RESEARCH
We develop cell-instructive biomaterials to study mechanisms of stem cell-niche interactions, disease modeling, stem cell manufacturing, and stem cell therapy. Our long-term goal is to engineer translatable therapies for treating skeletal muscle trauma and diseases.
Bioengineering Strategies for Treating Rotator Cuff Muscle Disease
Rotator cuff tendon injuries are common and affect over 30% of the adult population. While surgical reattachment procedures are routinely performed, failure and re-tear rates remain high and worsen with aging. This is attributed to progressive degeneration of the associated muscles characterized by atrophy and intramuscular fatty infiltration, where fatty infiltration is caused by aberrant adipogenesis of the muscle-resident fibro-adipogenic progenitors. We recently determined that Wnt7a effectively suppresses the adipogenic potential of fibro-adipogenic progenitors through YAP/TAZ signaling. To this end, we are currently working to (1) unveil the roles of Wnt and mechanotransduction pathways in regulating fibro-adipogenic progenitor fates, and (2) develop hydrogel-based strategies for combating intramuscular fatty infiltration and atrophy in rotator cuff muscle disease in the context of aging.
Fu, C; Chin-Young, B; Park, G; Guzman-Seda, M; Laudier, D; Han, WM “WNT7a Suppresses Adipogenesis of Skeletal Muscle Mesenchymal Stem Cells and Fatty Infiltration Through the Alternative Wnt-Rho-YAP/TAZ Signaling Axis” Stem Cell Reports, 2023, 18(4): P999-1014.
Fu, C; Huang, AH; Galatz, LM; Han, WM “Cellular and Molecular Modulation of Rotator Cuff Muscle Pathophysiology” Journal of Orthopaedic Research, 2021, 39:2310-2322.
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, we are 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 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 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.
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Han Laboratory
Woojin Han, PhD
Assistant Professor
Department of Orthopaedics
Location
Lab: Annenberg A20-40
Office: Annenberg A20-66A
Contact
Phone: 212-241-4507
Email: woojin.han -at- mssm.edu
Twitter: @thewooj
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