The design, manufacture and testing of a composite polysialic acid mimetic peptide loaded collagen nerve graft for use in peripheral nerve repair
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Date
2016-02-15Author
Doody, Jaime
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Abstract
Peripheral nerve injuries can be debilitating for patients. The current gold-standard technique for peripheral nerve repair is autograft. This procedure involves harvesting a non-critical nerve from a donor site from the same individual before using this autogenous neural tissue to repair the injured area. There are several disadvantages associated with this technique and outcomes vary. The field of biomedical engineering has yielded several alternatives to autograft, but none of which are ideal and very few of which have been carried over into clinical practice. The “ideal graft” would be inexpensive, easy to make, easy to handle, have low antigenicity, good biodegradability and promote neural regeneration better than autograft. Resaerch has shown that physical cues and biochemical cues play important roles in neural graft design. Collagen is an excellent substance for use as a grafting material. It is versatile. It has low antigenicity. It is also relatively inexpensive and has shown experimentally to be useful in nerve grafting. Polysialic acid (PSA) is a polypeptide that has been linked to peripheral nerve growth, maintenance and repair. It is a difficult substance to work with. Polysialic mimetic peptides have been shown to exert identical effects to native PSA in biological systems. In this project, a nerve graft was designed and manufactured to take advantage of the neural regenerative physical cues afforded by a collagen fibre packed nerve conduit and the chemical cues provided by a PSA mimetic. This conduit was tested in live subjects and was shown to perform as good as autograft across several difference morphometric criteria. In the course of this project, a novel method was developed for chemically modifying collagen, a notoriously inert substance.