Bioactive Materials (Jan 2025)
Combinational regenerative inductive effect of bio-adhesive hybrid hydrogels conjugated with hiPSC-derived myofibers and its derived EVs for volumetric muscle regeneration
- Jiseong Kim,
- Myung Chul Lee,
- Jieun Jeon,
- Alejandra Rodríguez-delaRosa,
- Yori Endo,
- Da-Seul Kim,
- Andrea Donaxi Madrigal-Salazar,
- Jeong Wook Seo,
- Hyeseon Lee,
- Ki-Tae Kim,
- Jae-I Moon,
- Seung Gwa Park,
- Mariana Carolina Lopez-Pacheco,
- Abdulhameed F. Alkhateeb,
- Nebras Sobahi,
- Nicole Bassous,
- Wenpeng Liu,
- Jae Seo Lee,
- Seongsoo Kim,
- Dilara Yilmaz Aykut,
- Mahmoud Lotfi Nasr,
- Mohammad Asif Hussain,
- Soo-Hong Lee,
- Woo-Jin Kim,
- Olivier Pourquié,
- Indranil Sinha,
- Su Ryon Shin
Affiliations
- Jiseong Kim
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA; Department of Medical Biotechnology, Dongguk University, 32 Dongguk-ro, Goyang, 10326, Republic of Korea
- Myung Chul Lee
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA; Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
- Jieun Jeon
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA; Department of Medical Biotechnology, Dongguk University, 32 Dongguk-ro, Goyang, 10326, Republic of Korea
- Alejandra Rodríguez-delaRosa
- Department of Pathology, Brigham and Women's Hospital, Boston, MA, 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA; Harvard Stem Cell Institute, Harvard University, Boston, MA, 02138, USA
- Yori Endo
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA
- Da-Seul Kim
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA
- Andrea Donaxi Madrigal-Salazar
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA; Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias, Campus Guadalajara, Av. Gral. Ramón Corona No 2514, Colonia Nuevo México, Zapopan, Jalisco, 45121, Mexico
- Jeong Wook Seo
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA
- Hyeseon Lee
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA; Department of Biomaterials Science (BK21 Four Program), Life and Industry Convergence Institute, Pusan National University, Miryang, 50463, Republic of Korea
- Ki-Tae Kim
- Department of Molecular Genetics & Dental Pharmacology, School of Dentistry and Dental Research Institute, Dental Multi-omics Center, Seoul National University, Seoul, 03080, Republic of Korea; Epigenetic Regulation of Aged Skeleto-Muscular System Laboratory, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, 08826, Republic of Korea
- Jae-I Moon
- Department of Molecular Genetics & Dental Pharmacology, School of Dentistry and Dental Research Institute, Dental Multi-omics Center, Seoul National University, Seoul, 03080, Republic of Korea; Epigenetic Regulation of Aged Skeleto-Muscular System Laboratory, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, 08826, Republic of Korea
- Seung Gwa Park
- Department of Molecular Genetics & Dental Pharmacology, School of Dentistry and Dental Research Institute, Dental Multi-omics Center, Seoul National University, Seoul, 03080, Republic of Korea; Epigenetic Regulation of Aged Skeleto-Muscular System Laboratory, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, 08826, Republic of Korea
- Mariana Carolina Lopez-Pacheco
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA; Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias, Campus Guadalajara, Av. Gral. Ramón Corona No 2514, Colonia Nuevo México, Zapopan, Jalisco, 45121, Mexico
- Abdulhameed F. Alkhateeb
- Department of Electrical and Computer Engineering, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
- Nebras Sobahi
- Department of Electrical and Computer Engineering, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
- Nicole Bassous
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA
- Wenpeng Liu
- Division of Engineering in Medicine and Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA
- Jae Seo Lee
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA; Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital, Cambridge, MA, 02139, USA
- Seongsoo Kim
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA
- Dilara Yilmaz Aykut
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA
- Mahmoud Lotfi Nasr
- Division of Engineering in Medicine and Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA; College of Medicine, Mohamed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
- Mohammad Asif Hussain
- Department of Electrical and Computer Engineering, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
- Soo-Hong Lee
- Department of Medical Biotechnology, Dongguk University, 32 Dongguk-ro, Goyang, 10326, Republic of Korea
- Woo-Jin Kim
- Department of Molecular Genetics & Dental Pharmacology, School of Dentistry and Dental Research Institute, Dental Multi-omics Center, Seoul National University, Seoul, 03080, Republic of Korea; Epigenetic Regulation of Aged Skeleto-Muscular System Laboratory, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, 08826, Republic of Korea
- Olivier Pourquié
- Department of Pathology, Brigham and Women's Hospital, Boston, MA, 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA; Harvard Stem Cell Institute, Harvard University, Boston, MA, 02138, USA
- Indranil Sinha
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA; Corresponding author.
- Su Ryon Shin
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA; Corresponding author.
- Journal volume & issue
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Vol. 43
pp. 579 – 602
Abstract
In regenerative medicine, extracellular vesicles (EVs) possess the potential to repair injured cells by delivering modulatory factors. However, the therapeutic effect of EVs in large-scale tissue defects, which are subject to prolonged timelines for tissue architecture and functional restoration, remains poorly understood. In this study, we introduce EVs and cell-tethering hybrid hydrogels composed of tyramine-conjugated gelatin (GelTA) that can be in-situ crosslinked with EVs derived from human induced pluripotent stem cell-derived myofibers (hiPSC-myofibers) and hiPSC-muscle precursor cells. This hybrid hydrogel sustains the release of EVs and provides a beneficial nano-topography and mechanical properties for creating a favorable extracellular matrix. Secreted EVs from the hiPSC-myofibers contain specific microRNAs, potentially improving myogenesis and angiogenesis. Herein, we demonstrate increased myogenic markers and fusion/differentiation indexes through the combinatory effects of EVs and integrin-mediated adhesions in the 3D matrix. Furthermore, we observe a unique impact of EVs, which aid in maintaining the viability and phenotype of myofibers under harsh environments. The hybrid hydrogel in-situ crosslinked with hiPSCs and EVs is facilely used to fabricate large-scale muscle constructs by the stacking of micro-patterned hydrogel domains. Later, we confirmed a combinational effect, whereby muscle tissue regeneration and functional restoration were improved, via an in vivo murine volumetric muscle loss model.
