Publications by authors named "Ickhee Kim"

3 Publications

  • Page 1 of 1

Pelvic floor muscle function recovery using biofabricated tissue constructs with neuromuscular junctions.

Acta Biomater 2021 02 13;121:237-249. Epub 2020 Dec 13.

Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1094, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.actbio.2020.12.012DOI Listing
February 2021

Neural cell integration into 3D bioprinted skeletal muscle constructs accelerates restoration of muscle function.

Nat Commun 2020 02 24;11(1):1025. Epub 2020 Feb 24.

Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.

A bioengineered skeletal muscle construct that mimics structural and functional characteristics of native skeletal muscle is a promising therapeutic option to treat extensive muscle defect injuries. We previously showed that bioprinted human skeletal muscle constructs were able to form multi-layered bundles with aligned myofibers. In this study, we investigate the effects of neural cell integration into the bioprinted skeletal muscle construct to accelerate functional muscle regeneration in vivo. Neural input into this bioprinted skeletal muscle construct shows the improvement of myofiber formation, long-term survival, and neuromuscular junction formation in vitro. More importantly, the bioprinted constructs with neural cell integration facilitate rapid innervation and mature into organized muscle tissue that restores normal muscle weight and function in a rodent model of muscle defect injury. These results suggest that the 3D bioprinted human neural-skeletal muscle constructs can be rapidly integrated with the host neural network, resulting in accelerated muscle function restoration.
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http://dx.doi.org/10.1038/s41467-020-14930-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039897PMC
February 2020

A novel decellularized skeletal muscle-derived ECM scaffolding system for in situ muscle regeneration.

Methods 2020 01 3;171:77-85. Epub 2019 Jul 3.

Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. Electronic address:

The cell-based tissue engineering strategies have gained attention in restoring normal tissue function after skeletal muscle injuries; however, these approaches require a donor tissue biopsy and extensive cell expansion process prior to implantation. In order to avoid this limitation, we developed a novel cell-free muscle-specific scaffolding system that consisted of a skeletal muscle-derived decellularized extracellular matrix (dECM) and a myogenic factor, insulin growth factor-1 (IGF-1). Rheological, morphological, and biological properties of this muscle-specific scaffold (IGF-1/dECM) as well as collagen and dECM scaffolds were examined. The cell viability in all scaffolds had over 90% at 1, 3, and 7 days in culture. The cell proliferation in the IGF-1/dECM was significantly increased when compared with other groups. More importantly, the IGF-1/dECM strongly supported the myogenic differentiation in the scaffold as confirmed by myosin heavy chain (MHC) immunofluorescence. We also investigated the feasibility in a rabbit tibialis anterior (TA) muscle defect model. The IGF-1/dECM had a significantly greater number of myofibers when compared to both collagen and dECM groups at 1 and 2 months after implantation. We demonstrated that this novel muscle-specific scaffolding system could effectively promote the muscle tissue regeneration in situ.
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http://dx.doi.org/10.1016/j.ymeth.2019.06.027DOI Listing
January 2020