Spoddig V J, Murkar Rasika S, Kopp Sascha, Walles Heike
Core Facility Tissue Engineering, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
Otto von Guericke Universität - Magdeburg, Experimentelle Thoraxchirurgie/Core Facility Tissue Engineering, Magdeburg, Germany.
Front Bioeng Biotechnol. 2025 Aug 29;13:1628630. doi: 10.3389/fbioe.2025.1628630. eCollection 2025.
The foreign body response (FBR) is a complex immune response that affects implant integration and function. Conventional models are limited by ethical and reproducibility issues, emphasising the necessity for reliable alternatives. The objective of this study was to develop a standardised test using a collagen hydrogel-based 3D co-culture system to simulate FBR.
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.
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.
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.
The 3D hydrogel model offers a promising, cost-effective alternative for studying FBR and allows for a more accurate analysis of immune responses to implants. Future studies should further investigate the interactions of fibroblasts and macrophages and compare the immune responses between different patient groups to better understand the mechanisms behind different responses.
异物反应（FBR）是一种复杂的免疫反应，会影响植入物的整合和功能。传统模型受到伦理和可重复性问题的限制，这凸显了可靠替代方案的必要性。本研究的目的是开发一种标准化测试，使用基于胶原蛋白水凝胶的3D共培养系统来模拟异物反应。
将3D水凝胶模型与人成纤维细胞和巨噬细胞共培养，以研究对陶瓷、钛和钢等植入材料的免疫反应。在14天的时间内测量细胞因子表达和细胞外基质重塑，以表征材料特异性反应。
水凝胶模型能够对不同材料的免疫反应进行详细分析。纤维化反应最强的材料是钛，这导致M2巨噬细胞培养物中胶原蛋白和转化生长因子-β1显著增加。此外，白细胞介素-6和白细胞介素-4作为突出的细胞因子趋势的出现，为炎症和再生反应提供了有价值的见解。
该模型表明钛表现出可能的纤维化倾向，这一发现得到了转化生长因子-β1水平升高的证实。白细胞介素-6已被确定为炎症反应的重要标志物。这些结果为开发针对特定患者的模型提供了新的视角，未来的研究应包括比较对植入物有反应的患者和成纤维细胞与无反应患者的成纤维细胞。
3D水凝胶模型为研究异物反应提供了一种有前景、具有成本效益的替代方法，并允许对植入物的免疫反应进行更准确的分析。未来的研究应进一步研究成纤维细胞和巨噬细胞的相互作用，并比较不同患者群体之间的免疫反应，以更好地理解不同反应背后的机制。
