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International Journal of Bioprinting 3D bioprinting techniques & hydrogels materials

whereas scaffolds with larger apertures (>300 µm) promote 3.3.4. Growth factors
osteogenic differentiation and vascularization. 190,191 The cytokine TGF-β, belonging to the TGF-β superfamily,
Scaffolds with vertical porosity and pore size gradients can plays a crucial role in embryonic bone development
promote the bidirectional differentiation of MSCs. 192,193 and the homeostasis of bone and cartilage after birth;
Moreover, future studies should consider both the anti- it is also capable of facilitating the early development of
inflammatory and vascularization capabilities of stents. chondrocytes. In osteochondral tissue engineering, Gao
200
Given the complexity of 3D printing cellular spheres, et al. 3D-printed a double-layer hydrogel scaffold; the
it is necessary to develop an integrated platform to upper layer was loaded with TGF-β to facilitate cartilage
achieve efficient manufacturing of spheres through 3D differentiation, and the lower layer employed TCP to
printing technology. 194 enhance the mechanical properties of the hydrogel. 201

3.3.2. Chondrocytes and osteocytes Bone morphometric proteins (BMPs) are cytokines also
Although scaffold-coated MSCs exhibit high cell viability from the TGF-β family that exhibit structural similarities.
in bone repair, they may still lack the ability to promote In contrast to TGF-β, BMPs facilitate differentiation
cell differentiation and new bone formation in the absence at all stages of chondrocyte cell differentiation. The
of growth factors. Therefore, chondrocytes or osteoblasts spatiotemporal integration of these growth factors can
are sometimes loaded directly onto the scaffold to enhance also restore osteochondral tissue by inducing cartilage
bone repair. Diloksumpan et al. utilized chondrocytes formation and osteogenesis within a single scaffold. Qiao
202
containing hydrogels, bioceramics, and polymers to et al. fabricated a three-layer scaffold through 3D printing,
design a hybrid 3D-printed scaffold with a mechanically in which BMP-7 and TGF-β1 were contained in the cartilage
strengthened osteochondral interface, offering valuable surface layer; TGF-β1 was present in the calcified cartilage
insights for designing interfaces and materials in layer; BMP-2 was located in the subchondral bone layer.
regenerative medicine. Zhai et al. created a PEG- This successfully enabled the precise delivery of various
195
clay nanocomposite crosslinked hydrogel scaffold with cytokines to the three-layer structure of osteochondral
osteoblasts via a two-channel 3D printing technique. The tissue and enhanced bone regeneration (Figure 3i).
203
scaffold allows osteoblasts to obtain oxygen and nutrients,
providing superior bone protection. 196 However, questions remain regarding the application
Studies have demonstrated that chondrocytes exhibit of TGF-β. Excessive TGF-β can lead to side effects on
superior proliferation and cell functionality on HA bone tissue, possibly worsening OA; thus, further research
hydrogels, whereas osteoblasts exhibit better proliferation is warranted to determine the appropriate dosage.
and cell function on type I collagen (COL I) hydrogels. Additionally, more investigation is required to effectively
197
Therefore, to achieve better repair results, it is necessary promote bone regeneration.
to choose the appropriate hydrogel material for the loaded Stromal cell-derived factor-1α (SDF-1α) is a potent
cells. Further studies are warranted to verify the efficacy of chemokine that can recruit BMSCs and plays a pivotal role
the direct loading of chondrocytes or osteoblasts. in endogenous tissue repair, as demonstrated in a rotator
cuff injury model. 204,205 The conventional approach for
3.3.3. Mixed cells
Given that bone cartilage inherently possesses a layered incorporating SDF-1α into scaffolds involves direct protein
structure, researchers have endeavored to load distinct integration, but rapid double osmosis and degradation
cells at various levels to fabricate 3D-printed scaffolds limit its sustained impact on stem cell recruitment. To
loaded with multiple types of cells to augment the effect of address this issue, researchers have explored various
bone cartilage repair. Critchley et al. designed a 3D-printed methods, such as chemical fixation and co-encapsulation
biphasic fiber-reinforced hydrogel scaffold loaded with other growth factors, to enhance cartilage repair. 206,207
with MSCs while highlighting its cartilage layer with However, these methods may inadvertently recruit other
infrapatellar fat pad-derived stem/stromal cells (FPSCs) cells, such as endothelial progenitor cells, lymphocytes, and
and chondrocytes, achieving favorable therapeutic effects macrophages, which can impede the efficacy of cartilage
208
198
in a goat model. Zhang et al. employed dual-channel regeneration. In order to overcome this challenge,
extrusion bioprinting technology to generate innovative Zeng et al. chemically crosslinked HAP and hydrogel
anisotropic bicellular living hydrogels (ABLHs). The upper to create a mechanically robust scaffold. Subsequently,
layer is embedded with articular cartilage progenitor cells they chemically crosslinked ligands and loaded SDF-1α-
(ACPCs) derived from cartilage to promote cartilage coated poly(lactide-co-acetic acid) (PLGA) nanospheres
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formation, and the lower layer is populated with BMSCs to to specifically capture BMSCs in vivo (Figure 3ii).
promote bone formation. 199 Additionally, they utilized pre-designed bioinks for in situ

Volume 10 Issue 6 (2024) 79 doi: 10.36922/ijb.4472