In reconstructive surgery the use of prevascularized soft tissue equivalents is a promising approach for wound coverage of defects after tumor resection or trauma. However, in previous studies to generate soft tissue equivalents on collagen membranes, microcapillaries were restricted to superficial areas. In this study, to understand which factors were involved in the formation of these microcapillaries, the levels of the angiogenic factors vascular endothelial growth factor (VEGF), Interleukin‐8 (IL‐8), and basic fibroblast growth factor (bFGF) in the supernatants of the tissue equivalents were examined at various time points and conditions. Additionally, the influence of these factors on viability, proliferation, migration, and tube formation in monocultures compared to cocultures of fibroblast and endothelial cells was examined. The results showed that VEGF production was decreased in cocultures compared to fibroblast monocultures and the lowest VEGF levels were observed in endothelial cell monocultures. Additionally, the highest levels of IL‐8 were observed in cocultures compared to monocultures. Similar results were observed for bFGF with lowest levels seen within the first 24 hr and highest levels in cocultures. VEGF and IL‐8 were shown to promote endothelial cell viability, proliferation and migration and angiogenic parameters such as tube density, total tube length, and number of tube branches. Addition of VEGF and IL‐8 to cocultures resulted in accelerated and denser formation of capillary‐like structures. The results indicate that VEGF, IL‐8, and bFGF strongly influence cellular behavior of endothelial cells and this information should be useful in promoting the formation of microcapillary‐like structures in complex tissue equivalents.

中文翻译：

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细胞间通讯对生成复杂的多细胞预血管化组织等效物的影响。

在重建手术中，使用预血管化软组织等效物是在肿瘤切除或创伤后伤口覆盖缺损的有希望的方法。然而，在之前的研究中，在胶原膜上产生软组织等效物时，微毛细血管仅限于表面区域。在这项研究中，为了了解哪些因素参与了这些微毛细血管的形成，血管生成因子血管内皮生长因子 (VEGF)、白细胞介素-8 (IL-8) 和碱性成纤维细胞生长因子 (bFGF) 在在不同时间点和条件下检查组织等效物的上清液。此外，与成纤维细胞和内皮细胞的共培养相比，这些因素对单一培养中的活力、增殖、迁移和管形成的影响进行了检查。结果表明，与成纤维细胞单一培养物相比，共培养物中 VEGF 的产生降低，并且在内皮细胞单一培养物中观察到最低的 VEGF 水平。此外，与单一培养相比，在共培养中观察到最高水平的 IL-8。对 bFGF 观察到类似的结果，在第一个 24 小时内观察到最低水平，在共培养物中观察到最高水平。VEGF 和 IL-8 显示出促进内皮细胞活力、增殖和迁移以及血管生成参数，如管密度、总管长度和管分支数。向共培养物中添加 VEGF 和 IL-8 导致毛细血管样结构的形成加速和致密。结果表明，VEGF、IL-8、