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International Journal of Bioprinting Bioprinted osteoarthritis scaffolds

If left untreated, these lesions often progress to degenerative explant models, bioreactors, organoids, organ-on-a-chip
conditions such as osteoarthritis (OA). The World Health platforms, and 3D-bioprinted constructs. 18
Organization (WHO) estimates that the global population Scaffold-free 3D culture systems simulate in vivo
affected by OA will approach 1 billion by 2030, placing a cell growth conditions without external matrices or
significant burden on healthcare systems and household supports. Co-culturing articular chondrocytes (ACs)
19
economies worldwide. Cellular senescence within OA- with mesenchymal stem cells and chitosan/hyaluronic
4
affected joints has been identified as a key contributor to acid nanoparticles has been reported to promote
disease pathogenesis. Increasing evidence demonstrates chondrogenic differentiation. However, these models
5,6
20
that senescence-associated changes occur in several are limited by high cultivation costs, short cell viability,
joint components, including cartilage, synovium, and and increased susceptibility to apoptosis. Scaffold-based
meniscus. Nevertheless, there remains a lack of suitable 3D models, developed to overcome the limitations of
7,8
models to investigate the relationship between cartilage scaffold-free systems provide a more physiologically
and OA progression. Developing cartilage aging models relevant tissue-like environment. These models support
is, therefore, essential for studying the pathogenesis and more native-like 3D cellular behaviors. Embedding
advancement of OA. chondrogenic factors into hydrogel matrices for cell
In recent decades, research has focused on elucidating encapsulation has been demonstrated to enhance
21
the mechanisms of chondrocyte senescence, identifying cartilage formation. Although several issues remain,
therapeutic agents, and optimizing treatment strategies using such as high cost, limited scalability, slow proliferation,
various experimental models-including animal models, 2D and challenges in standardization, continued refinement
cell cultures, and advanced 3D systems. Current animal is needed to improve model reliability.
9,10
models used to study chondrocyte senescence typically rely Explant models involve the in vitro culture of tissue
on natural aging or surgical interventions in combination samples excised from live organisms under sterile
with gene knockouts targeting anti-senescence pathways. conditions. For example, treating cartilage explants with
11
22
For example, histological analysis of 18-month-old interleukin-1β can induce chondrocyte senescence.
23
guinea pigs has revealed moderate to severe chondrocyte However, limitations include technical complexity,
senescence, characterized by significant reductions in inability to fully mimic the in vivo microenvironment,
proteoglycan and collagen content, closely mimicking and species-specific differences, all of which must be
12
human cartilage degeneration. Additionally, in Del1 addressed through technological and methodological
heterozygous (Del1+/−) mice, histological assessments advances. Bioreactors provide dynamic culture conditions
from 3 to 22 months of age displayed accelerated knee under tightly controlled parameters and have been used
cartilage degeneration due to impaired type II collagen to separate cartilage and bone units independently.
13
gene expression. However, despite their relevance, While promising, their application is hindered by high
animal models present several limitations, including long maintenance costs, operational complexity, and membrane
experimental durations and high costs, which restrict their contamination risks. 24
use in large-scale OA research. 14 Organoids, which are 3D structures derived from adult
In contrast, 2D models offer simplicity, convenience, and or pluripotent stem cells, have gained attention for their
high experimental control, and have been widely adopted ability to mimic real organ architecture and function.
across various research areas. For instance, hydrogen They offer advantages over traditional 2D cultures and
15
peroxide (H₂O₂) treatment has been reported to induce patient-derived explants in terms of structural fidelity
25
oxidative and inflammatory stress in rat chondrocytes, and genetic similarity. For instance, human periosteum-
promoting cellular senescence. Nevertheless, 2D systems derived cells have been demonstrated to self-assemble
16
fall short in recapitulating the biomechanical cues, as in vitro and form bone organoids capable of autonomous
26
well as the complex cell–cell and cell–matrix interactions regeneration upon transplantation into mice. Despite
present in native cartilage tissue. To address these rapid progress, organoids still only partially reproduce
17
limitations, 3D culture technologies have been developed native organ functions and are often limited in longevity
27,28
to more accurately mimic in vivo conditions. These models and physiological complexity.
retain the advantages of 2D systems while offering a Organ-on-a-chip systems combine microfluidics and
microenvironment that better preserves cellular phenotype 3D printing technologies to replicate the microarchitecture
and behavior. 3D culture models can be broadly categorized of organs on a chip. A human-induced pluripotent stem
29
into scaffold-free 3D cell cultures, scaffold-based systems, cells-derived osteochondral chip has been used to simulate

Volume 11 Issue 4 (2025) 190 doi: 10.36922/IJB025150136