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3D Bioprinting Photo-crosslinkable Hydrogels for Bone and Cartilage Repair
the formation of vascular networks and enhance bone term. Incorporation of MBGNs-rhBMP-2 in GelMA
regeneration . hydrogel could better control the release rate as well as
[59]
local concentration of rhBMP-2, while the MBGNs could
(3) Drugs and cytokines be fixed at the lesion site without clearance by body fluids.
Some drugs or cytokines play a key role in promoting This hydrogel showed strong ability in osteogenesis and
bone cell growth, modulating cell proliferation, and bone tissue regeneration in vivo.
differentiation as well as regulating the formation of In summary, photo-crosslinkable hydrogels have
ECM. Statins , osteoprotegerin , αvβ3 integrin incorporated nanomaterial components, cells, drugs,
[55]
[60]
antagonists , cathepsin K inhibitors , parathyroid and/or cytokines to produce viable bone tissue scaffolds.
[62]
[61]
hormone , transforming growth factor-β, and bone With the improved physical and biological properties,
[63]
morphogenetic protein (BMP) have all been considered it is of great significance to apply them in 3D printing
[64]
for stimulation of bone growth. Apart from drugs technology to broaden its application.
and cytokines for bone formation, angiogenic growth
factors, vascular endothelial growth factors (VEGF), 4. Applications of 3D bioprinted photo-
fibroblast growth factor, hepatocyte growth factor, and crosslinkable hydrogels for bone and
platelet-derived growth factor have been used for the cartilage regeneration
modulation of vessel formation [65,66] . For delivering drugs
or therapeutic agents to bone sites, various approaches Over the last decade, there has been immense progress in
have been investigated, such as nanoparticles, nanofibers, 3D bioprinting skeletal systems using photo-crosslinkable
and films. Among them, hydrogel attracts much attention hydrogels. In this part, we review the applications of 3D
owing to its compatibility and hydrophilicity, and it can bioprinted photo-crosslinkable hydrogels for bone and
regulate release performance by controlling swelling or cartilage tissue engineering.
degradation . Photo-polymerized hydrogels have also 4.1. Bioprinted hydrogels in bone tissue
[67]
been used for localized drug delivery depots due to the engineering
in situ formation of hydrogels and the direct adhesion to
the targeted tissue. As a bulk reservoir, hydrogels allow Bone has a highly specialized structure with a
for encapsulation of cells, drugs or nanoparticles, and mineral matrix, multiple cells, and vascular networks.
provide physical support at bone lesion site. Reconstruction of large-scale bone defects remains
In a report by Kim et al., they fabricated challenging due to the lack of biomimetic architectural,
PEGDA/chondroitin sulfate-based hydrogels and studied bioactive factors, and functional vasculature. With the
them as biomineralizing 3D scaffolds . Chondroitin advance of 3D bioprinting, more complicated bionic
[68]
sulfate has negative charge on its sulfate group, so it 3D constructs could be bioprinted, with different cell
binds with charged ions such as calcium and phosphate types and growth factors with hydrogel for better bone
to form an osteogenically favorable microenvironment, regeneration to imitate the hierarchical structure and
which will induce the biomineralization and osteogenic function of natural bone. Cui et al. developed a mimetic
differentiation of stem cells. The results proved that the bone structure, with a hard mineral matrix, a soft organic
ion binding and distribution in hydrogel were related to matrix and vascularized networks (Figure 2A) . The
[70]
the concentration of chondroitin sulfate, and PEGDA/ structure was constructed through a dual 3D bioprinter
chondroitin sulfate-based hydrogels induced osteogenic including a Fused Deposition Modeling (FDM) and SLA
differentiation of stem cells in vitro. After transplanting 3D bioprinter, by alternately depositing cell-loaded GelMA
this hydrogel into a critically sized cranial defect model, hydrogel (hMSCs and HUVECs), and biodegradable
10% chondroitin sulfate hydrogel induced effective bone polylactide (PLA) (Figure 2Ai). This capillary structure
regeneration with the highest bone density. allows cells to evolve and expand uniformly in the 3D
In another study, Xin et al. prepared recombinant space during culture period (Figure 2Aii). Moreover,
human BMP-2 (rhBMP-2)-laden GelMA hydrogel to bioactive growth factors such as BMP-2 and VEGF
accelerate bone repair . rhBMP-2 can localize BMSCs peptides were added into the scaffold designs to further
[69]
to the site of bone injury, promoting proliferation, facilitate osteogenesis and angiogenesis. Results indicated
and osteogenic differentiation. Mesoporous bioglass that the 3D printed biomimetic bone constructs could
nanoparticles (MBGNs) were used to load rhBMP-2 by integrate with surrounding native bone tissue, showing an
grafting, and then it would photo-crosslink with GelMA excellent bone regeneration and significant angiogenesis
hydrogel (GelMA/MBGNs-rhBMP-2), where rhBMP-2 ability. This study also provides a feasible strategy for
could be controllably released at an early stage of bone the construction of a hierarchical structure with multiple
regeneration, and calcium/silicon ions in MBGNs would functions, thereby meeting the current challenges for
be released to keep promoting osteogenesis in a long large bone repair.

42 International Journal of Bioprinting (2021)–Volume 7, Issue 3