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International Journal of Bioprinting 3D bioprinting techniques & hydrogels materials

printing to bypass the need for prior in vitro culture while and the vascular abundance of subchondral bone, the
preserving the dryness and homing ability of BMSCs. 209,210 reconstruction of damaged tissue persists as a significant
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Several studies have evaluated growth factor-loaded clinical conundrum. The innovative manufacturing
hydrogel scaffolds for 3D-printed osteochondral repair, process known as 3D printing offers numerous
indicating a potential future research direction. opportunities for advancing osteochondral tissue
engineering. Given the critical need for precision in
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3.3.5. Exosomes fabricating osteochondral scaffold structures, enhancing
Exosomes (exos) are extracellular vesicles secreted by print resolution stands out as a key technical challenge
cells, with a diameter of 40–160 nm. They are rich in a alongside considerations related to print speed and
variety of cytokines and growth factors and are often processing costs. Electrodynamic printing technology
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involved in intercellular communication. Exos derived is an innovative printing method, which has a superior
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from MSCs have been reported to accelerate cartilage and resolution compared to traditional printing technology.
subchondral bone regeneration; thus, the development However, limited research currently exists in this area.
of bioactive materials based on exos has broad clinical Future investigations into this technology are anticipated
application prospects. 212,213 Sun et al. loaded the exos of to fabricate scaffolds with improved osteochondral tissue
MSCs onto the upper layer of a double-layer 3D-printed properties. In situ 3D printing technology eliminates
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hydrogel scaffold, achieving a near-normal tissue repair the need for in vitro cell culture, reducing complexity
effect in a rabbit osteochondral injury model. Li et al. and the risk of cell contamination while enhancing repair
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combined decellularized ECM (dECM) and exos for the capabilities, making it another key focus for future research.
first time to construct a spatially biomimetic scaffold by
employing 3D printing technology; the dCEM is capable For multilayer scaffolds, mismatched strain poses a
of promoting cartilage and bone formation, BMSC significant challenge and may result in design failures if not
seeding, and the continuous release of exos, effectively appropriately addressed. It is crucial to align the mechanical
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accelerating osteochondral regeneration in rat models. properties across layers for enhanced bonding strength. 4,222
Moreover, several studies have demonstrated that specific However, the current literature lacks comprehensive
vesicle subtypes encompass complete mitochondria studies on this aspect. Furthermore, natural osteochondral
or mitochondrial components, which can enhance the tissue exhibits an unevenly distributed porous structure,
functional status of target cells and restore mitochondrial which has been reported to promote the bidirectional
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function via mitochondrial transfer among cells. 216-218 differentiation of MSCs and osteochondral regeneration.
On this basis, Chen et al. fabricated an oriented scaffold Given these findings, focusing on gradient porosity
through 3D printing of exos derived from MSCs, GelMA structures could offer more promising avenues for future
hydrogels, and ECM, and the scaffold could ameliorate research. Besides its porosity, the two-layer structure of
mitochondrial dysfunction in chondrocytes, enhance bone cartilage also has distinct mechanical properties.
chondrocyte migration, and facilitate the polarization Substrate stiffness influences the migration of MSCs and
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of synovial macrophages to the M2 phenotype, which their differentiation into various cell types. Therefore,
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is beneficial for osteochondral tissue regeneration. the uneven mechanical distribution should be controlled
However, given the profusion of bioactive molecules in more precisely through 3D printing. One method involves
exos, the mechanism of osteogenesis and chondrogenesis printing gradient structures by altering the ratio of
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induced by exos remains ambiguous, and further studies hydrogels and bioactive nanomaterials in different layers ;
are required to validate this mechanism. The correlation the other method involves printing gradient structures by
between the exos release curve and the scaffold degradation patterning diverse bioinks or crosslinking densities. 224
rate merits optimization to determine the optimal effect on Recently, researchers have expressed significant interest
bone repair. Additionally, to increase their efficacy, exos in the 4D bioprinting of multifunctional bone scaffolds,
with targeted delivery functionality constitute a promising which incorporates time as the fourth dimension. Unlike
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research direction (Table 4). traditional 3D printing, scaffolds produced through 4D
technology exhibit predictable transformations over time
4. Conclusion and future perspectives concerning their form or functionality when subjected
Articular cartilage and subchondral bone constitute to specific external stimuli like pH levels or changes
unified functional units, and the notion of “osteochondral in humidity and temperature conditions. Notably,
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unit repair and regeneration” has endured for a it can furnish original-shaped osteochondral tissue
considerable period. Nevertheless, owing to the disparity scaffolds suitable for minimally invasive placement in
between ischemic and non-neurogenic hyaline cartilage host environments. Materials applicable for use in 4D

Volume 10 Issue 6 (2024) 81 doi: 10.36922/ijb.4472