Bioinspired alterations of collagen-glycosaminoglycan scaffolds for tissue regeneration applications

Following injury, adult musculoskeletal wounds undergo a process of repair, the body's way of quickly closing an area of damage. Repair is characterized by the development of granulation tissue (scar) which lacks the structural and functional properties of the native tissue's extracellular matrix (ECM). Scar formation has been linked to the presence of inflammation, as injuries in environments with little inflammation (e.g. fetal) heal via regeneration, in which the synthesized matrix physiologically mirrors that of the tissue pre-injury. The limited ability of the adult body to regenerate these tissues following injury as well as resolve excessive inflammation associated with injury or material implantation, calls for strategies to enhance and support the restoration of these tissues to their natural state. Through the use of collagen-based extracellular matrix mimics, this thesis describes bioinspired scaffold compositions aimed at providing inherent cues to direct cellular behavior towards regeneration in vivo. Growth factors play a significant role in the overall health, function and phenotypic fate of cells in vivo and in vitro. We used charged glycosaminoglycans (found naturally in the ECM) to electrostatically sequester growth factors within the collagen matrix, preventing biomolecule degradation and presenting relevant factors to fibroblasts and mesenchymal stem cells. We showed that these glycosaminoglycans could also influence the three-dimensional delivery of charged-based gene vectors. While necessary to prevent infection during wound healing, inflammation, especially if it is prolonged, contributes to scar formation. By incorporating the anti-inflammatory matrix of the amniotic membrane into the collagen ECM analog, we sought to provide a biomaterial that would temper this inflammatory response to allow for tissue regeneration. This fetal environment-inspired material was studied in fibroblast, stem, and immune cell populations in vitro and in an in vivo animal model. Overall, this work demonstrates the effective modification of scaffold composition in order to address issues of transient growth factor sequestration, gene delivery capacity, or immunomodulation