Biomimetic hydrogel scaffolds for stimulating fibrotic responses: development of an in-vitro assay for implant material testing.

Introduction: The foreign body response (FBR) is a complex immune response that affects implant integration and function. Conventional Methodology: A 3D hydrogel model was co-cultured with human fibroblasts and macrophages to investigate immune responses to implant materials such as ceramic, titanium and steel. Cytokine expression and ECM remodelling were measured over a 14-day period to characterise material-specific responses. Results: The hydrogel model enabled a detailed analysis of the immune response to different materials. The material with the strongest fibrotic response was titanium, which resulted in a notable increase in collagen and TGF-β1 in M2 macrophage cultures. Furthermore, the emergence of IL-6 and IL-4 as prominent cytokine trends provided valuable insight into the inflammatory and regenerative response. Discussion: The model demonstrates that titanium exhibits a probable propensity for fibrosis, a finding that is corroborated by elevated TGF-β1 levels. IL-6 has been identified as a significant marker for inflammatory reactions. The results offer new perspectives for the development of patient-specific models, and future studies should include the comparison of fibroblasts from patients who have responded to implants with those who have not. Conclusion: The 3D hydrogel model offers a promising, cost-effective