Page 475 - IJB-9-6
P. 475
International Journal of Bioprinting Bioprinting cell-laden protein-based hydrogel
biodegradation, and crosslinking, as well as biochemical permit the fabrication of complex 3D structures with high
factors, including chemical structure, growth factors, reproducibility and shape fidelity [11-13].
and signaling molecules, on protein structure and cell Hydrogels are popularly employed as bioinks in the
behavior. Additionally, key considerations for bioprinting bioprinting process because of their chemical structure
PBHs and their impact on the successful regeneration of and the favorable 3D environments they provide for
tissues are discussed. Furthermore, the review highlights cellular growth [14-17] . Incorporating cells into inks (i.e.,
current advancements, existing challenges, and promising biomaterials or biological materials) to create a “bioink”
prospects in the development of cell-laden PBHs for is the cornerstone of producing intricate, biologically
bioprinting applications and the regeneration of bone applicable 3D tissue structures [18,19] . The use of PBHs as
and cartilage.
bioinks for bioprinting has several advantages over other
hydrogel systems. PBHs are biocompatible, biodegradable,
Keywords: Bioprinting; Protein; Bioink; Cartilage; Bone; and can be functionalized with cell adhesion peptides and
Tissue engineering growth factors (GFs) to enhance cell behavior and tissue
regeneration [20,21] . Moreover, they can be crosslinked in
situ by various mechanisms, such as physical, chemical, or
enzymatic crosslinking, to achieve the desired mechanical
1. Introduction properties and stability. In recent years, several PBHs have
The field of tissue engineering (TE) and regenerative been developed for the bioprinting of cartilage and bone
medicine may undergo a revolution due to the development tissue constructs. These hydrogels offer several advantages
of bioprinting, a rapidly developing technology. An over other materials, such as synthetic polymers or
important application of bioprinting is in cartilage and decellularized extracellular matrix (ECM) scaffolds. PBHs,
bone TE, where it can be used to fabricate complex three- such as collagen, gelatin, and fibrin, are biocompatible and
dimensional (3D) structures that mimic the structure and biodegradable and can support cell adhesion, proliferation,
mechanical properties of natural tissues . As a potential and differentiation [22-24] . By providing spatial factors, such as
[1]
method for fabricating cartilage and bone tissue constructs, porosity, protein alignment, and network density, the tissue
bioprinting of cell-laden protein-based hydrogels (PBHs) structure can influence cellular behavior, shape, migration,
has emerged in recent years [2-4] . and fate. Therefore, PBHs aim to replicate the ECM’s
complex and unique structure to develop functional tissue
Traditional scaffolds cannot efficiently transport constructs that can mimic the native tissue’s mechanical and
nutrients or exchange oxygen without porous structures biological properties [25-28] . The ability to imitate the native
interconnected in a complex geometry, and cells are tissues’ ECM and the tendency to experience shear-thinning
typically deposited randomly using TE fabrication before regaining their original shape are other desirable
techniques [5,6] . In order to overcome these barriers, 3D features of protein-based materials. Furthermore, protein-
bioprinting techniques can be used to construct cell- based polymers can be utilized to adjust the rheological and
laden 3D structures [7,8] . By using cell-laden hydrogels, biochemical properties of bioinks, thereby enhancing the
bioprinting makes tissue constructs with a high cell shape fidelity [29-32] . Further, these materials are renewable
density, which plays a vital role in tissue regeneration. and green compared to fossil-derived synthetic polymers,
Bioprinting technology is divided into two distinct groups and their availability and ease of large-scale production
that are not mutually exclusive. Two basic categories can be via bioengineering methodologies and biotechnological
distinguished: distributed versus aggregated cells and single techniques make them attractive to researchers [33,34] . Thus
versus multi-cellular. Cell aggregate bioprinting involves far, more natural proteins of animal origin have been used
embedding preformed cell aggregates in bioinks and in the fabrication of hydrogels, the reasons for which are
then printing them. Unlike single-cell bioprinting, which easier access, lower cost, and simplicity of extraction,
involves printing one cell at a time, multi-cell bioprinting which will be followed by their introduction and review
involves suspending several cells in bioink and depositing in the synthesis of biological inks for osteochondral and
[9]
them in a filament or droplet . The incorporation of cartilage TE.
multiple cell types, such as chondrocytes and osteoblasts,
into bioprinted osteochondral tissue constructs enhances The protein sequence of hydrogels can significantly
the formation of a functional interface between cartilage influence bioprinting processes and tissue constructs [35,36] .
[10]
and bone . The fabrication of cartilage and bone tissue PBHs differ in terms of their mechanical properties,
constructs has been achieved using multi-cell bioprinting degradation rates, and cell adhesion properties, which can
technologies, including inkjet printing, extrusion-based have a major impact on the printability of hydrogels and
printing, and laser-assisted printing. These technologies the behavior of cells. As an example, collagen hydrogels
Volume 9 Issue 6 (2023) 467 https://doi.org/10.36922/ijb.1089

