3D Bioprinted Human Skeletal Muscle Constructs for Muscle Function Restoration

Abstract

A bioengineered skeletal muscle tissue as an alternative for autologous tissue flaps, which mimics the structural and functional characteristics of the native tissue, is needed for reconstructive surgery. Rapid progress in the cell-based tissue engineering principle has enabled in vitro creation of cellularized muscle-like constructs; however, the current fabrication methods are still limited to build a three-dimensional (3D) muscle construct with a highly viable, organized cellular structure with the potential for a future human trial. Here, we applied 3D bioprinting strategy to fabricate an implantable, bioengineered skeletal muscle tissue composed of human primary muscle progenitor cells (hMPCs). The bioprinted skeletal muscle tissue showed a highly organized multi-layered muscle bundle made by viable, densely packed, and aligned myofiber-like structures. Our in vivo study presented that the bioprinted muscle constructs reached 82% of functional recovery in a rodent model of tibialis anterior (TA) muscle defect at 8 weeks of post-implantation. In addition, histological and immunohistological examinations indicated that the bioprinted muscle constructs were well integrated with host vascular and neural networks. We demonstrated the potential of the use of the 3D bioprinted skeletal muscle with a spatially organized structure that can reconstruct the extensive muscle defects.

3D Bioprinting: from Benches to Translational Applications

“…At 2 weeks after implantation, the muscle constructs were analyzed and shown to exhibit proper cell alignment and clusters of acetylcholine receptor (AChR) in the muscles fibers, as well as contact with neurofilaments showing nerve integration into the model (Figure G–I). Recently, Kim et al used the same ITOP bioprinting platform to fabricate a 3D implantable muscle constructs incorporating primary human muscle progenitor cells . Their bioprinted muscle constructs displayed a highly packed and organized structure of viable and aligned myofiber‐like structures.…”

Functional characterization of 3D contractile smooth muscle tissues generated using a unique microfluidic 3D bioprinting technology

“…Printed dECM-containing skeletal muscle constructs develop larger myotubes with a greater number of acetylcholine receptors compared to collagen printed muscle constructs. 36 Scientists have similarly shown enhanced differentiation and fiber alignment in 3D bioprinted iPSC derived cardiac muscle cell constructs when compared to cast 3D gels, which remained true after engraftment into mice. 35 Implanted skeletal muscle tissue has shown an ability to increase force generation of damaged muscles.…”

“…35 Implanted skeletal muscle tissue has shown an ability to increase force generation of damaged muscles. 36 Scientists have similarly shown enhanced differentiation and fiber alignment in 3D bioprinted iPSC derived cardiac muscle cell constructs when compared to cast 3D gels, which remained true after engraftment into mice. 37 Adipose-derived stem cells cultured in 3D were more able than those cultured in 2D to differentiate into smooth muscle cells, as determined by expression of smooth muscle actin and smoothelin.…”

Emerging Interventions for Elderly Patients—The Promise of Regenerative Medicine

“…3D printed organ constructs have been used in drug toxicology studies, with some suggesting their potential for the eventual replacement of experimental animals in some studies, and 3D printed anatomical models of organs are being used for the training of surgeons . Although the goal of 3D printing of replacement organs for transplantation has yet to be realized, significant progress has been made in animal models with the bioprinting of skin constructs for burns, as well as that of skeletal muscle constructs for the restoration of muscle function after volumetric muscle loss …”

“…87 Although the goal of 3D printing of replacement organs for transplantation has yet to be realized, significant progress has been made in animal models with the bioprinting of skin constructs for burns, as well as that of skeletal muscle constructs for the restoration of muscle function after volumetric muscle loss. 88,89…”