A Novel Formulation For Non-Swelling Peg Hydrogels For Application In Spinal Cord Injury (SCI)

The notion of using hydrogels, which are 3-dimensional cross-linked polymer networks, for the delivery of biologically relevant molecules has been around for decades. However, with regard to administering hydrogels to anatomically sensitive areas like the spinal cord, there still exist 3 main challenges: the mechanical stress conferred by the swelling of the hydrogel, the rate of degradation of the gel network to control drug release, and the capacity of the hydrogel to maintain the efficacy of the drug over time.  In this project, all three areas are addressed. Testing of various novel formulations for PEG hydrogels has yielded a network that exhibits temperature-sensitive syneresis, which allows for complete control of swelling. In addition, specific additional modifications of the chemistry to alter the gel matrix’s susceptibility to hydrolysis has allowed for tailoring of the degradation of the hydrogel. As a result, precise tailoring of therapeutic drug release rate from the gel is attainable. Finally, the efficacy of incorporating stabilizing excipients into the gel network as a method of preserving the enzymatic activity of therapeutic proteins is being investigated and has shown tremendous preliminary potential. In particular, the incorporation of trehalose has been shown to confer stabilizing properties to the hydrogel as a whole with respect to the enzyme Chondroitinase ABC, which has therapeutic applications in spinal cord injuries.