Our Approach: We use enzyme catalyzed monomer synthesis, condensation polymerization, controlled radical polymerization techniques and thiol-ene chemistry to produce innovative polymers with supramolecular functionality and tunable physiochemical and biological properties. Our current focus is on the development of new glycosylated (sugar) materials that may mimic key elements of normal glia-glia and glia-neuron cell interactions, the neural stem cell niche or regulate immune cell functions in CNS lesions. These materials can be formulated in various innovative ways to create nanoparticles, hydrogels and elastomers to be used as drug delivery carriers, cell transplantation vehicles or incorporated into neuroprostheses fabrication.
Why we need NEW Biomaterials in Glia Engineering Studies?: Most of the biomaterial matrices that are widely used in CNS studies are based on fibrotic and serum proteins (e.g. fibrin, collagen, gelatin, laminin etc.). However, CNS glia interact predominately through glycosylated molecules (e.g. hyaluronan, aggrecan, neurocan, brevican, versican, tenascins, polysialylated-neural cell adhesion molecule (PSA-NCAM) etc.) with stromal/fibrotic proteins limited to CNS vasculature. Therefore, we see a need for new synthetic glycan based biomaterials inspired by normal CNS cell interactions that may be used to: (i) improve cell transplantation outcomes – cell survival, localization, integration; (ii) guide grafted progenitor cell fate/maturation; and (iii) improve host perception of implants.
Our Approach: We use transgenic mouse embryonic stem cell (ESC) and neural progenitor cell (NPC) lines to derive glial cells for our transplantation studies and to perform in vitro cell culture studies of glia-biomaterial interactions. One such transgenic NPC line contains a Ribotag (hemagglutinin (HA) tag on ribosomal protein L22) allele to facilitate cell specific genetic evaluation of grafted cells from whole tissue in vivo as well as identification of NPC and their progeny by immunohistochemistry (using HA as a reporter). Below is a transplanted NPC (identified by HA reporter – red) that has been directed to differentiate into a mature astrocyte (GFAP – green) in vivo in the uninjured mouse brain (scale bar=10 µm).
With the help of collaborators we use Adeno-associated virus (AAV) to mediate sustained expression of molecular cues in neurons, glia or non-neural lesion core cells.