UCLA

Photopolymerizable hydrogels derived from naturally occurring polymers have attracted significant interest in bone and cartilage tissue engineering due to their mechanical and chemical similarities to extracellular matrices, biodegradability spatial and temporal control of polymerization, and ability to be cured in situ through a minimally invasive procedure. While hydrogels are used for a number of soft tissue regeneration, few studies have investigated the use of a photopolymerizable injectable hydrogel for bone tissue engineering applications. The objective of this thesis is to synthesize a novel hybrid chitosan/collagen hybrid hydrogel characterize its mechanical and chemical properties, evaluate its biological effect and investigate the use of such hydrogels for sustained growth factor release. It was found that these chitosan collagen hybrid scaffolds exhibited extensive incorporation of collagen and proper collagen fibril formation throughout the hydrogel and that incorporation of these fibrils resulted in increased stiffness as compared with pure chitosan hydrogels. Furthermore, incorporation of collagen did not result in observable differences in gelation time but did increase resistance to lysozyme based degradation. When utilized as a 2D substrate, the hybrid hydrogel enhanced and encouraged cellular attachment, spreading, proliferation, and osteogenic differentiation of mouse bone marrow stromal cells as there was observed an upregulation in alkaline phosphatase (ALP) activity as well as increased mineralization. Similarly when cells were encapsulated within a 3D CSCol hydrogel matrix, mBMSCs spread on the surface of the hydrogel, proliferated and exhibited greater ALP activity and larger mineral deposits. In addition to use of CSCol hybrid hydrogels as 2D and 3D systems, it was proven that CS photopolymerizable hydrogels could be used for controlled growth factor release by co-encapsulating protein-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles. PLGA microparticles encapsulated within CS hydrogels exhibited controlled sustained release of a fluorescent bovine serum albumin protein conjugate. Collectively, this thesis provides the initial understandings of a photopolymerizable hybrid CSCol hydrogel as a potential injectable bone tissue engineering system.