Our goals are to engineer material systems to not only better understand how hMSCs receive information from their 3D microenvironment, but to exploit this knowledge to design better strategies for tissue regeneration and healing.
There are a limited number of options for clinical surgeons who are faced with reconstructing bone defects that result from congenital anomalies, trauma, infection, and oncologic resection. Current grafting techniques and materials each have their own limitations and drawbacks. For this reason, we are developing approaches to create improved bone grafting materials that will act as scaffolds to recruit cells from surrounding tissues and promote natural bone regeneration processes. Using a versatile and robust thiol-ene polymerization scheme developed in collaboration with the Bowman laboratories at CU, we synthesize 3-dimensional matrices containing simple cell adhesion mimics, enzymatically-degradable linkages, the presentation of localized osteogenic factors, and the introduction of miRNAs. Current research aims to better understand the mechanisms of hMSC motility and design material-based strategies to direct/promote migration and differentiation. We are also using dynamic microtopographies to promote differentiation and study mechanotransduction in cellular microenvironments.
Our group has a long-standing interest in cartilage regeneration, beginning with a decade of research on the design of PEG-based hydrolytically degradable materials for chondrocyte delivery. Our recent efforts focus on better understanding how material niches can be designed to promote the chondrogenic differentiation of hMSCs. TGF-b1 induces chondrogenic differentiation of hMSCs, but only when cells are cultured in the right context (e.g., pellet cultures). Thus, current efforts have identified TGF-b1-binding peptides and focus on affinity gel design to understand the influence of TGF-b1's local concentration and contextual presentation on encapsulated hMSC differentiation. Complementary to this work and through collaborations with our materials group, we are also exploring the role of cell morphology, local gel mechanics, and gel degradability on the differentiation of hMSCs and chondrocytes.