Meyer Nima, Bax Daniel V, Beck Jochen, Cameron Ruth E, Best Serena M
Department of Materials Science and Metallurgy, University of Cambridge, Cambridge CB3 0FS, UK.
Geistlich Pharma AG, Product Development, Wolhusen, Switzerland.
Regen Biomater. 2023 Mar 10;10:rbad015. doi: 10.1093/rb/rbad015. eCollection 2023.
Collagen-based biomaterials are used widely as tissue engineering scaffolds because of their excellent bioactivity and their similarity to the natural ECM. The regeneration of healthy bone tissue requires simultaneous support for both osteoblasts and, where angiogenesis is intended, endothelial cells. Hence it is important to tailor carefully the biochemical and structural characteristics of the scaffold to suit the needs of each cell type. This work describes for the first time a systematic study to gain insight into the cell type-specific response of primary human osteoblast (hOBs) and human dermal microvascular endothelial cells (HDMECs) to insoluble collagen-based biomaterials. The behaviour was evaluated on both 2D films and 3D scaffolds, produced using freeze-drying. The collagen was cross-linked at various EDC/NHS concentrations and mono-cultured with hOBs and HDMECs to assess the effect of architectural features and scaffold stabilization on cell behaviour. It was observed that 3D scaffolds cross-linked at 30% of the standard conditions in literature offered an optimal combination of mechanical stiffness and cellular response for both cell types, although endothelial cells were more sensitive to the degree of cross-linking than hOBs. Architectural features have a time-dependent impact on the cell migration profile, with alignment being the most influential parameter overall.
基于胶原蛋白的生物材料因其出色的生物活性以及与天然细胞外基质的相似性而被广泛用作组织工程支架。健康骨组织的再生需要同时支持成骨细胞，以及在需要血管生成的情况下支持内皮细胞。因此，仔细调整支架的生化和结构特性以满足每种细胞类型的需求非常重要。这项工作首次描述了一项系统性研究，以深入了解原代人成骨细胞（hOBs）和人真皮微血管内皮细胞（HDMECs）对不溶性胶原蛋白基生物材料的细胞类型特异性反应。在使用冷冻干燥法制备的二维薄膜和三维支架上对细胞行为进行了评估。胶原蛋白在不同的1-乙基-3-(3-二甲基氨基丙基)碳二亚胺/ N-羟基琥珀酰亚胺（EDC/NHS）浓度下进行交联，并与hOBs和HDMECs进行单培养，以评估结构特征和支架稳定性对细胞行为的影响。结果发现，在文献标准条件的30%下交联的三维支架为两种细胞类型提供了机械刚度和细胞反应的最佳组合，尽管内皮细胞比hOBs对交联程度更敏感。结构特征对细胞迁移模式有时间依赖性影响，排列总体上是最具影响力的参数。
