(489b) Engineered Microenvironment for Osteogenic Differentiation of Stem Cells

Bone is one of the most common transplanted tissues, second only to blood. Currently, autografts and allografts are the primary choice for treating compromised bone tissue, but both suffer from drawbacks such as donor site morbidity, scarcity, immunorejection, and disease transmission. In contrast, synthetic bone grafts with intrinsic osteoinductivity and osteoconductivity could provide an easy-to-manufacture and cost-effective therapeutic strategy for treating bone defects. However, employing biomaterial-based bone grafts to accelerate regeneration of critical bone defects requires a detailed understanding of bone extracellular matrix (ECM), its role in the differentiation of stem cells into osteoblasts, and tissue homeostasis. Recently, we have developed novel, synthetic bone-like ECM structures using principles of biomineralization. Thus-formed biomineralized matrices recapitulate various attributes of native bone ECM. Our ongoing studies involving human mesenchymal stem cells indicate that the biomimetic matrix directed their osteogenic differentiation both in vitro and in vivo. Furthermore, we have employed the biomineralized matrices as an “artificial niche” to understand the mechanism by which mineralized matrices induces osteogenic differentiation commitment of stem cells.