Abstract

As part of regenerative medicine, artificial, hierarchical tissue engineering is a favorable approach to satisfy the needs of patients for new tissues and organs to replace those with defects caused by age, disease, or trauma or to correct congenital disabilities. However, the application of tissue engineering faces critical issues, such as the biocompatibility of the fabricated tissues and organs, the scaffolding, the complex biomechanical processes within cells, and the regulation of cell biology. Although fabrication strategies, including the traditional bioprinting, photolithography, and organ‐on‐a‐chip methods, as well as combinations of fabrication processes, face many challenges, they are methods that can be used in hierarchical tissue engineering. The strategic approach to synthetic, hierarchical tissue engineering is to use a combination of several technologies incorporating material science, cell biology, additive manufacturing (AM), on‐a‐chip strategies, and biomechanics. Herein, in a review, the current materials and biofabrication strategies of various artificial hierarchical tissues are discussed based on the level of tissue complexity from nano to macrosize and the adaptive interactions between cells and the scaffolding surrounding the incorporated cells.

Highlights

  • In regenerative medicine technology, 3D printing is commonly used for scaffold construction to facilitate cell growth to replace and repair tissues or organs damaged by an accident or congenital disabilities

  • The gelatin methacryloyl (GelMA) and the PEGMA in 3D-bioprinted cartilage support the creation of hyaline-like cartilage, which allows the formation of fibrocartilage.[75]

  • This method was successfully used for tissue engineering in artificial skin fabrication,[83] and multilayer skin for patients with skin damage was fabricated by combining collagen, NIH3T3 fibroblasts, and HaCat keratinocytes

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Summary

Setiawati Faculty of Pharmacy Sanata Dharma University

With a proper scaffold material, an adequate microenvironment for cell proliferation, cell adhesion, and cell–cell interactions can be achieved.[10]. Www.advancedsciencenews.com www.advnanobiomedres.com biomimetic factors from the extracellular matrix (ECM) to scaffolds fabricated using synthetic polymers.[12] The cellular physiology, including survival, migration, growth, and differentiation, is determined by the microenvironment provided by the cells’ scaffold.[13] The biological interactions between the cells and the scaffold are combinations of receptor-mediated and mechanical-mediated signals, so-called mechanotransduction, that regulate the phenotype and the function of the cells. The 3D bioprinting process requires a biocompatible ink that contains biological materials for the cells’ scaffold and living cells for tissue fabrication.[18] If the complex, natural, hierarchical structures of tissues and organs are to be mimicked, the ultimate strategies, including material selection, the fabrication method, and the mimicking of their microenvironment, must be fully understood. A comprehensive discussion of this topic would include the materials to be used, the fabrication method, and the engineering of the fabricated scaffold to achieve the proper hierarchical structure so that the fabricated tissue or organ can be used for regenerative medicine

Hierarchical Tissues
Effects of AM on Tissue Engineering
Inkjet Bioprinting
Extrusion-Based Bioprinting
Laser-Assisted Bioprinting
Stereolithography-Based Bioprinting
Microfluidics for Tissue Engineering
Microfluidics in Hierarchical Tissue Fabrication
Microenvironment Stimulation in Microfluidics
Materials for Hierarchical Tissue Fabrication
Biomaterials
Synthetic Materials
Cells in Tissue-Engineering Applications
Biophysical Cell Responses in Tissue Engineering
Mechanotransduction and Mechanosignaling
Chemical Compositions and Manipulating Cell Responses
Micro and Macroenvironments for Cellular Responses
Implementation of Hierarchical Tissue Constructs
Present Challenges and Perspectives
Conflict of Interest
Full Text
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