IgG diffusion through bioengineered materials for peripheral nerve regeneration

In successful nerve regeneration, sprouting axons from the proximal nerve stump traverse the injury site, and make new connections with target organs. Axons that fail to reach an appropriate end organ or fail to make a functional synapse will eventually undergo Wallerian degeneration. However, the incidence of recovery is highly variable, and the return of function is never complete. The use of synthetic nerve guidance channels show promises in improving the repair of injured human nerves, and the release of soluble bioactive agents like cytokines, may improve the degree and specificity of neural outgrowth [1]. The fibronectin (FN) guidance material has been already shown to promote axonal growth of sensory and other axons in rat spinal injuries in a way and to an extent not seen with any other non-graft implant to date. Ingrowth of new nerve tissue was dramatic in speed and content [2]. Also hyaluronan (HA) derivative HYAFF-11 (benzyl ester of Hyaluronic Acid) has been tested to be used for the bioartificial nerve guidance first of all because of its well documented biocompatibility and biodegradability and secondly because its particular physical-chemical properties make it processable in various three dimensional forms. Considering the role of the cytokine TGF-beta1 in scar formation and the potentially obtainable improved results in the repair of central and peripheral nervous system injuries with local delivery of neutralising antibody to the pro-fibrotic growth factor TGF-beta1, this study focuses mainly on the development of a new mathematical model to predict the diffusion of human antibody anti-TGF-beta1 through bioengineered membranes. In order to identify the model parameters, laboratory experiments have been set up, characterising the uptake and release of anti-TGF-beta1 to and from FN and HA synthetic nerve guidance channel