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Theranostics, Published 2025-1-13 | doi:10.7150/thno.103677
3D bioprintable Mg2+-incorporated hydrogels tailored for regeneration of volumetric muscle loss
Moon Sung Kang1,*, Jeong Min Kim2,*, Hyo Jung Jo1,#, Hye Jin Heo3, Yun Hak Kim3,4,5,6, Kyung Min Park2,7, Dong-Wook Han1,8
1Department of Cogno-mechatronics Engineering, Pusan National University, Busan 46241, Republic of Korea.
2Department of Bioengineering and Nano-bioengineering, Incheon National University, Incheon 22012, Republic of Korea.
3Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
4Department of Biomedical Informatics, Pusan National University, Yangsan 50612, Republic of Korea.
5Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
6Periodontal Disease Signaling Network Research Center and Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea.
7Research Center for Bio Materials & Process Development, Incheon National University, Incheon 22012, Republic of Korea.
8Institute of Nano-Bio Convergence, Pusan National University, Busan 46241, Republic of Korea.
1Department of Cogno-mechatronics Engineering, Pusan National University, Busan 46241, Republic of Korea.
2Department of Bioengineering and Nano-bioengineering, Incheon National University, Incheon 22012, Republic of Korea.
3Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
4Department of Biomedical Informatics, Pusan National University, Yangsan 50612, Republic of Korea.
5Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
6Periodontal Disease Signaling Network Research Center and Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea.
7Research Center for Bio Materials & Process Development, Incheon National University, Incheon 22012, Republic of Korea.
8Institute of Nano-Bio Convergence, Pusan National University, Busan 46241, Republic of Korea.
* These authors contributed equally to this work.
# Current Address: Department of Mechanical and Industrial Engineering, Northeastern University, Boston, MA 02115, USA.
Corresponding authors: Kyung Min Park, Dong-Wook Han
Abstract
Rationale: Current therapeutic approaches for volumetric muscle loss (VML) face challenges owing to limited graft availability and insufficient bioactivity. Three-dimensional (3D) bioprinting has become an alternative technology for fabricating native tissue-mimetic grafts, allowing for tailored structures and complex designs.
Methods: We developed an Mg2+-incorporated bioink composed of thiolated gelatin (GtnSH) and maleimide-conjugated gelatin (GtnMI) decorated with magnesium peroxide (MgO2), referred to as a GtnSH/GtnMI/MgO2 bioink. We designed in situ crosslinking between GtnSH and GtnMI to prepare cytocompatible bioink for 3D bioprinting of muscle mimetics.
Results: The incorporated MgO2 particles provided oxygen supplementation and myogenic cues. In vitro assays demonstrated that C2C12 myoblasts encapsulated in the GtnSH/GtnMI/MgO2 bioink exhibited high viability, intrinsic proliferation rate, and increased expression of key myogenic markers. In vivo transplantation of the 3D bioprinted GtnSH/GtnMI/MgO2 constructs facilitated muscle mass restoration and M2 macrophage polarization. Additionally, they downregulate the activities of CD4+ and CD8+ lymphocytes, inducing a transition from the initial inflammatory to the restoration phase.
Conclusion: The GtnSH/GtnMI/MgO2 bioink is a potential therapeutic strategy for enhancing myogenesis and skeletal muscle tissue regeneration.
Methods: We developed an Mg2+-incorporated bioink composed of thiolated gelatin (GtnSH) and maleimide-conjugated gelatin (GtnMI) decorated with magnesium peroxide (MgO2), referred to as a GtnSH/GtnMI/MgO2 bioink. We designed in situ crosslinking between GtnSH and GtnMI to prepare cytocompatible bioink for 3D bioprinting of muscle mimetics.
Results: The incorporated MgO2 particles provided oxygen supplementation and myogenic cues. In vitro assays demonstrated that C2C12 myoblasts encapsulated in the GtnSH/GtnMI/MgO2 bioink exhibited high viability, intrinsic proliferation rate, and increased expression of key myogenic markers. In vivo transplantation of the 3D bioprinted GtnSH/GtnMI/MgO2 constructs facilitated muscle mass restoration and M2 macrophage polarization. Additionally, they downregulate the activities of CD4+ and CD8+ lymphocytes, inducing a transition from the initial inflammatory to the restoration phase.
Conclusion: The GtnSH/GtnMI/MgO2 bioink is a potential therapeutic strategy for enhancing myogenesis and skeletal muscle tissue regeneration.
논문정보
- Research article
- 2025년 01월 (BRIC 등록일 2025-02-13)
- 국내 연구진
- 바이오·의료융합 > 바이오소재
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