Accelerated Innervation of 3D Bioprinted Muscle Construct with Pre-Fabricated Neuromuscular Junctions and Neurotrophic Factor Release System
Abstract
Extensive damage to skeletal muscle is a clinically challenging problem both soldiers and civilians, alike. Extensive skeletal muscle injuries due to trauma, congenital defects, or diseases result in functional impairment with severe physical deformity. In addition, in many cases, muscle defects involve nerve damage, which leads to another clinical problem; i.e. denervation, atrophy and permanent functional disability. The standard of care is an autologous muscle flap transfer. However, host muscle tissue availability and donor site morbidity often complicate implementation of this strategy. Tissue-engineered muscles represent an alternative means to repair volumetric muscle defects. Although these tissue-engineered muscles have provided potential solutions to regenerate contractile muscle tissue in vivo, the issues related to peripheral nerve regeneration and innervation have not been adequately addressed to date. In this project, we aim to develop an implantable bioprinted engineered muscle prototype with pre-formed neuromuscular junctions (NMJs) and an integrated neurotrophic factor controlled release system. These technologies are intended to accelerate integration with host peripheral nerve to achieve rapid functional muscle restoration. We will develop a 3-dimensnional (3D) bioprinted muscle construct prototype with NMJ pre-formation and neurotrophic factor controlled release to promote rapid nerve integration and innervation of muscle constructs for functional restoration. The muscle construct prototype will be validated both in vitro and in vivo, in terms of muscle regeneration, peripheral nerve regeneration, innervation, and clinical feasibility for restoring muscle function. We will optimize the prototype and develop manufacturing processes, standard operating procedures (SOPs) and batch records (BRs) to support an FDA Pre-IND application as a step towards clinical deployment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 25, 2021
- Accession Number
- AD1162790
Entities
People
- Ickhee Kim
- James J Yoo
- Ji Hyun Kim
- John Jackson
- Sang J. Lee
- Young Min Ju
Organizations
- Wake Forest University