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ORIGINAL RESEARCH article

Front. Bioeng. Biotechnol.
Sec. Tissue Engineering and Regenerative Medicine
Volume 12 - 2024 | doi: 10.3389/fbioe.2024.1476370

Accelerated Innervation of Biofabricated Skeletal Muscle Implants Containing a Neurotrophic Factor Delivery System

Provisionally accepted
Vladimir S. Mashanov Vladimir S. Mashanov 1Erika Billman Erika Billman 1Aurelia Poerio Aurelia Poerio 1,2Mary Kaufmann Mary Kaufmann 1,3Dehui Lai Dehui Lai 1,4Bill Vaughan Bill Vaughan 1Ickhee Kim Ickhee Kim 1Young Min Ju Young Min Ju 1Anthony Atala Anthony Atala 1James Yoo James Yoo 1Ji Hyun Kim Ji Hyun Kim 1*
  • 1 Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University, Winston-Salem, United States
  • 2 Institut Jean Lamour, Faculté des sciences et technologies, Université de Lorraine, Nancy, Lorraine, France
  • 3 School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • 4 Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China

The final, formatted version of the article will be published soon.

    Volumetric muscle loss (VML) is one of the most severe and debilitating conditions in orthopedic and regenerative medicine. Current treatment modalities often fail to restore the normal structure and function of the damaged skeletal muscle. Bioengineered tissue constructs using the patient's own cells have emerged as a promising alternative treatment option, showing positive outcomes in fostering new muscle tissue formation. However, achieving timely and proper innervation of the implanted muscle constructs remains a significant challenge. In this study, we present a clinically relevant strategy aimed at enhancing and sustaining the natural regenerative response of peripheral nerves to accelerate the innervation of biofabricated skeletal muscle implants.We previously developed a controlled-release neurotrophic factor delivery system using poly (lactic-co-glycolic acid) (PLGA) microspheres encapsulating ciliary neurotrophic factor (CNTF) and glial cell line-derived neurotrophic factor (GDNF). Here, we incorporate this neurotrophic factor delivery system into bioprinted muscle constructs to facilitate innervation in vivo. Our results demonstrate that the neurotrophic factors released from the microspheres provide a chemical cue, significantly enhancing the neurite sprouting and functional innervation of the muscle cells in the biofabricated muscle construct within 12 weeks post-implantation. Our approach provides a clinically applicable treatment option for VML through accelerated innervation of biomanufactured muscle implants and subsequent improvements in functionality.

    Keywords: bioengineered skeletal muscle, innervation, neurotrophic factors, CNTF, gdnf, Controlled-release delivery system

    Received: 05 Aug 2024; Accepted: 14 Oct 2024.

    Copyright: © 2024 Mashanov, Billman, Poerio, Kaufmann, Lai, Vaughan, Kim, Ju, Atala, Yoo and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ji Hyun Kim, Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University, Winston-Salem, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.