1. Combinational regenerative inductive effect of bio-adhesive hybrid hydrogels conjugated with hiPSC-derived myofibers and its derived EVs for volumetric muscle regeneration
- Author
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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, and Su Ryon Shin
- Subjects
Human induced pluripotent stem cells ,Extracellular vesicles ,Bio-adhesive hydrogel ,Muscle regeneration ,Volumetric muscle loss ,Materials of engineering and construction. Mechanics of materials ,TA401-492 ,Biology (General) ,QH301-705.5 - 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.
- Published
- 2025
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