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International Journal of Bioprinting 3D bioprinting for musculoskeletal system

and integrity. Relative to the printing method used, the Another strategy is to combine gelatin with other
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printability of bioinks mainly depends on their rheological polymers, such as alginate or fibrinogen, to form a hybrid
characteristics and gelation kinetics. The printability of bioink. 30,31 Alginate, a polysaccharide derived from natural
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bioinks and the regulation of their physicochemical properties algae, is considered nontoxic and biologically inert to
on cell behaviors are the key to the regeneration of tissues mammalian cells. A major advantage of alginate is that
and organs. In general, bioinks need to possess some essential it can be rapidly crosslinked into a gel in the presence
characteristics that meet the basic requirements of 3D of divalent cations. Due to the lack of biological cues,
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bioprinting. Bioinks must have good biocompatibility, which alginate is often combined with other components such
requires that the chosen materials and their degradation as gelatin or collagen to form a bioink with biological
products must be nontoxic. Moreover, bioinks must provide activity. Fibrinogen, a glycoprotein found in the blood,
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cell adhesion sites that allow cells to survive, adhere, and can be converted to insoluble fibrin under the catalysis
proliferate. When used for printing different musculoskeletal of thrombin, forming a stable network structure to
tissues, bioinks must meet the tissue-specific requirements. promote tissue repair. Fibrin has good biocompatibility
For bone tissue, bioinks need to have angiogenic and and biodegradability, and there are some amino acid
osteogenic bioactivity as well as strong mechanical properties. sequences, such as RGD (Arg-Gly-Asp), in its structure
For skeletal muscle tissue, bioinks must be able to promote which can promote cell binding. Despite these
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cell alignment and myogenic differentiation and maturation advantages, mechanically stable constructs cannot be
to simulate muscle-oriented fibrous structures. For cartilage, bioprinted with pristine fibrinogen solutions because of
meniscus and IVD tissue, region-specific extracellular their low viscosity. Other components, such as alginate
matrix (ECM) deposition is a concern when designing and GelMA, are often incorporated to fibrinogen solutions
bioinks. Bioink materials commonly used for 3D bioprinting to improve their printing feasibility. 35,36 Hyaluronic acid
of musculoskeletal tissues include natural materials and (HA) is one of the main constituents of ECM and has been
synthetic materials. They provide suitable environment for extensively employed in tissue engineering because of its
cell growth and are used together with cells for bioprinting of anti-inflammatory and angiogenic properties. Due to its
target tissues or organs. versatility in structure modification, it has proved to be
an excellent bioink successfully applied to 3D bioprinting
2.2.1. Natural materials in recent years. The addition of HA can improve the
Natural materials such as collagen, gelatin, alginate, dispersion uniformity of the bioinks. Like gelatin, HA
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fibrinogen, hyaluronic acid, and decellularized extracellular has been mainly used in bioinks in combination with other
matrix (dECM) are common components in the bioink polymers. Recently, dECM-based bioinks have gained
formulation. As a key structural component of ECM, popularity in 3D bioprinting applications. As a novel
collagen has the advantages of low immunogenicity, good bioink derived from native tissue, a dECM-based bioink
biocompatibility, and biodegradation. The concentration retains native ECM components and necessary biological
of collagen affects the printing accuracy and the structural cues, which can enhance cell viability and tissue-specific
fidelity of the target constructs. The constructs printed functionality. 38,39 Lee et al. employed bone-derived dECM
using bioinks composed of low-concentration collagen to incorporate human adipose-derived stem cells and
are fragile, which is not conducive to the long-term printed 3D bone construct. It was found that bioinks
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maintenance of structural stability. To that end, Beketov composed of bone dECM and alginate promoted cell
et al. developed a bioink based on high-concentration viability and osteogenic differentiation compared with
collagen for the bioprinting of chondrocytes. pristine alginate-based bioinks.
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Cartilaginous tissue formation was observed 5–6 weeks
after subcutaneous implantation. Gelatin is the product of 2.2.2. Synthetic materials
partial hydrolysis of collagen, and its structure is similar to Synthetic polymers provide greater design flexibility and
that of ECM. Compared with collagen, gelatin has a higher structural complexity than natural polymers, which is
water solubility. Gelatin remains a gel at low temperature advantageous for bioprinting. With the incorporation
(<20°C) and dissolves into a liquid at high temperature of ECM elements and extra crosslinking, synthetic
(37°C). This temperature-sensitive property makes polymers can exhibit improved mechanical and biological
gelatin one of the most common bioink components. performance. Pluronic is a nontoxic FDA-approved block
However, gelatin-based bioinks alone cannot form a copolymer that is often used in 3D printing. Depending on
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stable network structure for subsequent cell culture. To their molecular weight and the ratio of poly (ethylene oxide)
address this, a common strategy is used to modify gelatin (PEO) to poly (propylene oxide) (PPO) in the Pluronic
with methacrylate groups to obtain a photocrosslinkable chain, several grades of Pluronics are available in different
hydrogel, namely gelatin methacrylate (GelMA). 29 states, such as liquid, paste, and solid. Among them,

Volume 10 Issue 1 (2024) 78 https://doi.org/10.36922/ijb.1037