Abstract

The native tissues are complex structures consisting of different cell types, extracellular matrix materials, and biomolecules. Traditional tissue engineering strategies have not been able to fully reproduce biomimetic and heterogeneous tissue constructs because of the lack of appropriate biomaterials and technologies. However, recently developed three-dimensional bioprinting techniques can be leveraged to produce biomimetic and complex tissue structures. To achieve this, multicomponent bioinks composed of multiple biomaterials (natural, synthetic, or hybrid natural-synthetic biomaterials), different types of cells, and soluble factors have been developed. In addition, advanced bioprinting technologies have enabled us to print multimaterial bioinks with spatial and microscale resolution in a rapid and continuous manner, aiming to reproduce the complex architecture of the native tissues. This review highlights important advances in heterogeneous bioinks and bioprinting technologies to fabricate biomimetic tissue constructs. Opportunities and challenges to further accelerate this research area are also described.

Highlights

  • To engineer tissues for reconstructive surgical purposes, artificial matrices are conventionally fabricated and subsequently seeded with cells

  • The technology of 3D printing provides an attractive solution by employing multicomponent bioinks, which are by definition the materials that can be used for biofabrication [6], high resolution, and complex fabrication approaches can be employed to bioprint tissue constructs. 3D bioprinting has opened new avenues in mimicking the heterogeneous and complex native tissues

  • gelatin methacryloyl (GelMA) is characterized by combining cell biocompatibility properties of gelatin with crosslinkability and mechanical strength conferred by methacryloyl component [3,33,77], which becomes an increasingly important biomaterial for 3D bioprinting [33,77]

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Summary

Introduction

To engineer tissues for reconstructive surgical purposes, artificial matrices are conventionally fabricated and subsequently seeded with cells. The lack of appropriate control over spatial organization and components of commonly developed tissues is largely responsible for limited capability to produce biomimetic complex structures To solve this problem, the technology of 3D printing provides an attractive solution by employing multicomponent bioinks, which are by definition the materials that can be used for biofabrication [6], high resolution, and complex fabrication approaches can be employed to bioprint tissue constructs. Multiple techniques have been recently developed to solve this obstacle and achieve bioprinting multimaterials spontaneously in a continuous manner [18], aiming to reproduce the complex microarchitecture of the native tissues with varying types of biomaterials and cells These methods are primarily classified as extrusion, inkjet, laser-assisted, and UV-assisted bioprinting [19]. Challenges and future perspectives for better mimicking the complexity and function of the native tissues using 3D bioprinting approaches are described (see Fig. 1)

Multicomponent bioinks
Multicellular and stem cell–based bioinks
Biomolecule-contained bioinks
Methods to fabricate heterogeneous constructs
Multihead systems
Stereolithography
Digital light projector
Tissue fabrication using multicomponent bioinks and technologies
Multimaterial microfluidic bioprinting
Sacrificial template assisted printing
Cartilage and osteochondral tissue
Bone tissue
Adipose tissue
Cancer
Challenges and future outlook
28–54 Pa s at different PEG concentrations 12–14 mPa s
Findings
Conclusions
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