MULTIFUNCTIONAL BIOACTIVE POLYMERS FOR THE FABRICATION OF TISSUE ENGINEERING SCAFFOLDS AND THE TREATMENT OF TISSUE ISCHEMIA BY

Tissue engineering has strived to address the need for viable tissue and organ sources to treat various diseases, including ischemic disease. Many of the advances in tissue engineering have focused on providing new scaffolds, which may incorporate cells and proteins, to control tissue regeneration and growth. However, further advancement of tissue engineering suffers from increasingly complex applications, which require the independent control of the physical properties of hydrogel scaffolds. Also, the need to increase the size of engineered tissues and treat ischemic diseases requires new methods to improve blood vessel growth. Therefore, the overall goal of this thesis is to develop advanced strategies for the design of hydrogel scaffolds which can tune the physical properties of hydrogels and improve revascularization therapies. This thesis describes the development of advanced biomaterials for refined cell culture, encapsulation, and neovascularization, including: polymeric cross-linkers which tunes the elastic modulus and swelling ratio of hydrogels in a more independent manner (Chapter 2); fibronectin or fibronectin fragments in fibrin gels to improve neovascularization (Chapter 3); alginate-sulfate to improve the efficacy of VEGF-mediated angiogenesis (Chapter 4); and a multi-functional hyperbranched polymer to guide transplanted stem cells to an ischemic tissue (Chapter 5). I propose that the biomaterial systems developed in this study should be readily translated into various clinical treatments for neovascularization. Ultimately, the results of this thesis study will greatly contribute to expediting the use of tissue engineering technology of various injuries, traumas, and diseases. ii