sPatially and environmentAlly aCtuable nancoMposite hydrogels towArds Nervous system repair

Ziel

This proposal aims to capitalize on my unique multi-disciplinary expertise in nanotechnology, tissue engineering, polymer/inorganic hybrids, and microsurgical techniques, while acquiring new proficiencies in the creation of breakable hybrid organosilica nanocapsules, mesoporous silica nanoparticles, and nanocomposite hydrogels. I am driven to tackle the unmet needs, opportunities, and challenges in the fields of nanocomposite hydrogel design and nervous system repair by combing my current expertise with these new proficiencies to innovate nanocomposite hydrogels that are environmentally and spatially actuable. Specifically, the goal of my proposal is to pioneer spatially distinct and environmentally responsive actuation of nanocomposite hydrogels in response to matrix metalloproteinase-9 (MMP-9) peptide cleavage, focusing on applications in peripheral nerve repair. In order to achieve this ambitious objective, I will develop MMP-9 degradable polyethylene glycol (PEG)/mesoporous silica nanoparticle composites and MMP-9 breakable organosilica nanocapsules through the incorporation of MMP-9 cleavable peptides into silica nanoparticle structures. MMP-9 can therefore be used to induce: 1) hydrogel degradation, 2) release of encapsulated therapeutics, and 3) capture of molecules by cleaved nanoparticle scavengers. This proposal details a highly interdisciplinary approach to create a plug-and-play nanocomposite hydrogel system to overcome obstacles needed to improve regeneration outcomes by combining neuroscience and microsurgical nerve repair with chemistry, drug delivery, biomaterials science, and tissue engineering. Finally, nanocomposite nerve guidance conduits will be tested in a peripheral nerve injury model to demonstrate in vivo MMP-9 actuation of these hydrogels.