UCLA

Tissue engineering aims to create functional constructs that replicate the natural structure and function of native tissues. One of the essential components of this process is scaffolds, which serve as physical frameworks to support cell attachment, growth, and organization while emulating the extracellular matrix (ECM). Despite significant advances, current scaffolds face challenges in replicating the complexity of native tissue architecture and functionality. This dissertation investigates the design, fabrication, and functionalization of biomimetic scaffolds to mimic the ECM and to regulate cellular behavior. Various materials including synthetic polymers, natural biomaterials, and hydrogels were studied to enhance cell viability, adhesion, proliferation, migration, and differentiation through microenvironment engineering for targeted tissue regeneration. Fibrous and porous scaffolds were fabricated using polycaprolactone (PCL) via electrospinning and bacterial cellulose (BC) through bacterial biosynthesis, respectively, mimicking native ECM architecture. To improve the biochemical properties of scaffolds, PCL scaffolds were chemically modified to improve hydrophilicity and degradation rates, enhancing cell adhesion and proliferation. Bacterial cellulose scaffolds were functionalized with antibodies and cellulase to promote cell attachment and controlled degradation. Periodontal ligament stem cells (PDLSCs) cultured on these scaffolds exhibited superior adhesion and proliferation, highlighting their potential in periodontal regeneration. The biophysical properties of scaffolds were explored using electrical stimulation during BC production, creating aligned fibers that directed the alignment and maturation of human skeletal muscle myoblasts (HSMMs), suggesting applications in muscle repair. Mechanotransduction studies were conducted with hyaluronic acid methacrylate (HAMA) hydrogels, where tuning scaffold stiffness regulated monocyte/macrophage differentiation. Hydrogels promoted preosteoclast differentiation while inhibiting osteoclast fusion, presenting a novel therapeutic approach for osteoporosis. This study demonstrates how scaffold architecture and material properties significantly influence cell behaviors and tissue regeneration. The findings offer a systematic framework for designing advanced scaffolds, emphasizing material selection, fabrication techniques, and functionalization strategies. These insights advance biomaterial research and lay the groundwork for innovative regenerative therapies in periodontal regeneration, muscle repair, and osteoporosis treatment.