Page 171 - IJB-10-3

International Journal of Bioprinting 3D bone: Current & future

3D scaffolds made of HA-containing composites Bioactive glass can also be added to thermoplastic
with good biological and mechanical properties. HA materials of a hard scaffold or even mixed into
is often mixed with microparticles or nanoparticles hydrogels as nanoparticles, both of which can be
when producing hard scaffold materials or hydrogels used in DIW and DLP bioprinters. 78,79
and is used in FDM, DIW, SLA, SLS, inkjet, DLP, and
LAB techniques. 72-74 5. Recent advances in 3D bone
(ii) TCP: TCP is a preferred material for developing tissue bioprinting
bioceramic-containing scaffolds. Its chemical Although 3D bioprinting appears to be the future of tissue
formula is Ca (PO ) and has three polymorphic engineering, we are still far from producing functional
3
4 2
forms, β-TCP, α-TCP, and α’-TCP. Among these, tissues of relevant size that are suitable for human
β-TCP is stable with a melting temperature of transplantation. For example, 3D printing of blood vessels is
approximately 1150°C. At higher temperatures, a great challenge as we are currently unable to create tissues
β-TCP transforms into α-TCP and subsequently of a size that exceeds the diffusion distance of nutrients
to the unstable α’-TCP above 1400°C. Hence, only and oxygen supply. Likewise, the clinical translation of
α-TCP and β-TCP are used in bone replacement and cell-based strategies faces legal and regulatory limitations,
tissue engineering. Both forms of TCP have excellent as well as the risk of immune reactions and uncontrolled
bioactivity and biocompatibility and degrade faster cell differentiation in the recipient’s body. In addition,
than HA. β-TCP is chemically more stable, but the optimization of hydrogels used for bioprinting can be
α-TCP displayed faster bone formation in vivo due complicated. Due to the challenges of 3D bioprinting, there
to its better solubility in an aqueous solution. Like have been no successful studies on 3D-bioprinted active,
HA, TCP can be used to produce hard scaffold cell-containing human bone transplantation. 2,80-85 Despite
materials and hydrogels, and TCP composites can be the in vitro and in vivo experiments conducted (Table 6),
employed with the same printing techniques. 75,76 more studies are warranted before 3D-printed tissues can
(iii) Biphasic calcium phosphate: Both HA and TCP have be implemented for human transplantation.
their advantages and disadvantages in terms of bone Nonetheless, the transplantation of cell-free 3D-printed
formation and 3D bioprinting. Biphasic calcium rigid scaffolds and injectable bone replacement materials
phosphate is a mixture of HA and β-TCP in different has long been used in regenerative medicine, particularly
proportions, thereby enabling precise regulation of in dental repairs and bone replacement. These scaffolds are
their individual properties. Solubility is the most primarily printed with SLS 3D printers from bioceramics,
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important parameter that affects bone formation. bioglass, or metals. According to the ClinicalTrials.gov
Free calcium and phosphate ions can initiate bone database, there are less than 30 cases related to 3D-printed
formation, such that calcium ions have a direct effect bone implants in humans (Tables 7 and 8). Recently, Hao et
on osteoblasts. The calcium and phosphate ions also al. developed a bioink from a patient’s autologous platelet-
regulate the bone-oriented differentiation of MSCs. rich plasma (PRP) and PCL/β-TCP composites. The active
Furthermore, inorganic phosphate ions regulate scaffold was bioprinted and transplanted into the patient
the expression of mineralization-related genes, and with a good outcome. 86
the long-term release of inorganic phosphate ions
enhances the collagen mineralization process. Higher 6. Conclusion
solubility speeds up the bone formation process, but
excessive calcium levels might be deleterious to the The dynamic advancement of 3D bioprinting is
bone cells. In this regard, the solubility of ceramics encouraging for the future of tissue engineering. Due
could be optimized based on the HA/β-TCP ratio. to the interdisciplinary aspect of 3D bioprinting, the
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current limitations (i.e., in human transplantation) can
(iv) Bioactive glass: Bioactive glass is a surface-reactive be addressed by technological advancements and a better
glass-ceramic biomaterial. When implanted into the understanding of the underlying biological processes.
body, the material forms a layer similar to that of HA
on the surface. The basis of bioactive glass is silicon A major obstacle in clinically implementing 3D
dioxide (SiO ), calcium oxide (CaO), sodium oxide bioprinting lies in the intricate structure of bone tissues,
2
(Na O), and phosphorus tetraoxide (P O ), but may which makes it challenging to replicate the complex
2
2
5
also contain calcium, magnesium, copper, zinc, and microarchitecture, including hierarchical organization
silver ions. Bioactive glass can be used for implants, and vascular networks. Future studies should emphasize
fabricated with SLS or SLA 3D printing technology. refining bioink formulations for more sophisticated
Volume 10 Issue 3 (2024) 163 doi: 10.36922/ijb.2056