Bioprinting a cell‐laden matrix for bone regeneration: A focused review

Abstract

Although many efforts have been made to regenerate the bone lesions, existing challenges can be mitigated through the development of tissue engineering scaffolds. However, the weak control on the microstructure of constructs, limitation in preparation of patient-specific and multilayered scaffolds, restriction in the fabrication of cell-laden matrixes, and challenges in preserving the drug/growth factors' efficacy in conventional methods have led to the development of bioprinting technology for regeneration of bone defects. So in this review, conventional 3D printers are classified, then the priority of the different types of bioprinting technologies for the preparation of the cell/growth factor-laden matrixes are focused. Besides, the bio-ink compositions, including polymeric/hybrid hydrogels and cell-based bio-inks are classified according to fundamental and recent studies. Herein, different effective parameters, such as viscosity, rheological properties, cross-linking methods, biodegradation biocompatibility, are considered. Finally, different types of cells and growth factors that can encapsulate in the bio-inks to promote bone repair are discussed, and both in vitro and in vivo achievement are considered. This review provides current and future perspectives of cell-laden bioprinting technologies. The restrictions and challenges are identified, and proper strategies for the development of cell-laden matrixes and high-performance printable bio-inks are proposed.

An Overview of Extracellular Matrix-Based Bioinks for 3D Bioprinting

“…Traditional 3D printing technologies first prepare the scaffold; then, the cells are infused and inoculated prior to implantation. However, this method cannot ensure uniform distribution of cells on the scaffold, making it difficult to obtain ideal new tissue ( Ghorbani et al, 2021 ). 3D bioprinting technology can print cells and scaffolds at the same time; different cells can be stacked in specific locations; and the biological behavior and performance of cells can be modulated by active agents ( Bendtsen et al, 2017 ).…”

Strategies for Enhancing Vascularization of Biomaterial‐Based Scaffold in Bone Regeneration

“…However, the recent introduction of 3-D bioprinting (Inkjet-based, extrusion, and laser-based bioprinting) produces functional bioscaffolds using assimilation of cells, biomaterials, and biomolecules (Bioinks) through bioprinting computer software, making them patientspecific. [35,36,37]…”

“…Predominantly, in clinical trials, the traditional scaffolds are constructed with the incorporation of cellular cultures, are transplanted at the site of the defect. However, the recent introduction of 3‐D bioprinting (Inkjet‐based, extrusion, and laser‐based bioprinting) produces functional bioscaffolds using assimilation of cells, biomaterials, and biomolecules (Bioinks) through bioprinting computer software, making them patient‐specific [35,36,37] …”

Bioprinted hASC‐laden collagen/HA constructs with meringue‐like macro/micropores

“…Bioprinting for fabricating cell‐laden porous scaffolds has become one of the most important processes in tissue engineering. 1 , 2 , 3 , 4 , 5 As reported by several researchers, cell‐laden scaffolds offer numerous advantages, such as versatility in efficiently loading different cell types in a desired position and ease in cell density control compared with conventional scaffolds seeded with cells. 1 , 2 , 3 , 4 , 5 Although bioprinted cell‐laden scaffolds demonstrate outstanding biological activities, they present shortcomings that must be solved.…”

“… 1 , 2 , 3 , 4 , 5 As reported by several researchers, cell‐laden scaffolds offer numerous advantages, such as versatility in efficiently loading different cell types in a desired position and ease in cell density control compared with conventional scaffolds seeded with cells. 1 , 2 , 3 , 4 , 5 Although bioprinted cell‐laden scaffolds demonstrate outstanding biological activities, they present shortcomings that must be solved. For example, cells encapsulated in a bioink exhibit limited cellular responses because of the low porosity within printed cell‐laden struts, thereby inducing low cell‐to‐cell or cell‐to‐biomaterial interactions; additionally, the cell‐laden structure cannot sustain its complex three‐dimensional (3D) geometry owing to the inferior mechanical properties of the matrix material, i.e., hydrogel.…”