Abstract

The musculoskeletal system is a vital body system that protects internal organs, supports locomotion, and maintains homeostatic function. Unfortunately, musculoskeletal disorders are the leading cause of disability worldwide. Although implant surgeries using autografts, allografts, and xenografts have been conducted, several adverse effects, including donor site morbidity and immunoreaction, exist. To overcome these limitations, various biomedical engineering approaches have been proposed based on an understanding of the complexity of human musculoskeletal tissue. In this review, the leading edge of musculoskeletal tissue engineering using 3D bioprinting technology and musculoskeletal tissue-derived decellularized extracellular matrix bioink is described. In particular, studies on in vivo regeneration and in vitro modeling of musculoskeletal tissue have been focused on. Lastly, the current breakthroughs, limitations, and future perspectives are described.

Highlights

  • The musculoskeletal system is a major body system comprising bones, cartilages, muscles, tendons, ligaments, and other connective tissues

  • In the remaining sections of this review, we describe the general approaches of decellularization and decellularized extracellular matrix (dECM) bioink formulation, discuss the essential considerations of dECM bioink in the 3D bioprinting process, summarize their applications in constructing musculoskeletal tissue analogs for tissue regeneration and in vitro modeling, and conclude with some perspectives on the future and challenges of dECM-based bioinks

  • The matured muscle constructs were implanted into the injured tibialis anterior muscle, and the results demonstrated that muscle dECM (mdECM) facilitates rapid de novo muscle regeneration

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Summary

Introduction

The musculoskeletal system is a major body system comprising bones, cartilages, muscles, tendons, ligaments, and other connective tissues. Autografts, allografts, and xenografts have been implanted into defective sites; there are several drawbacks, including a shortage of donor organs and immune rejection [4] To overcome these limitations, innovative tissue engineering approaches have been proposed based on an understanding of the complexity of human musculoskeletal tissues. By depositing multiple biomaterials and living cells layer-by-layer, 3D bioprinting can precisely define 3D complex constructs that structurally emulate natural tissues/organs. Due to these advantages and demands, several 3D bioprinting companies, such as EnvisionTEC (Detroit, MI, USA), REGENHU (Villaz-St-Pierre, Switzerland), Poetis (Pessac, France), Organovo (San Diego, CA, USA), and nScrypt (Orlando, FL, USA), have commercialized various 3D bioprinters; further technological development is ongoing [33]. To select an appropriate module for fabricating a tissue/organ construct with specific characteristics, it is important to understand their working mechanisms

Inkjet-Based 3D Bioprinting
Laser-Assisted 3D Bioprinting
Microextrusion-Based 3D Bioprinting
Bioinks for 3D Bioprinting of Living Constructs
Decellularization
Compositional Quantification of dECM
Solubilization of dECM
Considerations of dECM Bioink for 3D Bioprinting
Printability
Cell Viability
Mechanical and Compositional Stability
Skeletal Muscle
Cartilage
Ligament
Three-Dimensional bioprinting of Vascularized Musculoskeletal Tissue
Three-Dimensional bioprinting of Innervated Musculoskeletal Tissue
Interfaces of Musculoskeletal Tissues
Findings
Conclusions and Perspectives
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