박성수 (성균관대학교 기계공학부/바이오메디컬엔지니어링/양자생명물리학과) | 한빛사논문 > 한빛사

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성균관대학교 기계공학부/바이오메디컬엔지니어링/양자생명물리학과

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Adv. Funct. Mater., Jan 15 2024, 34 (3) 2304153 | https://doi.org/10.1002/adfm.202304153 Engineering Stem Cell Fate Controlling Biomaterials to Develop Muscle Connective Tissue Layered Myofibers

Seokgyu Han ^1,2, Myung Chul Lee ¹, Alejandra Rodríguez-delaRosa^3,4,5, Jiseong Kim ⁶, Margot Barroso-Zuppa ^1,7,8, Montserrat Pineda-Rosales ^1,9, Seong Soo Kim¹, Takaaki Hatanaka ^1,10, Iman K Yazdi ^11,12, Nicole Bassous ¹, Indranil Sinha ¹³, Olivier Pourquié ^3,4,5, Sungsu Park ², Su Ryon Shin ¹

¹Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.

²School of Mechanical Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea.

³Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.

⁴Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

⁵Harvard Stem Cell Institute, Harvard University, Boston, MA 02138, USA.

⁶Department of Medical Biotechnology, Dongguk University, 32 Dongguk-ro, Goyang 10326, Republic of Korea.

⁷School of Medicine and Health Sciences, Tecnologico de Monterrey, Mexico City 14380, Mexico.

⁸School of Medicine, Boston University, 72 East Concord Street, Boston, MA 02118, USA.

⁹School of Engineering and Science, Tecnologico de Monterrey, Santiago de Querétaro, Querétaro 76130, Mexico.

¹⁰Future Mobility Research Department, Toyota Research Institute North America, Toyota Motor North America Inc., Ann Arbor, MI 48105, USA.

¹¹School of Arts and Sciences, Regis College, Weston, MA 02493, USA.

¹²LiquiGlide Inc., Cambridge, MA 02139, USA.

¹³Division of Plastic Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

S.H. and M.C.L. contributed equally to this work.

CORRESPONDING AUTHORS : Sungsu Park, Su Ryon Shin

Abstract

Skeletal muscle connective tissue (MCT) surrounds myofiber bundles to provide structural support, produce force transduction from tendons, and regulate satellite cell differentiation during muscle regeneration. Engineered muscle tissue composed of myofibers layered within MCT has not yet been developed. Herein, a bioengineering strategy to create MCT-layered myofibers through the development of stem cell fate-controlling biomaterials that achieve both myogenesis and fibroblast differentiation in a locally controlled manner at the single construct is introduced. The reciprocal role of transforming growth factor-beta 1 (TGF- β1) and its inhibitor as well as 3D matrix stiffness to achieve co-differentiation of MCT fibroblasts and myofibers from a human-induced pluripotent stem cell (hiPSC)-derived paraxial mesoderm is studied. To avoid myogenic inhibition, TGF- β1 is conjugated on the gelatin-based hydrogel to control the fibroblasts' populations locally; the TGF- β1 degrades after 2 weeks, resulting in increased MCT-specific extracellular matrix (ECM) production. The locations of myofibers and fibroblasts are precisely controlled by using photolithography and co-axial wet spinning techniques, which results in the formation of MCT-layered functional myofibers in 3D constructs. This advanced engineering strategy is envisioned as a possible method for obtaining biomimetic human muscle grafts for various biomedical applications.

논문정보

형식Research article
게재일2024년 01월 (BRIC 등록일 2024-05-08)
연구진국내(교신)+국외 연구진
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