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International Journal of Bioprinting Progress in bioprinting of bone
The multipotency of stem cells makes them a popular biologically active ions like strontium (Sr ) has been
2+
alternative to cell lines and primary bone cells. Numerous reported to enhance bone formation [77,78] . In addition, as
studies have been conducted on bone bioprinting using an alkaloid component extracted from Chinese traditional
MSCs, such as bone MSCs (BMSCs) and human nasal medicines such as astragalus and coptis, berberine also
turbinate-derived MSCs (hTMSCs) . An intriguing has an osteogenic effect and antibacterial properties .
[56]
[79]
finding is that MSCs can be obtained from induced Stiffer biomaterials also trigger higher MSC osteogenic
pluripotent stem cells (iPSCs), which can overcome the differentiation as the mechanical properties of the
problem of limited quantities of autologous MSCs . biomaterial affect cellular activity . Moreover, it has been
[57]
[72]
Furthermore, adipose-derived stem cells (ADSCs) are reported that exogenous electrical stimulation can increase
plenty in the human body and are surgically accessible, mineralization . In short, using appropriate physical and
[80]
which makes them another striking source for chemical cues, the stem cell activities, particularly the
bioprinting . To support therapeutic revascularization in osteogenesis, can be controlled and enhanced.
[13]
bioprinted tissue, ECs [26,52,53] , endothelial progenitor cells
(EPCs) , or endothelial colony-forming cells (ECFCs) 2.6. Mechanical enhancement
[58]
[59]
have been cocultured with the above-mentioned cells [59-61] . Constructs bioprinted using natural hydrogels have a
2.5. Osteogenesis low modulus of compression (<10 kPa) [74,81] and degrade
rapidly, losing most of their structural integrity within a
In principle, bioprinted bone should promote and facilitate short-time . Despite the design of delicate gradients
[82]
the proliferation and osteogenesis of stem cells and with different concentrations of GelMA hydrogel,
osteoprogenitor cells by the release of specific cytokines, mechanical stability could not be maintained for more
such as transforming growth factor (TGF-β), interferons, than 21 days in culture as a result of the degradation of
and interleukins (IL) [62,63] . In addition, bioprinted bone GelMA . Furthermore, the polyP·Ca coated alginate/
[52]
2+
should possess osteoinduction capabilities by depositing gelatin construct lost its mechanical stability after a 5-day
bone-related proteins (e.g., BMPs, insulin-like growth culture . Young’s modulus (GPa) and tensile/compressive
[75]
factors, and fibroblast growth factor [FGFs]) [64-66] . Last strength (MPa) of native bone are in some orders of
but not least, the structure should provide a porous magnitude higher than those of hydrogel-based bioinks. It
microenvironment for the differentiation of bone cells, is problematic to use hydrogel-only constructs in clinical
facilitating the synthesis of minerals, and collagenous applications, and thus, developing constructs with a high
tissue . and retainable mechanical strength is urgent.
[67]
Some of the above-mentioned studies have shown that Blending mechanically strong particles within a
stem cell differentiation is preserved in bioprinted bone, hydrogel may provide some reinforcement to bioprinted
and their osteogenic differentiation can be modulated by constructs [51,74] . The compression modulus of cell-laden
utilizing the right printing process, biomaterials, design, constructs containing alginate, polyvinyl alcohol (PVA),
and bioactive factors . The addition of BMP-2 and TGF-β and HAp was 10.3 kPa, but this value dropped to 2.4 kPa
[68]
usually results in greater osteogenic differentiation [69,70] . As after 14 days of culture . An elastic modulus of 0.55 MPa
[83]
to bioink materials, an alginate-based hydrogel supports has been measured for the bioprinted TCP-collagen
the viability of MSCs and retains their osteogenic capacity constructs , which was less than the elastic modulus of
[84]
in bioprinted bone . MeHA has also been demonstrated trabecular bone (20 – 52 MPa) . Using silk fibroin/ionic-
[71]
[85]
to trigger osteogenic differentiation of hBMSCs in doped β-TCP, a multilayer structure has been prepared,
bioprinted constructs without exogenous osteogenic which provided slightly enhanced mechanical properties
factors . The GelMA scaffold was also demonstrated to (static compression modulus of 0.66 MPa and dynamic
[72]
induce mineralization of MG63 osteoblasts and primary mechanical properties of 2.17 – 3.19 MPa) . Furthermore,
[86]
normal human osteoblasts (NHOst) without requiring nanozirconium dioxide powder was blended in PCL, and
any additional osteogenic factors . In addition, the HAp Young’s modulus and compressive strength increased by
[73]
plays an important role in the osteogenic differentiation ~0.4 and 0.5 times, respectively, as compared with the PCL-
of preosteoblast cells in vitro . A surge of mineralization [87]
[74]
in SaOS-2 cell-embedded hydrogel was observed on only scaffold . In another case, bredigite was mixed with
2+
overlaying polyP·Ca -complex to the bioprinted alginate/ nanosheets of graphene oxide which was reduced by bovine
gelatin hydrogel . Furthermore, bone scaffolds that were serum albumin, and the addition of reduced graphene
[75]
oxide enhanced the mechanical properties of scaffolds .
[88]
composed of decellularized porcine bone had significantly
enhanced osteogenic gene expression, without the use For significant reinforcement of the mechanical
of an osteogenic medium . Besides, the addition of properties of bioprinted constructs, thermoplastics or
[76]
Volume 9 Issue 1 (2023) 81 https://doi.org/10.18063/ijb.v9i1.628

