Hyaluronic acid hydrogel biomaterials for soft tissue engineering applications
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The primary focus of this work was to develop new naturally derived hydrogel scaffolds for soft tissue engineering applications such as peripheral nerve repair. Ideal implants for soft tissues are degradable, porous, highly permeable, able to maintain a desired shape, and able to specifically modulate biological responses. Naturally derived materials are particularly suitable for these applications because they are degradable and intrinsically bioactive. As presented in this dissertation, we have made significant steps towards meeting these aims by creating new hydrogel scaffolds from crosslinked hyaluronic acid (HA). As a biomaterial candidate, HA presents a unique combination of advantages. Specifically, HA is a naturally derived, enzymatically degradable, non-immunogenic, non-adhesive, bioactive glycosaminoglycan that has been associated with several cellular processes, including angiogenesis, extracellular matrix homeostasis, and the regulation of inflammation. In our first studies, we developed a novel hydrogel tissue engineering scaffold from photocrosslinkable glycidyl methacrylate-modified HA (GMHA). The GMHA hydrogels were found to be enzymatically degradable, biocompatible, and the degradation products of GMHA retained a similar level of bioactivity as unmodified HA fragments. Further development of these GMHA hydrogels focused on methods to attach peptides (e.g., the fibronectin-derived cell adhesion sequence RGD or arg-gly-asp). Such sequences could provide a versatile method to control several adhesion-related cellular processes, including migration and proliferation. Finally, we explored GMHA-based hydrogels for controlled protein release. Localized delivery of bioactive proteins such as growth factors provides an additional level of versatility for modulating specific cellular behaviors involved in tissue repair. We believe that these novel GMHA-based biomaterials offer unique advantages over synthetic and non-degradable scaffolding biomaterials and provide a solid foundation for further modification and use in a variety of soft tissue engineering applications.