Our research goal is to establish technologies for musculoskeletal tissue regeneration. By integrating concepts of biomaterials, biomechanics, tissue engineering, and cell biology, we develop cell-instructive biomaterials to systematically study how cells interact with their surrounding environment in regulating tissue pathophysiology, and apply these findings to engineer new regenerative therapies for treating traumatic injuries and diseases pertaining to the musculoskeletal system.
Cell-Instructive Biomaterials for Muscle Stem/Satellite Cell Manufacturing & Transplantation
Muscle stem cell transplantation is a promising strategy to treat skeletal muscle injuries and diseases, but a direct injection of cells results in poor donor cell survival, engraftment, and function of transplanted cells. Methods to maintain and expand therapeutically potent muscle stem cells ex vivo for clinical translation also remain a significant challenge. To this end, our research focuses on engineering cell-instructive biomaterial-based technologies to (1) facilitate the transplantation of muscle stem cells, (2) augment muscle regeneration in musculoskeletal injuries and diseases, and (3) systematically understand how muscle stem cells integrate biophysical & biochemical cues derived from their geometrically asymmetric niche to regulate their function.
Han, WM; Mohiuddin, M; Anderson, SE; García, AJ*; Jang, YC* “Co-delivery of Wnt7a and Muscle Stem Cells using Synthetic Bioadhesive Hydrogel Enhances Murine Muscle Regeneration and Cell Migration during Engraftment,” Acta Biomaterialia, 2019, 96, 243-252. *Co-PI. PMID: 31228633.
Han, WM; Anderson, SE; Mohiuddin, M; Barros, D; Nakhai, SA; Shin, E; Amaral, IF; Pêgo, AP; García, AJ*; Jang, YC* “Synthetic Matrix Enhances Transplanted Satellite Cell Engraftment in Dystrophic and Aged Skeletal Muscle with Comorbid Trauma,” Science Advances, 2018, 4:eaar4008. *Co-PI. PMID: 30116776.
Hierarchical Biomaterials for Musculoskeletal Soft Tissue Mechanobiology & Regeneration
Physical forces play an important role in regulating cell function. But how do cells process externally applied physical stimuli in mechanically dynamic musculoskeletal soft tissues? We have previously established how applied tissue level strain is transferred to the underlying cells and regulates early cell responses in fiber-reinforced soft tissues. However, systematic inquiries to define the multi-scale load transfer (tissue to cells) mechanisms are challenging in native tissues due to inherent heterogeneities in structure and composition. To this end, we are engineering native tissue-mimetic biomaterial platforms that enable decoupling of biophysical and biochemical parameters across multiple length scales to understand how the load is transferred from the tissue to the underlying cells in healthy and pathologic load-bearing tissues.
Han, WM∇; Heo, SJ∇; Driscoll, DP; Delucca, JF; McLeod, CM; Smith, LJ; Duncan, RL; Mauck, RL*; Elliott, DM* “Microstructural heterogeneity directs micromechanics and mechanobiology in native and engineered fibrocartilage”, Nature Materials, 2016, 15, 477-484. ∇Co-Authors. *Co-PI. PMID: 26726994.
Han, WM; Heo, SJ; Driscoll, TP; Mauck, RL; Smith, LJ; Elliott, DM “Macro to Micro-scale Strain Transfer in Fibrous Tissues is Heterogeneous and Tissue-Specific,” Biophysical Journal, 2013, 105, 807-817. PMID: 23931328.