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

therapy for symptom relief ; (2) microfracture surgery, a configuration, facilitating stress distribution through
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minimally invasive option for defects less than 2 cm² via enhanced deformability. Collagen type II reaches maximal
marrow stimulation ; (3) autologous or allogeneic grafts, concentration in the DZ, with vertically oriented fibrillar
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which are limited by insufficient tissue availability and bundles optimized for compressive load-bearing. The
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poor integration between the graft and host tissue ; and CCZ undergoes a compositional shift, replacing collagen
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(4) total knee joint arthroplasty (TKA), commonly used to type II with type X to establish a calcified matrix for
treat end-stage joint degeneration, but in younger patients osteochondral integration. This transition reverses
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associated with major drawbacks, including limited abruptly in the SCB, where collagen type I supersedes type
lifespan of the prosthesis, restricted physical function and X as the predominant isoform. While minimally expressed
the risk of future revision surgeries. 10-12 in the CCZ, collagen type I becomes the dominant organic
Currently, conventional treatments have proven constituent in the SCB, conferring structural rigidity and
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insufficient to achieve complete bone and cartilage tensile strength.
regeneration. In recent years, 3D-printed scaffolds have GAGs and proteoglycans increase progressively from
been increasingly utilized for in situ regeneration of joint the SZ to the DZ, peaking in the DZ. This gradient facilitates
defects. Considering the layered characteristics of articular water retention and hydrostatic pressure management,
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cartilage, 3D-printed hierarchical biomimetic scaffolds critical for load-bearing. Their levels drop sharply in the
have garnered significant attention. This paper aims to CCZ as the matrix undergoes mineralization.
review the recent advancements in gradient-manufactured Water content is the highest in the SZ, aiding
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strategies based on 3D printing, providing a novel approach lubrication and reducing friction. It decreases progressively
for cartilage repair.
through the MZ and DZ, where lower levels enhance
2. Natural gradient of osteochondral tissue structural strength. In the CCZ, water is nearly absent due
to the predominance of mineralized matrix.
Native articular cartilage is a complex hierarchical tissue Hydroxyapatite concentration increases steadily within
that transitions from a surface layer of hyaline cartilage, the CCZ, reaching its peak in the SCB. This gradient
continuing with calcified cartilage in the deep layer, then provides hardness and compressive strength to the
to the subchondral osseous layer. These layers account mineralized regions. 16
for 90%, 5%, and 5% of the total thickness, respectively.
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Each layer has a distinct composition, along with These gradient distributions ensure a seamless
different microenvironment and mechanical properties. mechanical and structural transition between cartilage and
This hierarchical structure enables the joint to bear bone, supporting the functional integrity of the joint.
loads and serves to distribute load, absorb shock, and
facilitate motion. 14 2.2. Biochemical gradient
The extracellular matrix (ECM) creates a specialized
From the surface of the articular cartilage to the microenvironment that supports tissue metabolism, repair,
subchondral bone, the structure is divided into several and growth, mediated by biomolecular factors such as
distinct layers: the superficial zone (SZ), middle zone transcription factors, cytokines, and signaling molecules.
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(MZ), deep zone (DZ), calcified cartilage zone (CCZ), Gene expression regulated by these factors varies across
and subchondral bone (SCB). These layers not only differ osteochondral layers, with zone-specific markers supporting
in depth but also exhibit gradient features in various the specialized functions of each region. Articular cartilage
aspects, including composition, biochemical properties, and subchondral bone exhibit distinct molecular biology
mechanical characteristics, and topography gradient. profiles that support their specialized functions. In the
SZ, key biomolecular factors such as aggrecan, collagen
2.1. Content gradient type II alpha-1 chain (COL2A1), and SOX9 display peak
Hierarchical compositional gradients emerge across expression levels. Aggrecan and COL2A1 are critical for
zones from the SZ to the SCB. Collagen types I/II/X, maintaining cartilage mechanical integrity, while SOX9
glycosaminoglycans (GAGs), proteoglycans, water, and regulates chondrocyte differentiation and maturation.
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hydroxyapatite demonstrate depth-dependent gradients, Moving to the MZ and DZ, these factors decrease, reflecting
with systematic redistribution patterns. 15 a shift from cartilage synthesis to mineralization processes.
In the SZ, collagen type II exhibits lower concentration Concurrently, bone morphogenetic protein-2 (BMP2) and
but forms densely packed, surface-parallel fibrillar collagen type X alpha-1 chain (COL10A1) are upregulated,
networks, providing shear resistance to the surface. driving chondrocyte differentiation into osteoblast-like
Progressing to the MZ, fibers adopt a loosely organized progenitors and promoting matrix calcification. Alkaline
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Volume 11 Issue 4 (2025) 5 doi: 10.36922/IJB025120100