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International Journal of Bioprinting 3D-printed scaffolds for osteochondral defect

the carboxylate group of L-lysine, thereby improving the Co-printing involves the simultaneous or sequential
interface compatibility between the HAp particles and the deposition of different materials within a single 3D printing
PLGA matrix. process, enabling the creation of complex, functional

Interlocking is a mechanical bonding method where structures, and interfaces. This requires 3D printers with
material surfaces engage through geometric features such multiple print heads, each capable of handling distinct
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as grooves, hooks, or ridges, thereby enhancing adhesion materials. Continuous 3D printing provides another
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and structural integrity without the need for adhesives approach to enhance the mechanical properties. In
or chemical bonding. 3D printing, as a high-precision continuous 3D printing, the print head deposits successive
manufacturing technique, is ideal for creating interlocking material layers without interruption, ensuring seamless
surfaces. When utilizing FDM or stereolithography (SLA) integration and smooth transitions between materials. This
to print materials with varying properties, interlocking method effectively eliminates the interface misalignment
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designs can be incorporated to strengthen the interlayer or gaps often seen in traditional layer-by-layer printing.
adhesion. According to the review by Nedrelow et al. 4.3. Scaffold-native tissue integration
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focusing on scaffold interface design, interlocking a robust The mechanical discontinuity at the scaffold-native tissue
3D-printed bone phase with a cartilage phase hydrogel interface significantly hinders integration. Yodmuang
is the most effective method for enhancing the interface et al. that interface strength before mechanical loading
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strength. Diloksumpan et al. created a bilayer scaffold with and shear stresses within the scaffold during loading are
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an interlocking interface design. The bone phase consisted key determinants of integration. Periodic axial forces
of a bone-biomimetic ceramic ink containing tricalcium of 1 and 6 N were applied to the scaffold to simulate
phosphate, nanohydroxyapatite, and a custom-synthesized the contact stress experienced by cartilage during daily
biodegradable poloxamer, while the cartilage phase was activities and their effects on scaffold–cartilage interface
composed of MEW-printed PCL microfibers and gelatin- integration were evaluated. The results indicated that
based hydrogel loaded with chondroprogenitor cells. 1 N loading resulted in poor integration between the
During printing, the PCL microfibers interlaced with scaffold and cartilage, whereas 6 N loading significantly
the ceramic matrix, protruding into the cartilage region. enhanced interface strength, demonstrating that higher
This spatially organized arrangement enabled mechanical loading intensity more effectively promotes integration.
interlocking between the bone and cartilage phases. This effect may be attributed to increased shear and
Compared to non-interlocking designs, the adhesion interface stresses, which facilitate scaffold–cartilage cell
strength between the composite hydrogel and ceramic adhesion and accelerate cell and matrix migration and
increased by over 6.5 times. The fiber within the ceramic proliferation. Moreover, high-intensity loading improves
scaffold enables more effective lateral constraint of the mechanical matching between the scaffold and cartilage;
hydrogel under axial compression, resulting in a stronger simulates physiological loading; and enhances cartilage
mechanical response. cell migration, ECM synthesis, and cross-linking. It also
Although interface strength can be enhanced through activates cellular mechanosensing pathways, promoting
bonding strategies, it remains inferior to that of native cell proliferation, differentiation, and exosome secretion.
mature bone-cartilage boundaries. Hence, using cell- However, the detailed mechanisms are not yet illustrated;
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laden materials to induce in situ regeneration at the defect hence, studies devoid of mechanical analysis may lack
site may offer a promising solution. Current scaffold translational relevance for clinical applications.
designs still suffer from uneven cell distribution. The Crosslinking of ECM between the scaffold and
inability to precisely control cell placement and spatial native tissue can enhance integration. Zhao et al.
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alignment often results in discrepancies in cell density, present a multifunctional scaffold loaded with lysyl
potentially compromising the efficacy of tissue repair. oxidase (LOX) plasmid DNA, exosomes, and manganese
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ECM secretion by cells may help to create a more dioxide nanoparticles (MnO NPs). LOX facilitates ECM
harmonious interface. Wang et al. designed a cell-based crosslinking, strengthening the mechanical bonding
2
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strategy to improve integration and transition between between the scaffold and tissue. Concurrently, MnO
cartilage and osseous layers by sandwiching a human NPs efficiently scavenge excess ROS at the injury site,
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umbilical cord mesenchymal stem cells (hUCMSCs) layer preventing ECM degradation and thereby potentiating the
between the constructs before suturing. Histological and crosslinking activity of LOX.
immunohistochemical analyses showed more uniform
ECM distribution in the cell-loaded constructs, while the Cell-laden scaffolds offer a promising way to enhance
control group exhibited V-shaped gaps at the interface due scaffold–tissue integration. Claramunt et al. developed a
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to a lack of cells and ECM. polyurethane meniscal scaffold coated with fibronectin. The

Volume 11 Issue 4 (2025) 17 doi: 10.36922/IJB025120100