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

way to regulate the degradation kinetics. For instance, defect site, providing insights into the material’s biological
incorporating HAp and β-TCP nanoparticles into performance over time. 47
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GelMA hydrogels can reduce the degradation rate for
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bone-phase scaffolds. Gao et al. improved the degradation 4.2. Interlaminar interface strength
performance of GelMA scaffolds by adding 1% HAp. In in vivo studies, mechanical stability is considered a
In vitro, phosphate-buffered saline (PBS) degradation critical factor for successful regeneration. Beyond the
tests showed that scaffolds without HAp exhibited more intrinsic mechanical properties of scaffolds, interface
than 70% weight loss after 4 weeks, while those with strength—another crucial element—plays a pivotal role in
ensuring the efficacy of the repair process. This encompasses
HAp degraded by only 50%. dECM can also retard the two key aspects: the strength of the interlaminar interface
degradation rate. Li et al. evaluated the residual mass (horizontal integration), and integration with native
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percentage and revealed a significant reduction in the tissue (lateral integration). 132
degradation rate with the addition of dECM. Bejarano
et al. reported that incorporating BG into the poly(D, During scaffold-based regeneration of osteochondral
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L-lactic acid) (PDLLA) polymer could accelerate the defects, the interface between the cartilage and bone
degradation rate while simultaneously maintaining the phases is prone to stress concentration due to the
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scaffold’s dimensional and structural integrity. discontinuity in their mechanical properties. Therefore,
tissue engineering scaffolds need to achieve an effective
Degradation kinetics of scaffolds are influenced by integration between cartilage and bone tissue.
their mesostructure, including factors such as porosity,
pore size, pore shape, grain size, and crystallinity. A higher However, bilayered or multilayered scaffolds are often
porosity generally leads to an increased degradation rate, ineffective in biomimicking osteochondral tissue due to
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as scaffolds with more micropores and a larger surface the potential for delamination between layers. Current
area facilitate the diffusion of degradation products, strategies for enhancing interlaminar interface strength
thereby accelerating the process. Larger pores also allow can be broadly categorized into the following approaches:
better penetration of degradation products and moisture, (1) interlamellar bonding, (2) mechanical interlocking
promoting cell growth and tissue infiltration, which further through contact surface topography design, (3) tissue
speeds up degradation. 127,128 Conversely, smaller grain sizes culture with cell seeding, and (4) specified 3D printing
reduce the degradation rate because they increase the grain techniques.
boundary area, hindering the diffusion of degradation Bonding is a traditional method to integrate two layers,
products and enhancing the material’s strength. 129 which can be achieved through chemical bonding or
solvent bonding. The dual-phase interface can be modified
The inflammatory microenvironment, including
cytokines and enzymes, can significantly influence the by introducing reactive group-containing agents that form
chemical bonds between components and the biopolymer
degradation rate. In the microenvironment of OA, a matrix through chemical interactions. Coyle et al.
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wide range of enzymes and cytokines undergo significant developed a bilayer dECM-incorporated GelMA scaffold,
alterations. Notably, MMP families, which are capable of in which the double layers were chemically bonded
cleaving collagen type II, play a pivotal role in cartilage using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/
degradation. Liu et al. established a triple-layer scaffold N-hydroxysuccinimide (EDC/NHS) coupling. EDC
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consisting of BMSC-laden methacrylated HA (MeHA), activates the carboxyl groups on the GelMA hydrogels,
PCL, and KGN as the chondral layer, coated with a MeHA generating highly reactive O-acylisourea intermediates,
plus diclofenac sodium layer, and a PCL plus β-TCP which are stabilized by NHS. These intermediates then
osseous layer. MeHA, a rapidly degradable material, has react with primary amines on the second hydrogel layer,
a tunable degradation rate influenced by enzymes such as forming amide bonds and effectively conjugating the layers.
MMPs. MMP-sensitive MeHA allows for the modulation This method ensures strong covalent bonding, enhancing
of degradation rate and surface drug release in response to the structural integrity and interface compatibility of the
disease activity, such as inflammation in arthritis. composite material.
To estimate the degradation rate, weight loss is a Liuyun et al. designed a method for modifying nano-
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standard approach for in vitro studies, where scaffolds are HAp with the assistance of L-lysine, and incorporated
incubated in simulated body fluid or PBS for 12 weeks, the modified HAp into poly(lactic-co-glycolic acid)
and the remaining mass is measured periodically. 42,48,54,55 (PLGA) to fabricate nanocomposites. L-lysine bonds
In vivo, histological evaluation is commonly employed to to the HAp surface through the formation of a calcium-
monitor scaffold degradation and tissue formation at the carboxylate linkage between the calcium of HAp and

Volume 11 Issue 4 (2025) 16 doi: 10.36922/IJB025120100