Hydrogel-grafted degradable nerve guides

Abstract

The present invention is directed to the compositions and methods of preparing hydrogel-grafted nerve guides for peripheral nerve regeneration. Particularly, the present invention describes the nerve guides and methods for preparation of hydrogel-grafted nerve guides with encapsulated neurotrophic factors and a nanofiber mesh lining the inner surface of the guide. The present invention also provides methods for peripheral nerve repair using these hydrogel-grafted nerve guides.

Description

RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application No.: 61 / 062,424, filed Jan. 25, 2008. The entire contents of the aforementioned application is hereby incorporated herein by reference.GOVERNMENT SUPPORT[0002]The following invention was supported at least in part by National Science Foundation DMR-0748340. Accordingly, the government has certain rights in the invention.BACKGROUND OF THE INVENTION[0003]Injuries to the peripheral nervous system can result in physical discontinuity of a peripheral nerve, leaving two uncoupled nerve ends. If the gap between these ends is relatively small (<20 mm), the nerve ends are surgically sutured together after which normal regenerative processes lead to eventual recovery in most cases. For larger gaps, the most successful solution currently available is the use of a sensory nerve autograft. Alongside the fact that even autografts are successful only 50% of the time, problems such as donor-site morbidi...

AI Technical Summary

Benefits of technology

[0032]FIG. 3 depicts the release profile of two nerve guide are prepared according to a procedure described in Example 1 with BSA as a model protein factor loaded in a 5% PVA-124k-98 hydrogel prepared under two different processing conditions. The first ...

Problems solved by technology

Injuries to the peripheral nervous system can result in physical discontinuity of a peripheral nerve, leaving two uncoupled nerve ends.

Alongside the fact that even autografts are successful only 50% of the time, problems such as donor-site morbidity and donor nerve shortage prompt the search for alternative methods for promoting peripheral nerve regeneration.

Problems with this approach include leakage of growth factors from the nerve guide and growth factor inactivation.

While continuous delivery devices such as osmotic pumps and silicone reservoirs have been used to overcome these problems, they also suffer from complications such as device failure and inflammation resulting from the non-degradable components.

Complications with these methods arise also, however, due to the fact that growth factor release cannot be controlled tightly; some growth factors may be toxic when delivered at a high local concentration.

Even further, a problem known as the “growth-factor oasis” effect has been observed in which high levels of growth factors within the nerve guide allow axons to regenerate into the nerve guide but not out, because the regenerating axons simply become fixed to the local maximum in the growth factor concentration profile.

The poor control of neurotrophic factor encapsulation and release has been the limiting factors to develop an efficient release system to fully harness the potential benefits of local sustained release of neurotrophic factors to improve PNS regeneration.

The complication is that a) loading neurotrophic factors with controlled dose and release kinetics has been difficult; b) growth factor loading involves organic solvent and harsh conditions, which will significantly decrease the bioactivities of the growth factors; c) it is difficult to adjust the total dose of growth factors and the nanofibers independently.

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