Designing cancer-inspired scaffolds for neural repair - Traumatic neural injury causes debilitating and permanent paralysis, in part because chronic inflammation
prevents the wound from healing. Our over-arching goal is to design biomaterial strategies for neural repair
that instruct remodeling of glial cells – important neural cells capable of regulating inflammation and tissue
regeneration. Glial cells become reactive after injury, propagating and maintaining the pro-inflammatory
environment leading to chronic inflammation. Recent studies have shown that these glial cells, namely
astrocytes and microglia, can adapt phenotypes for neuroprotection and repair given the right stimuli. In our
own work using a patient-designed model of brain cancer, we found introduction of glial cells to cancer cells
significantly alters glial cell reactivity. Cancer cells are known to express matrix proteins and cell-surface
glycans that train local cells, including glial cells, to adopt anti-inflammatory phenotypes. We hypothesize that
factors produced by cancer cells may inform design of new materials to retrain reactive glial cells to suppress
inflammation and promote repair after injury. To addressing these hypotheses, we will in this proposal 1)
characterize expression of extracellular matrix proteins and cell-surface glycans from several patient-derived
brain cancer cells, 2) from this characterization identify potential candidate molecules regulating glial cell
phenotype, and 3) screen for ligand combinations inducing anti-inflammatory glial phenotypes under normal
and inflamed conditions. This approach will leverage patient-derived glioblastoma cancer cells, two high
throughput biomaterial platforms, and programmable ligands for ‘click’ chemistry to establish the therapeutic
potential of using cancer to inform strategies for tissue regeneration. Ultimately, understanding how brain
cancer dictates behavior of neural cells, biasing them toward anti-inflammatory phenotypes, will enable
development of materials to instruct remodeling of the injury environment and promote repair, with possibly
widespread applications in a number of tissues and pathologies.