Engineering fibrin matrices for enhanced vascularization and cell infiltration
Douglas, Alison McKissock
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Wound healing and revascularization of tissues at sites of injury are fundamental problems in the field of regenerative medicine. One promising approach to supporting vascularization is the use of fibrin polymers, the natural blood clotting protein, as an injectable biomaterial construct. Current fibrin matrices/sealants for wound healing applications use high concentrations of fibrinogen and thrombin, forming a dense matrix to facilitate stable clot formation. However, this limits the ability for endogenous cells to infiltrate the wound site for adequate tissue repair. The overall goal of this work is to design materials that are mechanically robust for ease of handling and clot stability, but allow for increased cell infiltration and tissue regeneration by modifying the fibrin network ultrastructure. This is achieved using colloidal assemblies of ultra low cross-linked poly(N-isopropylacrylamide) pNIPAm microgels (microgels), which we have shown can alter network architecture and mechanics. We hypothesized that by modifying microscale network structure we would enhance infiltrating cell motility, endogenous cell recruitment and angiogenesis, and tissue regeneration. Ultimately, it was shown that microgels enabled enhanced cell motility and infiltration in vitro, and in-growth of small diameter vessels in vivo. While, enabling larger vessel vascularization and multicellular processes involving collective cell migration still remain to be realized, this novel system represents a new method of modifying dense biomaterial systems for enhanced regenerative outcomes.