Hydrogel-grafted degradable nerve guides

a degradable, nerve guide technology, applied in the direction of prosthesis, paper/cardboard containers, synthetic resin layered products, etc., can solve the problems of physical discontinuity of a peripheral nerve, leakage of growth factors from the nerve guide, and two uncoupled nerve ends, etc., to achieve sustained release and low protein burst

Inactive Publication Date: 2011-05-26
THE JOHN HOPKINS UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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.
Eve...

Method used

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  • Hydrogel-grafted degradable nerve guides
  • Hydrogel-grafted degradable nerve guides
  • Hydrogel-grafted degradable nerve guides

Examples

Experimental program
Comparison scheme
Effect test

example 1

Preparation of a Nerve Guide

[0079]1) Cast a 10 cm2 film of 50:50 PCL / PCLEEP on top of a glass slide mold from a 12% wt solution in dichloromethane.

[0080]2) Dry the film under vacuum over night to remove residual solvent.

[0081]3) Place slide on a hot plate and heat the film to 100° C.

[0082]4) Add 1 ml of 1% PVA in water on top of the film.

[0083]5) Quench the film at −20° C. for 30 minutes.

[0084]6) Add 500 μL of 5% PVA containing 5 μg GDNF on top of the film.

[0085]7) Freeze the composite at −20° C. for 12 hours.

[0086]8) Cool at 25° C. for 30 minutes.

[0087]9) Freeze the composite at −20° C. for 2 hours.

[0088]10) Cool at 25° C. for 30 minutes.

[0089]11) Repeat steps 9 and 10 for a total of 12 cycles.

[0090]12) Freeze-dry the construct.

[0091]13) Place electrospun PCL nanofibers modified with laminin on top of the hydrogel layer.

[0092]14) Roll the construct into a tube with inner diameter of 3 mm and the hydrogel layer on the luminal side.

[0093]15) Seal the membrane with a trace quantity of...

example 2

Release Profile of Model Proteins from the Nerve Guide Construct

[0095]A nerve guide is prepared as described in Example 1 with bovine serum albumin

[0096](BSA) as a model protein factor loaded in a 5% PVA-83k-99 hydrogel construct into buffered saline at 37° C., gel was frozen at −2° C. for 72 hours, followed by 4 conventional freeze-thaw cycles. The release profile of BSA is shown in FIG. 2.

example 3

Process of Preparing a Double-Layered Hydrogel Nerve Guide

[0097]1) Repeat steps 1-8 as described in Example 1 with Gel A loaded onto the PCL membrane.

[0098]2) Independently prepare a 0.5 mm thick PVA hydrogel (Gel B) by replicating steps 6-11 as described in Example 1, with the sole modification of omitting the growth factor loading.

[0099]3) Add 50 μL of 5% PVA solution on top of Gel A, then lay Gel B on top of the solution.

[0100]4) Repeat steps 9 and 10 as described in Example 1 for a total of 4 cycles.

[0101]5) Continue with steps 12-16 as described in Example 1.

[0102]Other modifications can be used to modify the rate of release of proteins from the hydrogel. The addition of a protein-free top layer provides an additional diffusion barrier to incorporate time-delayed protein release. Blending PVA with other water-soluble small molecular weight polymers changes the hydrogel crystallinity. Changing the number of freeze-thaw cycles, or simply incubation for prolonged periods at sub-ze...

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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...

Claims

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Application Information

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IPC IPC(8): A61B17/00B32B37/14B32B38/00
CPCA61B17/1128Y10T156/1043A61L27/3878A61L27/48A61L27/52A61L27/54A61L27/56A61L27/58A61L2300/414A61L2300/602A61L2300/608A61L2400/12A61L2430/32A61F2/0063A61F2/02Y10T156/10A61L27/383
Inventor HOKE, AHMETLIM, SHAWN HWEI-INLIU, XINGYUMAO, HAI-QUAN
Owner THE JOHN HOPKINS UNIV SCHOOL OF MEDICINE
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