Pelvic floor muscle function recovery using biofabricated tissue constructs with neuromuscular junctions
| Autor: | Anthony Atala, Margaret Maria Vanschaayk, Ji Hyun Kim, In Kap Ko, Ickhee Kim, Myung Jae Jeon, James J. Yoo |
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| Rok vydání: | 2020 |
| Předmět: |
0206 medical engineering
Muscle Fibers Skeletal Biomedical Engineering Neuromuscular Junction 02 engineering and technology Biochemistry Pelvic Floor Muscle Neuromuscular junction Biomaterials In vivo medicine Animals Function recovery Agrin Muscle Skeletal Molecular Biology Acetylcholine receptor Pelvic floor business.industry Skeletal muscle General Medicine Pelvic Floor Recovery of Function 021001 nanoscience & nanotechnology 020601 biomedical engineering Cell biology Rats medicine.anatomical_structure 0210 nano-technology business Biotechnology |
| Zdroj: | Acta biomaterialia. 121 |
| ISSN: | 1878-7568 |
| Popis: | Damages in pelvic floor muscles often cause dysfunction of the entire pelvic urogenital system, which is clinically challenging. A bioengineered skeletal muscle construct that mimics structural and functional characteristics of native skeletal muscle could provide a therapeutic option to restore normal muscle function. However, most of the current bioengineered muscle constructs are unable to provide timely innervation necessary for successful grafting and functional recovery. We previously have demonstrated that post-synaptic acetylcholine receptors (AChR) clusters can be pre-formed on cultured skeletal muscle myofibers with agrin treatment and suggested that implantation of AChR clusters containing myofibers could accelerate innervation and recovery of muscle function. In this study, we develop a 3-dimensional (3D) bioprinted human skeletal muscle construct, consisting of multi-layers bundles with aligned and AChR clusters pre-formed human myofibers, and investigate the effect of pre-formed AChR clusters in bioprinted skeletal muscle constructs and innervation efficiency in vivo. Agrin treatment successfully pre-formed functional AChR clusters on the bioprinted muscle constructs in vitro that increased neuromuscular junction (NMJ) formation in vivo in a transposed nerve implantation model in rats. In a rat model of pelvic floor muscle injury, implantation of skeletal muscle constructs containing the pre-formed AChR clusters resulted in functional muscle reconstruction with accelerated construct innervation. This approach may provide a therapeutic solution to the many challenges associated with pelvic floor reconstruction resulting from the lack of suitable bioengineered tissue for efficient innervation and muscle function restoration. |
| Databáze: | OpenAIRE |
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