Collagen biomaterials are widely used for soft tissue augmentation. Cross‐linking techniques for collagen matrix (CM) achieve mechanical and volumetric stability; nevertheless, cross‐linking may compromise biocompatibility. The aim of the present study was to investigate two different three‐dimensional (3D) porcine‐derived CMs, noncross‐linked (ncl)_CM and cross‐linked (cl)_CM, for their effects on macrophages (Mφ) and gingival fibroblasts. The effects of the CMs on the cell viability, proliferation, and polarization of Mφ derived from human monocyte THP‐1 cells were assessed. The effects of paracrine factors from Mφ cultured on the CMs were further studied in human gingival fibroblasts (HGF‐1 cells). The spongy layer of ncl_CM was partially resorbed after 1 day of culture. cl_CM maintained increased numbers of viable cells when compared with ncl_CM on day 3 for both THP‐1 and HGF‐1 cells. Higher mRNA levels of M1 markers, including IL‐1 and IL‐6, were found in Mφ cultured on cl_CM, while no significant differences were observed in M2 marker expression levels, including Arg1 and CD206, for cells cultured on both CMs when compared with those of the control. Furthermore, the conditioned medium collected from Mφ cultured on both CMs decreased cell viability. Nevertheless, neither of the CM‐conditioned media influenced the mRNA levels of TGF‐β, COL1a2, and PDGF‐A in HGF‐1 cells when compared with the control media. A comparison showed that cl_CM tended to result in more viable cells than ncl_CM, while cl_CM polarized Mφ toward an M1 phenotype, which was confirmed by the observation of increased mRNA levels of pro‐inflammatory cytokines.

中文翻译：

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三维异种胶原基质上巨噬细胞极化和牙龈成纤维细胞行为的体外观察。

胶原生物材料广泛用于软组织填充。胶原基质（CM）的交联技术实现了机械和体积稳定性；然而，交联可能会损害生物相容性。本研究的目的是研究两种不同的三维 (3D) 猪衍生 CM，非交联 (ncl)_CM 和交联 (cl)_CM，对巨噬细胞 (Mφ) 和牙龈成纤维细胞的影响。评估了 CMs 对源自人单核细胞 THP-1 细胞的 Mφ 的细胞活力、增殖和极化的影响。在人牙龈成纤维细胞（HGF-1 细胞）中进一步研究了来自 Mφ 培养的旁分泌因子对 CM 的影响。ncl_CM 的海绵层在培养 1 天后部分吸收。与第 3 天的 ncl_CM 相比，对于 THP-1 和 HGF-1 细胞，cl_CM 保持了增加的活细胞数量。在 cl_CM 上培养的 Mφ 中发现了更高的 M1 标志物 mRNA 水平，包括 IL-1 和 IL-6，而与在两种 CMs 上培养的细胞相比，M2 标志物的表达水平（包括 Arg1 和 CD206）没有显着差异。那些控制。此外，从在两种 CM 上培养的 Mφ 收集的条件培养基降低了细胞活力。然而，与对照培养基相比，CM 条件培养基均不影响 HGF-1 细胞中 TGF-β、COL1a2 和 PDGF-A 的 mRNA 水平。比较表明 cl_CM 倾向于产生比 ncl_CM 更多的活细胞，而 cl_CM 将 Mφ 极化为 M1 表型，