Hyaluronic Acid Hydrogels with Sustained Growth Factor Release for Use in Conjunction with Intracerebral Hemorrhage Evacuation

Current clinical trials for hemorrhagic stroke use minimally invasive surgery plus tissue plasminogen activator for intracerebral hemorrhage evacuation (MISTIE). Evacuation by catheter provides a great opportunity to also inject a therapeutic. The goal is to transplant oligodendrocyte progenitor cells in a delivery system that will promote survival and differentiation. As a preliminary study using a new mouse model, the delivery system was adapted without cells and with bioactive signals to promote angiogenesis, which has been tied to the migration of endogenous neural stem cells, rather than differentiation. The delivery system consists of a hyaluronic acid hydrogel crosslinked by matrix metalloproteinase-sensitive peptides with adhesion peptides to promote cell infiltration. VEGF and PDGF-BB are encapsulated in a plasmin-sensitive peptide shell for sustained release of growth factors to promote angiogenesis. This was injected into mice following stroke and stroke evacuation similar to the MISTIE protocol. Analysis revealed difficulty working with the ICH model after stroke evacuation; stroke location was occasionally inconsistent, which may be partially due to the need for three separate injections for each mouse: stroke induction, stroke evacuation, and hydrogel injection. Because liquids are injected under pressure, a small difference in injection location can result in a significant difference in stroke or hydrogel location due to flow