The idea behind biomimetic matrices, such as pre-vascularized scaffolds, is to mimic the structural and biological processes during musculoskeletal tissue development and design functional biomimetic structures such as decellularized pre-vascularized osteonic structures which promote stable blood vessel formation in vivo throughout bone healing.
The poor healing capacity of soft tissues in general and soft tissue interfaces in particular motivates the need for a sustained therapeutic delivery system specifically tailored to address the unique problems of tissue repair. Due to the composition and complexity of tissues, the ideal system would recapitulate the microstructure of the native tissue while also providing biochemical cues throughout the repair process to direct cellular activity and tissue remodeling. To this end, our group designs tunable multifactorial and spatial delivery of biochemical factor for long-term tissue repair. We are particularly interested in interfacial tissue healing, such as the musculotendinous junction, and the innovative design is remised on nanofibrous matrices for tissue integration that sequester regional depots of biofactor-releasing microspheres to locally regulate cellular activity throughout interfacial tissue repair.
The immunomodulatory and regenerative features of mesenchymal stem cells are regulated in part by extracellular vesicle (EV)-mediated paracrine signaling. EVs are small membrane-enclosed particles that transport bioactive proteins, metabolites, and genetic materials inherited from a parent cell. EVs play a critical role in tissue repair and regeneration by inducing phenotypic and genotypic changes in recipient cells, and thus are a viable cell-free therapy to circumvent issues associated with cell-based therapies. However, a major challenge towards therapeutic utility of EVs is their heterogeneous composition which complicates the design, standardization, and targeted delivery of EVs. Thus, our goal is identifying the EV components that play a critical role throughout musculoskeletal healing and engineering EVs with tailored functional properties for targeted repair.