Using Wild‐Type and Transgenic Rodent Models to Tackle Immunological Evaluation Challenges of Collagen‐Based Biomaterials

The immunotoxicological evaluation of collagen-based medical devices typically relies on wild-type rodent models, but interspecies differences may cause biases in immune response. To address this, we developed a human Type III collagen transgenic mouse model. In accordance with ISO/TS 10993-20 guidelines, we assessed the immunotoxicity of human collagen and recombinant/cell-engineered collagens (CCs) using this model, alongside wild-type controls. The full-length human COL3A1 gene was integrated into C57BL/6J mice, with expression confirmed through mRNA and peptide analysis. Mice were injected with human placental stromal protein (positive control), two recombinant humanized collagens (RC-1, RC-2), and CC. The experimental design adhered to GB/T 16886.20 (ISO 10993-20) and YY/T 1465 standards, with assessments including serum antibody detection at multiple timepoints (0-90 days) and terminal analyses at 30 and 90 days, focusing on splenic lymphocyte subsets and local tissue reactions. Results showed that transgenic mice had lower antibody levels compared to wild-type controls, with wild-type mice displaying significantly higher antibody responses at 60 days. These findings suggest altered immune recognition patterns in transgenic mice. The study also indicated that recombinant/CCs triggered only transient immune responses, with no sustained activation. This model provides new insights for refining immunoevaluation strategies for collagen-based materials.