Abstract Traumatic muscle injuries associated with volumetric muscle loss (VML) are characterized by muscle loss beyond intrinsic regeneration capacity, leading to permanent functional impairment. Experimental therapies to augment muscle regeneration, such as cell injection, are limited by low cell transplantation capacity, whereas conventional engineered muscle tissue transplants lack geometric customization to conform to the shape of the muscle defect. Here, a facile approach to engineer scaffold‐free high‐density muscle tissues in customizable geometric shapes and sizes with high cell viability and integration potential is developed. Using a facile mold‐based approach to engineer scaffold‐free modular units, transcriptional profiling is performed to uncover the role of pre‐formed cell–cell interactions within scaffold‐free muscle bioconstructs on myogenesis, an the efficacy of muscle bioconstructs in a mouse model of VML is then evaluated. RNA sequencing revealed that pre‐formed cell–cell interactions supported myogenic pathways related to muscle contraction and myofibril assembly, unlike dissociated monodisperse cells. This work further demonstrates the therapeutic efficacy of 3D rectangular solid‐shaped scaffold‐free transplants in improving muscle function and vascular regeneration. Finally, toward clinical translation, the feasibility of this technology to integrate with medical imaging and artificial intelligence‐driven customized bioconstruct design and assembly for intraoperative use is illustrated.
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Advances in tissue engineering approaches for repairing and rehabilitating the myotendinous junction
The myotendinous junction (MTJ) acts as a bridge between muscle and tendon; yet its high stiffness relative to muscle fibers renders the tissue susceptible to injuries due to eccentric loading disparities. The limited regenerative capacity of MTJ tissue and potential for postsurgical scarring and reinjury necessitates complementary therapeutics that can enhance cellular interactions, restore mechanical properties, and support tissue rehabilitation. This review explores various approaches to engineer the MTJ utilizing biomaterial scaffolds and cellularized materials that mimic structure and function. While biomimetic materials show promise, challenges remain due to the interface’s complexity and differing patient- and location-specific structure–function characteristics, necessitating further research to address these gaps. This review also highlights the importance of studying MTJ injuries in women’s health and craniofacial reconstruction. Furthermore, engineered MTJ models provide versatile platforms for investigating trauma and degeneration, thus offering potential for advancing research across multiple fields, shedding light on interactions at tissue interfaces, and shaping the future of MTJ rehabilitation.
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- Award ID(s):
- 2236414
- PAR ID:
- 10520031
- Publisher / Repository:
- Elsevier
- Date Published:
- Journal Name:
- Current Opinion in Biomedical Engineering
- Volume:
- 30
- Issue:
- C
- ISSN:
- 2468-4511
- Page Range / eLocation ID:
- 100532
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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