From biofabrication to preclinical translation: a systematic review of animal models for 3D-bioprinted hydrogel strategies in hyaline cartilage repair

Background Hyaline cartilage has limited intrinsic regenerative capacity, making articular defect repair a major clinical challenge. Three-dimensional (3D) bioprinting enables fabrication of hydrogel constructs with controlled architecture, composition, and cell distribution. Methods Orthotopic in vivo studies published between 2017 and 2025 evaluating 3D-bioprinted hydrogels for articular cartilage repair were reviewed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Biofabrication strategies, cellular components, animal models, regenerative outcomes, and risk of bias were analysed separately for chondral and osteochondral defects. Results Twenty-seven studies were included. Proteins and polysaccharides predominated. Extrusion-based bioprinting (EBB) was the most frequent technique, and bone marrow-derived mesenchymal stem cells (BMSCs) the predominant cell type. Small-animal models accounted for 70% of chondral and 94.1% of osteochondral studies. Histology was reported in all studies, whereas biomechanical outcomes were assessed in only 10% and 23.5%, respectively. Functional recovery was assessed in 11.8% of osteochondral studies, while subchondral bone outcomes were evaluated by micro-computed tomography (micro-CT) in 58.8%. Risk-of-bias assessment yielded predominantly unclear judgements for allocation concealment, random housing, caregiver and investigator blinding, and random outcome assessment. Conclusions 3D-bioprinted hydrogels show promise for articular cartilage repair. However, translation remains limited by heterogeneous designs, predominance of small-animal models, incomplete reporting, and insufficient biomechanical and functional validation. The translational potential of this article This review identifies key barriers to clinical translation, including reliance on small-animal models, incomplete reporting, and limited biomechanical and functional validation. Future strategies should integrate clinically relevant models, standardized outcomes, and manufacturing feasibility from early development.