Combinational regenerative inductive effect of bio-adhesive hybrid hydrogels conjugated with hiPSC-derived myofibers and its derived EVs for volumetric muscle regeneration

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 <i>in-situ</i> 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 <i>in-situ</i> 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 <i>in vivo</i> murine volumetric muscle loss model.

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Journal
Bioactive Materials
Published
2024-10-14
DOI
https://doi.org/10.1016/j.bioactmat.2024.09.013
Citations
1
Primary Topic
Electrospun Nanofibers in Biomedical Applications
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article
Field-Weighted Citation Impact
0.17

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article

Combinational regenerative inductive effect of bio-adhesive hybrid hydrogels conjugated with hiPSC-derived myofibers and its derived EVs for volumetric muscle regeneration

Nebras Sobahi, Jae-I Moon, Ki‐Tae Kim, Jieun Jeon et al.
1 citations
Bioactive Materials
Electrospun Nanofibers in Biomedical Applications
0.17
article

Combinational regenerative inductive effect of bio-adhesive hybrid hydrogels conjugated with hiPSC-derived myofibers and its derived EVs for volumetric muscle regeneration

Nebras Sobahi, Jae-I Moon, Ki‐Tae Kim, Jieun Jeon, Yori Endo, Da‐Seul Kim, Nicole Bassous, Jae Seo Lee, Su Ryon Shin, Indranil Sinha, Mohammad Asif Hussain, Woo-Jin Kim, Abdulhameed F. Alkhateeb, Alejandra Rodríguez‐delaRosa, Mahmoud L. Nasr, Seung Gwa Park, Olivier Pourquié, Wenpeng Liu, Jiseong Kim, Myung Chul Lee, Seong-Soo Kim, Jeong Wook Seo, Soo-Hong Lee, Andrea Donaxi Madrigal‐Salazar, Hyeseon Lee, Mariana Carolina Lopez-Pacheco, Dilara Yilmaz Aykut
article en
1 citations

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 <i>in-situ</i> 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 <i>in-situ</i> 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 <i>in vivo</i> murine volumetric muscle loss model.

Bioactive MaterialsVol. 43
Brigham and Women's Hospital (US), Harvard University (US), Seoul National University (KR), King Abdulaziz University (SA), Dongguk University (KR), Massachusetts General Hospital (US), Mohammed Bin Rashid University of Medicine and Health Sciences (AE), Harvard Stem Cell Institute (US), Seoul National University Dental Hospital (KR), Pusan National University (KR), Korea Institute of Science and Technology (KR), Tecnológico de Monterrey (MX)
Foundation for the National Institutes of Health, American Heart Association, Ministry of Education, Ministry of Health and Welfare, Korea Health Industry Development Institute, National Research Foundation of Korea, King Abdulaziz University, National Institutes of Health, Deanship of Scientific Research, King Saud University
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Electrospun Nanofibers in Biomedical Applications
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