the tube has an inner diameter of approximately 0.5-5 mm and the opposite ends of which penetrate the nerves for reunification and regeneration.
2. The tube according to claim 1, where the mixture contains about 1-5% of collagen type III and 95-99% of collagen type I.
3. The tube according to claim 1 containing a filler material, which includes collagen type I, collagen type IV, or their mixture.
4. The tube according to claim 3, where the filling material comprises collagen fibers, with mainly longitudinal orientation relative to the tube wall.
5. The tube according to claim 3, where the filling material comprises a mixture of collagen type I and collagen type IV.
6. The tube according to claim 5, where the collagen type I and collagen IV filling material are in a mass ratio of approximately 1:1.
7. The tube according to claim 3, where the filler material further includes a growth factor nerve growth factor nerve or their mixture.
8. The tube according to claim 7, where the filling material contains laminin as a growth stimulator nerve.
9. The tube according to claim 1, where the side wall is made of tissue collagen membrane.
10. The tube according to claim 9, where the tissue membrane is a peritoneal tissue.
11. Tube for nerve regeneration according to claim 1, having a length of 10-100 mm
12. The method of producing tubes for nerve regeneration according to claim 1, providing
a) using a single sheet of collagen containing material comprising a mixture of 1-10% collagen type III and 90-99% of collagen type I, and the sheet has a compact smooth outer barrier surface, which consequently inhibits the adhesion of cells and acts as a barrier that prevents the penetration through her cells, and soft fibrous inner surface in contrast to the smooth outer barrier surface, and
b) the manufacture of this one piece of tube, which has a side wall with a compact smooth outer barrier surface, oriented outward, and the side wall has a soft fibrous inner surface, in contrast to the smooth outer barrier surface.
13. The method according to item 12, where does the t collagen containing material has two opposite lateral edges and two lateral edges of the sheet together, receiving from the tube sheet.
14. The method according to item 13, further comprising a stage of connection of the two side edges together with getting from the tube sheet.
15. The method according to item 12, in which the sheet is made up and additionally use the material to fill the tube, which includes collagen type I, collagen type IV, or their mixture.
16. The method according to item 12, in which the sheet has two opposite sides which are superimposed on each other with the receiving tube.
17. The method according to clause 16, in which the sheet is made up and additionally use the material to fill the tube, which includes collagen type I, collagen type IV, or their mixture.
SUBSTANCE: bone-and-mineral product contains porous bone mineral particles produced from natural bone and having crystalline structure practically corresponding to natural bone structure and practically containing no endogenous organic material. The particles have fibers of physiologically compatible type II resorbable collagen at least on their surface. Mass proportion of type II collagen fibers and porous bone mineral is at least equal to approximately 1:40.
EFFECT: enhanced effectiveness in recovering combined injuries of cartilage and bone tissue in articulations having defects.
8 cl, 6 dwg
SUBSTANCE: the present innovation deals with the method to accelerate mucosal healing due to the following technique: one should apply a membrane consisted of purified collagenic material obtained out of natural collagen-containing tissue onto the part of affected mucosa to provide the chance for mucosal reconstruction in this part and, also, it deals with mucosa-regenerating preparation and application of purified collagenic material obtained out of collagen-containing natural tissue for preparing mucosa-regenerating preparation. The innovation provides more modified method that accelerates mucosal regeneration, as a whole, and, particularly, after surgical operations associated with the plasty of oral fornix.
EFFECT: higher efficiency.
12 cl, 3 dwg, 5 ex
FIELD: medicine, ophthalmology.
SUBSTANCE: the present innovation deals with a drainage for treating glaucoma that includes collagen types II-III immobilized in polymer of acrylic and vinyl rows, includes a cytostatic covalently bound with collagen types II-III, hypotensive preparation and not less than one rigidity rib at certain ratio of components. The innovation provides improved ocular hydrodynamics, suppression of reparative and cicatricial processes around the drainage suggested.
EFFECT: higher efficiency.
6 dwg, 3 ex
SUBSTANCE: method involves introducing sharp tip of hollow needle into bone cortical layer crack. The crack is filled through needle lumen by introducing Collapan gel mixed with radiopaque substance in minimum concentration providing radio contrast range excess above injured bone contrast. Soft tissues are pierced with the needle in the vicinity of crack filling area center. Needle bevel plane is set in crack plane projection and introduced into the crack. Then, needle tube is rotated with its bevel plane directed into crack space. The cerebral covering soft tissues are pressed to bone along the crack path above positioned needle tip projection and the mixture is introduced in the amount equal to crack cavity region under pressed sift tissue. The needle end is pulled and directed towards the opposite crack region without removing it from the soft tissues and the region is also filled. Collapan introduction into crack fissure is carried out under X-ray optoelectronic transducer control.
EFFECT: enhanced effectiveness of treatment; reduced risk of postoperative complications.
SUBSTANCE: method involves applying hydroxyapatite collagen material plate so that plate size is selected to be by 5-8 mm greater than trepanation opening.
EFFECT: enhanced effectiveness in making plastic repair of maxillary sinus; excluded allergic responses.
FIELD: medicine, in particular bioactive complex for organogenesis.
SUBSTANCE: claimed complex represents multicomponent, bulk, three-dimensional structure, containing human allogene mesenchyme and epithelial cells and at least one layer of biocompatible polymer in form of collagen structure on network matrix. Biological complex of present invention is useful in regenerative and reparative reconstruction of any biological structures of mesemchyme-epothelial or mesodermal and ectodermal origin. Also disclosed are unified method for rebuilding of three-dimensional tissue defects and effective method for treatment of various gullet, urinary bladder parries, skin, gorge, eardrum, kidney, etc. defects. Complex also may be used in production of donor tissue equivalent bank.
EFFECT: active complexes for organogenesis useful in medicine.
3 ex, 1 dwg, 24 cl
FIELD: medical equipment.
SUBSTANCE: implant can be used for topographical positioning of tissues kept after wide resection of pathological parts. Implant has support frame made of sheet penetrable-porous titanium nikelide formed to be adequate to part of skeleton to be substituted, and supporting wire mesh made of titanium nikelide having super-elasticity effect; mesh is disposed at support frame at side of tissues to be supported. Supporting wire mesh is made according to textile technology of wire with diameter of 40-60 mcm to have distance between adjacent threads of 300-700 mc.
EFFECT: simplified design; reduced adjustment activities during operation.
2 cl, 7 dwg, 2 ex
FIELD: medical equipment.
SUBSTANCE: implant-carrier for surgical treatment of internal organs has member filled with cellular suspension. The member is made of porous titanium. Porosity of material is 20-70%, coefficient of penetration is 10-14-10-18 m2 and sizes of pores equal to 20-400 mcm.
EFFECT: prolonged service life of Implant; higher wettability of material; better biological compatibility of carrier's material.
2 dwg, 1 att
FIELD: medical engineering.
SUBSTANCE: device has stable-shaped warp-knitted film segment. The film is produced from biocompatible monothread including polypropylene threads. The film is integral knitted in width and formed by five or six longitudinal mesh columns of which three or four are external and two lateral ones connected by transverse underlaps lateral smooth rounded closed meshes. Mesh skeletons are formed by two threads in the internal columns, the outer columns being composed of meshes alternating over one mesh. The meshes have skeletons formed by two threads and one more thread due to two monothread systems being applied with knitting parameters like 1/0, 4/5 for the first system and 0/1, 1/0 for the second system with repeat being equal to 2. Polypropylene and/or polyvinylidene fluoride monothreads of diameter 0.8-0.15 mm are used.
EFFECT: reduced risk of traumatic complications.
2 cl, 1 dwg
SUBSTANCE: device has at least two porous polytetrafluoroethylene layers of different structure. The layer adjacent to parenchymal organ is composed of at least ten 30-120 mcm thick porous polytetrafluoroethylene layers having volume share of hollow space equal to 79-93%, specific surface of hollow space of 0.65-0.80 mcm2/mcm3, mean volume chord length of 25-30 mcm. The external layer has at least one 40-90 mcm thick porous polytetrafluoroethylene layer having 43-50% share of hollow space, 0.35-0.45 mcm2/mcm3 large specific surface of hollow space, mean distance between the bubbles in the volume being equal to 9,0-15,0 mcm, mean volume chord length of 8-11 mcm. General implant porosity is not less than 80%, implant thickness is equal to 1.0-2.0 mm.
EFFECT: producing implants allowing vasoselective parenchymatous sutures application.
6 cl, 5 dwg, 1 tbl
FIELD: medical devices, namely processes for forming coatings on surfaces of implants made of titanium in recrystallized or nano-structure state.
SUBSTANCE: coating contains, mass %: calcium titanate, 7 - 9; titanium pyrophosphate, 16 - 28; calcium phosphate compounds, the balance. Method comprises steps of anodizing implant by pulse electric current at condition of electric-spark discharge in phosphoric acid solution containing hydroxyapatite and calcium carbonate. Anodizing is realized by means of pulse current with next parameters: pulse time period, 50 - 200 ms; pulse repetition frequency 50 - 100 Hz; initial electric current density, 0.2 - 0.25 A/mm2; final voltage 100 -300 V. Invention allows to receive coating with thickness 40 - 80 micrometers.
EFFECT: possibility for forming coating whose composition is similar to that of osseous tissue with high content of calcium, improved osteoinductive and mechanical properties of coating.
7 cl, 3 ex
SUBSTANCE: method involves incubating transplants for preventing calcinosis occurrence in salt solution containing no calcium and phosphate ions but calcium chelators in the amount enough for initiating donor cells death and preventing calcinosis centers formation. Ethylene diamine tetraacetic acid is applied as chelator in 0.2-2.0% concentration or sodium citrate in 1-2.5% concentration. Digitonin is applied in concentration reaching 0.1% for increasing effectiveness and donor cells death. Incubation is carried out at salt solution pH being within the range of 5.0-7.5 and temperature from 10 to 37°C during 2-4 days.
EFFECT: enhanced effectiveness in preventing calcinosis and causing donor cells death; high transplant biocompatibility.
2 cl, 3 dwg
SUBSTANCE: the present innovation is directed to obtain a covering that provides high ability for developing bony tissue. This result should be fulfilled due to applying suspension upon titanium and its alloys with direct or impulse current under conditions of spark discharge, drying at about 80-120° C and roasting at about 600-800° C for 0.5-1 h, where as suspension one should apply synthetic and biological hydroxyapatite powder at the following quantitative ratio of components, weight%: synthetic hydroxyapatite powder 10-90, biological hydroxyapatite powder 10-90.
EFFECT: higher efficiency.
2 dwg, 3 ex, 1 tbl
FIELD: medical engineering.
SUBSTANCE: device has porous ceramic carrier layers and transverse bracing members, connected carcass having pores most of which have size from 20 to 1000 mcm and possessing density of 40% with respect to the theoretical one. Volume of the pores is optionally filled with a drug known to have controllable release rate from the filler.
EFFECT: enhanced effectiveness in providing controllable drug release rate from the filler.
30 cl, 3 dwg, 1 tbl
FIELD: medicine, plastic surgery.
SUBSTANCE: the suggested endoprosthesis is designed out of polymeric bioinert material and has a membrane, its surface is designed with protrusions as inclined cone-shaped, sharpened flexible projections. Direction, location at ends and interval between projections are made to be different depending upon target indication of endoprosthesis. Excessive ends of protrusions above the surface according to indication correspond to 0.01 up to 5 mm. The innovation enables to provide strong fixation of endoprosthesis in a patient's body.
EFFECT: higher efficiency.
7 cl, 12 dwg
FIELD: prosthesis techniques.
SUBSTANCE: invention, in particular, relates to cardiovascular surgery involving use of artificial mitral valves and also can be utilized in manufacture of implants of other organs in orthopedics, stomatology, traumatic surgery, and the like, as well as in various technical fields. Material of invention contains boron, silicon, and isotropic pyrocarbon in specified proportions.
EFFECT: increased strength, hardness, and wear resistance.
1 tbl, 3 ex
FIELD: medicinal equipment.
SUBSTANCE: the present innovation deals with means for restoring and/or keeping the lumen of blood vessel at treating cardio-vascular diseases due to implanting intravascular prostheses. The latter should be designed as a perforated cylindrical tube with grooves of patterned-cellular type which form at initial state periodically repeated rows of oval open rings connected with longitudinal and cross-sectional crosspieces. Repeated rows consist of the cells which in their initial state are of open oval rings the ends of which steadily come into cross-sectional crosspieces to unite these cells into the row. The second row of cells is developed due to mirror image of the first row being connected with the latter with longitudinal crosspieces. Next pairs of cellular rows are connected between each other with longitudinal crosspieces. By another variant for carrying out intravascular prosthesis, the second row of cells should be developed due to shifting the first row for the half of cellular width being connected with it by longitudinal crosspieces, as for the next cellular rows they are connected with longitudinal crosspieces. The method enables to improve flexibility of intravascular prosthesis at initial state and its rigidity at open state.
EFFECT: higher efficiency.
20 cl, 8 dwg