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

Niu et al. quantified depth-dependent mechanical (Figure 1): (1) composite gradient defined as
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gradients in rabbit articular cartilage, reporting Young’s methodologies that achieve stratified functionality through
modulus progression from the SZ (0.4–0.6 MPa) through layer-specific variations in material composition and
the MZ (0.6–1.0 MPa) to the DZ (2.0–3.0 MPa). This physicochemical properties; (2) microarchitectural gradient
mechanical gradient was corroborated in porcine cartilage characterized by the implementation of function-specific
by Sun et al., who documented analogous depth-related structural configurations across distinct layers to regulate
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variations with SZ (0.8 MPa), MZ (2.0 MPa), and DZ anisotropic mechanical or nutrient transport behaviors;
(3.6 MPa) Young’s modulus values. (3) biochemical gradient entailing spatio-temporal control
of biochemical factors within layered constructs to achieve
The mechanically vulnerable regions within
cartilage tissue also correspond to distinct histological zonal biological responses; and (4) cell heterogeneity
involving heterogeneous seed cell populations within
microstructural features. A distinct calcified cartilage discrete strata to emulate native tissue. Recent research
band, referred to as the “tidemark,” separates the DZ from efforts have focused on optimizing these hierarchical
the CCZ, marking the mineralization front of the calcified architectures, with key zone-specific fabrication approaches
cartilage. Continuous collagen fibrils pass through the systematically categorized in Table 2.
tidemark, hence serving as a transitional interface between
calcified and non-calcified cartilage and facilitating the 3.1. Composite gradient
gradual transition of tissue mineralization. The boundary Composite gradient architectures have become a
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between the CCZ and the SCB is demarcated by the predominant methodology for engineering scaffold
“cement line.” The absence of continuous collagenous hierarchical organization. This paradigm employs biphasic
connections between the CCZ and the SCB renders this or multiphasic systems integrating distinct biomaterials,
region biomechanically vulnerable. .Furthermore, the each engineered to address zone-specific mechanical
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pronounced stiffness changes between the CCZ and SCB are and functional demands. Typical designs incorporate
hypothesized to be a key factor underlying the delamination the following: (1) a bioactive, elastomeric, and porous
of cartilage from the bone, particularly under shear stress phase for chondral regeneration; and (2) a mechanically
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conditions. This steep variation in mechanical properties reinforced, slow-degrading phase replicating subchondral
creates localized stress concentrations, exacerbating the bone properties.
risk of tissue failure at the cartilage–bone interface. 36
Materials commonly used for the chondral layer
The progression of OA is characterized by progressive include natural biomaterials such as collagen, hyaluronic
reductions in both elastic modulus and stiffness of articular acid (HA), sodium alginate (SA), agarose, cellulose,
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cartilage. Emerging evidence suggests that early-stage and silk fibroin (SF). These natural materials provide an
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OA may involve biomechanical precursors, including optimal environment for cell adhesion, proliferation, and
stiffening of the DZ and diminished SCB stiffness, prior growth. However, their mechanical and physicochemical
to overt cartilage degeneration. Furthermore, the elastic properties may not always be sufficient for tissue
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modulus of cartilage demonstrates a significant correlation engineering applications, leading to the increased use
with OA severity grades. Quantitative analyses reveal of synthetic materials like polyethylene glycol (PEG),
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substantial mechanical degradation in advanced OA, polycaprolactone (PCL), polylactic acid (PLA), gelatin
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exemplified by the SZ Young’s modulus reduction from methacrylate (GelMA), and polyethylene glycol diacrylate
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26.51 ± 10.63 MPa in healthy cartilage to 18.58 ± 9.61 MPa (PEGDA). These synthetic materials can be modulated
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in severe OA specimens. Concurrently, both aggregate during the synthesis process to achieve desired properties.
modulus and shear modulus exhibit significant decreases Despite superb mechanical properties, they lack integrin-
in moderate-to-severe OA, particularly within the SZ and binding ligands, which limits direct interaction with cells.
MZ, indicative of compromised load-bearing capacity. 40
Ceramic materials, which are inorganic and non-
3. Hierarchy establishment strategies for metallic, are typically characterized by their superb
osteochondral regenerating scaffold hardness and brittleness. Notable ceramic materials used
for osteochondral regeneration include hydroxyapatite
Over the past decade, hierarchical 3D-printed scaffolds (HAp), biphasic calcium phosphate (BCP), tricalcium
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have emerged as a predominant strategy for osteochondral phosphate (TCP), and bioactive glass (BG). They
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regeneration. Advances in fabrication technologies have exhibit favorable biocompatibility and porosity, promoting
spurred the development of multiphase design strategies cell infiltration and tissue integration. Furthermore,
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to mimic zonal tissue complexity. Hierarchical 3D inorganic ions released by ceramic materials, such as
printing strategies are systematically categorized as follows silicon (Si), lithium (Li), and magnesium (Mg) ions, can
Volume 11 Issue 4 (2025) 7 doi: 10.36922/IJB025120100