High-Concentration Type I Atelocollagen Enhances Early Cartilage Regeneration: An In Vivo Comparative Study

Background: Type I atelocollagen is used to treat full-thickness chondral lesions. However, evidence on the concentration-dependent effects of atelocollagen-based scaffolds on chondrogenesis is lacking. This study aimed to evaluate the in vitro and in vivo chondrogenic potentials of low-, intermediate-, and high-concentration atelocollagen-based scaffolds in a rabbit model of osteochondral defects. Methods: Human mesenchymal stem cells (hMSCs) were encapsulated in 3%, 6%, and 9% type I collagen gels to assess cell viability and chondrogenic differentiation in vitro. In vivo, full-thickness osteochondral defects (4 × 4 mm) were created in 24 rabbits and treated as follows: Group 1 (microfracture only), Group 2 (microfracture + 3% atelocollagen), Group 3 (microfracture + 6%), and Group 4 (microfracture + 9%). The animals were euthanized at 4, 8, or 12 weeks. Macroscopic and histological outcomes were evaluated using gross morphological assessment and modified O’Driscoll scores. Results: At 8 weeks postoperatively, Group 4 (7.17 ± 0.76) exhibited significantly higher macroscopic scores than Group 2 (3.83 ± 0.29, p < 0.001) and Group 3 (4.50 ± 0.50, p < 0.001), indicating near-complete defect filling and smooth surface restoration. At 12 weeks, Groups 2 (7.33 ± 0.58), 3 (7.50 ± 0.87), and 4 (8.00 ± 0.00) all demonstrated significantly higher macroscopic scores than Group 1 (0.17 ± 0.12, p < 0.001 for all). Histologically, all atelocollagen-treated groups (Group 2:20.77 ± 1.55; Group 3:23.5 ± 1.00; Group 4:23.67 ± 1.44) exhibited significantly higher scores than Group 1 (1.67 ± 0.29, p < 0.001), with Group 4 achieving the highest overall. Conclusion: High-concentration atelocollagen-based scaffolds significantly enhanced both the efficiency and quality of cartilage regeneration by providing mechanical support and a favorable microenvironment for chondrogenesis.