Tissue homeostasis is maintained by a complex interplay between cells and their surrounding extracellular-matrix (ECM). A complex milieu of chemical signals, such as chemokines and cytokines, provide a variety of cues directing development, wound healing or disease progression. Likewise, the physical environment, such as stiffness and topography, can have a dramatic impact on cellular fate as well. Our goal is to engineer material systems to not only better understand how stem cells receive these biochemical and mechanical information from their microenvironment, but to exploit this knowledge to design better strategies for tissue regeneration and healing.
Current grafting techniques and materials to reconstruct bone defects that resulted from congenital anomalies, trauma, infection, and oncologic resection have major 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, we synthesize 3-dimensional matrices containing simple cell adhesion mimics, enzymatically-degradable linkages and the presentation of localized osteogenic factors. Current research aims to better understand the mechanisms of hMSC motility and design material-based strategies to direct/promote migration and differentiation.
Cartilage remains one of the most difficult tissues to regenerate and represents a persistent challenge in the field of regenerative medicine. Chondrocyte delivery/differentiation is a long-standing interest in our group and our recent efforts focus on hydrolytically degradable materials and covalent adaptable networks (CANs). These systems can be designed to spatially control chondrogenic differentiation of hMSCs and extracellular matrix (ECM) deposition by progenitor cells. Current techniques involve using biochemical cues such as tethered small molecules and mechanical cues to control cellular behavior.
Besides bio-chemical cues, mechanical cues have been reported to play a supremely important role in stem cell fate decision. However, the mechanism of mechanotransduction in stem cell is still elusive. So we are designing synthesized poly ethylene glycol (PEG) based hydrogel system with tunable mechanical properties to shed light on stem cell’s mechanosensing ability and mechanotransduction mechanism. On one hand, novel hydrogel systems with photo tunable mechanical properties have been designed to study spatially and temporarily mechanical dosing effects of stem cells. On the other hand, we are developing micro- and nano-hydrogel systems, to apply the fundamental studies into clinical engineering applications, such as tissue regeneration and other stem cell based therapies.