Michael Sofroniew, University of California Los Angeles, Los Angeles, USA

Axon regrowth guided by growth factor gradients released from hydrogel depots

Funded in: 2014, 2015, 2016


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Problem: The local environment inhibits injured nerve fibers to regrow across the lesion and does not provide growth promoting factors.

Target: Using diblock copolypeptide hydrogels (DCH), certain growth factors can be locally administered and guide axons across the damaged tissue.

Goal: Sustained local release of molecules stimulating nerve fibers to regrow beyond the SCI lesions.

 

An important goal for improving outcome after spinal cord injury (SCI) is to identify ways to enable the regrowth of injured nerve fibers across areas of tissue that is damaged and scarred. Various molecules have been identified that have the potential to stimulate and support the regrowth of nerve fibers in cell culture systems. However, for various reasons these molecules cannot simply be swallowed or injected into the blood, but instead would require local delivery into the injury sites in order to be effective and at the same time avoid unwanted side effects. In most cases, prolonged but temporary delivery would be needed. Clinically translatable methods for such delivery are lacking.

The goal is to develop a biomaterial that can easily and safely be injected into, and near, SCI lesions to provide depots for sustained local release of multiple molecules that manipulate local cells and stimulate nerve fibers to regrow into healthy tissue beyond the SCI lesions. For the studies diblock copolypeptide hydrogels (DCH) are used, which are fully synthetic biomaterials. The previous works of the team demonstrate that DCH are safe and can deliver molecules that exert predictable effects over sererval weeks time after injection into the brain or spinal cord. This project will build on these findings and use DCH injected after SCI to deliver different types of molecules to manipulate scar forming cells and support the regrowth of injured nerve fibers into, through and beyond SCI lesions into healthy tissue. Hopefully this approach using DCH biomaterials will not only provide a powerful tool for investigating and testing new molecules that may promote the regrowth of nerve fibers after SCI, but also, because DCH are fully synthetic biomaterials, that there may eventually be a potential for clinical translation of DCH for use in SCI.