Abstract
The present disclosure provides a method and a kit for inducing growth or regeneration of a damaged nerve of a subject, or the treatment thereof by applying a clot of blood that is withdrawn from the subject. The blood that is withdrawn from the subject is introduced to a lumen of a nerve enveloping hollow element that envelopes the damaged portion of the nerve while controllably coagulating within the lumen to form a clot on the damaged portion of the nerve. The clot, while in physical contact with the damaged portion of the nerve, enhances the rehabilitation of the nerve and may partially or fully restore its functionality.
Claims
1. A kit for inducing growth or regenerating a damaged nerve portion of a subject, the kit comprising: a nerve enveloping hollow element having a lumen for enveloping said damaged nerve portion such that said portion resides in at least a portion of said lumen; one or more blood withdrawal devices for allowing withdrawal of blood from the subject; one or more blood collection receptacles for receiving the blood withdrawn from the subject; a coagulation assembly configured for permitting mixture of the withdrawn blood with one or more coagulation inducers for initiating coagulation process of the withdrawn blood; and an applicator for introducing the incomplete coagulated blood into said lumen.
2. The kit of claim 1, wherein the coagulation assembly comprises a volume for introducing the withdrawn blood, said volume is contactable with one or more coagulation agents or anti-anticoagulation agents.
3. The kit of claim 1, comprising one or more anti-coagulation agents for mixing with the withdrawn blood.
4. The kit of claim 1, comprising a film or sheet for placing over said damaged nerve portion for forming said nerve enveloping hollow element.
5. The kit of claim 1, wherein said nerve enveloping hollow element is a nerve guidance conduit.
6. The kit of claim 1, comprising securing elements for securing said damaged nerve portion to the nerve enveloping hollow element.
7. The kit of claim 1, for use in a method for treating, inducing growth, or regenerating a damaged nerve portion, the method comprising: (i) enveloping said damaged nerve portion with a nerve enveloping hollow element having a lumen such that said damaged nerve portion resides in said lumen; (ii) withdrawing whole blood from the subject; (iii) mixing the subject's blood with one or more coagulation inducers; (iv) prior to complete coagulation of the blood, introducing the blood with the coagulation agent into said lumen; and (v) permitting the blood to coagulate in said lumen.
8. A method for regenerating a nerve in or across a damaged nerve portion, comprising: fitting a nerve guidance conduit having a lumen to envelope said nerve portion to reside in said lumen; and introducing a mixture of whole blood withdrawn from the subject with one or more coagulating inducers into said lumen prior to its complete coagulation.
9. The method of claim 8, wherein said fitting comprises placing a film or sheet over said portion and enveloping said portion with said sheet to form said conduit.
10. A method for inducing growth of nerve fibers across a damaged nerve portion, comprising: fitting a nerve guidance conduit to envelope said nerve portion; and introducing a mixture of whole blood withdrawn from the subject with one or more coagulating inducers into said lumen prior to its complete coagulation.
11. The method of claim 8 or 10, wherein the damaged nerve portion comprises cut nerve fibers.
12. The method of claim 11, wherein said nerve portion includes two cut nerve stumps that are surgically joined or brought into proximity.
13. The method of claim 12, wherein said fitting comprises: placing a film or sheet over said portion and enveloping said portion with said sheet to form said conduit.
14. The method of claim 12, wherein said fitting comprises: introducing the two nerve stumps into said conduit, one from each end of the conduit; and bringing the two stumps into proximity to one another within said conduit.
15. The method of claim 14, wherein said bringing, comprises securing the two stumps within said conduit by suturing.
16. The method of claim 10, wherein said introducing comprises filling a portion of the conduit's lumen with the mixture such that it comes into contacts with said nerve portion.
17. The method of claim 16, wherein said nerve portion includes two cut nerve stumps and said introducing is carried out such that said mixture comes into tight contact with said stumps.
18. The method of claim 8 or 10, comprising at least one of: (i) saturating the blood, prior to said introducing, with an oxygen-rich gas; (ii) mixing the blood, prior to said introducing, with one or more autologous cells.
19. The method of claim 18, wherein said one or more autologous cells comprise Schwann cell.
20-32. (canceled)
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0170] In order to better understand the subject matter that is disclosed herein and to exemplify how it may be carried out in practice, embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which:
[0171] FIGS. 1A-1D are schematic illustrations exemplifying different stages of the method of inducing growth or regenerating a damaged or cut nerve according to aspects of the present disclosure.
[0172] FIGS. 2A-2C are schematic illustrations exemplifying different stages of the method of inducing growth or regenerating a damaged nerve according to an aspect of the present disclosure.
[0173] FIG. 3 is a schematic illustration exemplifying an embodiment of the method according to an aspect of the present disclosure.
[0174] FIG. 4 is a schematic illustration exemplifying an embodiment of the method according to an aspect of the present disclosure.
[0175] FIGS. 5A-5B show test results of treating cut nerve of rabbits with the method of the present disclosure in comparison to cut nerves of rabbits treated by a standard common method. FIG. 5A shows histograms of axon density in the medial portion of the nerve of the two tested groups; FIG. 5B shows cross sections of the medial portion of the nerve of the two tested groups.
DETAILED DESCRIPTION
[0176] Reference is being made to FIGS. 1A-1D, which are schematic illustrations exemplifying different stages of the method of inducing growth or regenerating a damaged or cut nerve according to aspects of the present disclosure. FIG. 1A shows a first and second stumps 102 and 104 of a cut nerve of a subject being treated. A sleeve 106, e.g. a nerve guidance conduit, is having a lumen 107 extends between first and second open ends 108 and 110 and is configured to receive each of the stumps 102/104 through a respective open end, whereby the sleeve 106 is fitted over the first and second stumps 102 and 104. In FIGS. 1A-1D and FIGS. 2A-2B, the sleeve is presented as transparent to permit view of the elements that would otherwise be concealed thereby, however it is to be noted that the sleeve can be made of materials that have any degree of transparency between full transparency and full opaque.
[0177] In FIG. 1A the nerve stumps 102/104 are being introduced via the first and the second open ends 108 and 110, respectively, and being secured, e.g. by suturing to portions of the sleeve that envelopes the stumps. FIG. 1B shows the stumps 102 and 104 within the sleeve 106 and secured in position by securing elements 112 such that a portion that includes the end of each of the stumps 103 and 105 is within the lumen of the sleeve 106 and each of the stumps extends beyond the respective opening.
[0178] As can be seen in FIG. 1C, a mixture 114 of whole blood, typically blood withdrawn from the subject, with one or more coagulation inducers, being one or more coagulating agents and/or one or more anti-anti coagulating agents, is introduced into the lumen 107, prior to the complete coagulation of the mixture, namely when the blood is still in a flowable state. The introduction of the mixture into the lumen can be performed by a syringe 109 or any suitable means. The lumen 107 is filled with the mixture such that the mixture contacts at least portions of each of the stumps. FIG. 1D shows that the mixture forms a continuous matrix linking the two stumps 102/104. The coagulation process of the mixture proceeds when it is within the lumen 107 until a clot is formed that contacts or envelopes one or two of the stumps 102/104. The sleeve 106 may be made to fit snugly over the nerve stump. However, in the event this is not the case, in order to retain the mixture within the lumen 107, the first and the second open ends 108 and 110 may be sealed, e.g. by a cloth, a dressing means, or any suitable sealing means.
[0179] Reference is now being made to FIGS. 2A-2C, which are schematic illustrations of a non-limiting example of an embodiment according to an aspect of the present disclosure. FIG. 2A shows a sleeve 206 that is fitted over a damaged portion 211 of a nerve NE of a subject. The sleeve may be formed by a sheet wrapped around the nerve NE; or may be formed from a flexible tubular element having an axially extending cut in its wall to permit it to be opened for placing over the nerve. Once the sleeve 206 is in place, a mixture 214 of whole blood, typically blood withdrawn from the subject, with one or more coagulation inducers, is introduced into a lumen 207 of the sleeve 206, prior to the complete coagulation of the mixture, namely when the blood is still in a flowable form, as can be seen in FIG. 2B. The mixture 214 fills the lumen 207 such that it contacts or envelopes the damaged portion 211 of the nerve NE and is maintained in the lumen to form a clot that contacts or envelopes the damaged portion 211 of the nerve NE, as can be seen in FIG. 2C. In time, the clot induces regeneration or growth of the damaged nerve.
[0180] FIG. 3 is a schematic illustration of a non-limiting example of an embodiment of the method according to an aspect of the present disclosure. In this example, the damaged nerve is a cut nerve having a first nerve stump 302 and a second nerve stump 304. The two stumps 302 and 304 are linked to each other via a nerve graft 320 having channels 322 that facilitate nerve growth therethrough. The channels 322 of the nerve graft 320 extending between a first end 324 and a second end 326 of the nerve graft 320. The first end 324 is joined with the first nerve stump 302 and the second end 326 is joined with the second nerve stump 304. A whole blood that, that is typically withdrawn from the subject that is being treated, is mixed with one or more coagulation inducers (namely, coagulation agents and/or anti-anti coagulation agents) to obtain a mixture 315 of whole blood with coagulation inducers, which is then being introduced, by an applicator 309, into the channels 322. The introduction may also be by placing one or both ends 324/326 in the mixture to permit entry of the mixture into the microchannels by capillary forces. The mixture 315 may optionally also be applied in the interfaces between the nerve graft 320 and each of the nerve stumps 302 and 304. The whole blood is then being coagulated in the channels and optional on the interfaces to form clots that enhances the growth of the nerve fibers between the two stumps through the microchannels.
[0181] FIG. 4 is a schematic illustration of a non-limiting example of an embodiment of the method according to an aspect of the present disclosure. This example differs from the one in FIG. 3 by enveloping the interfaces between each nerve stump and the nerve graft with a sleeve 406 and optionally securing each of the stumps to the sleeve 406 and/or the nerve graft 420. The lumen 407 of the sleeve 406 is filled with coagulating whole blood such that the channels 422 of the nerve graft 420 are fully or partially filled with the mixture of coagulation initiators and whole blood 415; and also the gap between the stumps 402 and 404 and the nerve graft 420 is filled with coagulating whole blood, which results in a continuous clot between the two stumps.
Test of the Method of the Present Invention on Rabbits
[0182] The method of the present disclosure has been tested on a rabbit. A 2.5 cm portion of the Tibial nerve of the rabbit was cut. A nerve guidance conduit was fitted over the two edges of the nerve stump and the gap spanned between them. The two edges were secured to the nerve guidance conduit by suturing. Autologous whole blood was withdrawn from the rabbit and was activated by mixing it with coagulation initiators to initiate blood coagulation. Then, the lumen of the nerve guidance conduit was filled with the activated whole blood of the rabbit to form a blood clot matrix within the lumen that links the two edges. The growth and regeneration status of the nerve of the rabbit was examined 4 months after. FIG. 5A presents histograms of the percentage of axons in a given area of the nerve after 4 months. The left bar of each histogram shows the findings in the proximal portion of the nerve and the right bar of each histogram shows the findings in the medial portion of the nerve. The group that is addressed as With ActiGrft represents the rabbit that was tested with the method of the present disclosure. In both portions, the proximal and the medial, more axons were found in the group that used the whole blood clot within the conduit than the group that did not.
[0183] FIG. 5B shows cross sections of the medial portion of the cut nerve after 4 months. The left cross section is the control group that did not use the method of the present disclosure, in which the conduit was left empty, and the right cross section is the tested group that used the method of the present disclosure, in which the conduit was filled with coagulated whole blood of the rabbit. The myelin was marked and as can be appreciated, the cross section of the tested group shows much greater axons density than the control group.
