Center for Biomaterial Development and Berlin-Brandenburg Centre for Regenerative Therapies, Institute of Polymer Research, Helmholtz-Zentrum Geesthacht, Teltow, Germany.
Acta Biomater. 2012 Dec;8(12):4253-9. doi: 10.1016/j.actbio.2012.08.011. Epub 2012 Aug 16.
As the majority of the polymers used as cardiovascular grafts so far do not match the elasticity of human arteries (100-1000kPa) and the required endothelialization, a multifunctional material approach is needed to allow the adjustment of the mechanical properties while at the same time exhibiting a haemocompatible surface. Recently soft poly(n-butyl acrylate) networks (cPnBA) with adjustable mechanical properties were introduced as candidate materials with a surface that can be endothelialized. In this study, angiogenically stimulated intermediate CD163(+) monocytes/macrophages (aMO2) were utilized as a cellular cytokine release system to realize the functional endothelialization of the hydrophobic cPnBA surface. We investigated the influence of co-cultured aMO2 on the morphology, density and cytokine secretion of human umbilical venous endothelial cells (HUVEC) seeded on cPnBA with an elastic modulus of around 250kPa (cPnBA0250). A functional confluent HUVEC monolayer could be developed in the co-culture within 3days. In contrast, the HUVEC in the monoculture exhibited stress fibres, broadened marginal filament bands and significantly more and larger cell-free areas in the monolayer, indicating incomplete cell-substrate binding. Remarkably, a functional confluent monolayer formation could only be achieved in co-cultures; it did not develop with the sole supplementation of recombinant VEGF-A(165) to the HUVEC monocultures (unpublished data). The study demonstrated the multifunctional potential of cPnBA in combination with aMO2 as a cellular cytokine release system, adapting their secretion to the demand of HUVEC. In this way, a functional confluent monolayer could be generated within 3days.
由于迄今为止大多数用作心血管移植物的聚合物的弹性都与人体动脉(100-1000kPa)和所需的内皮化不匹配,因此需要采用多功能材料方法来调整机械性能,同时展现出具有血液相容性的表面。最近,具有可调节机械性能的软聚(正丁基丙烯酸酯)网络(cPnBA)作为候选材料被引入,其表面可内皮化。在这项研究中,促血管生成的中间 CD163(+)单核细胞/巨噬细胞(aMO2)被用作细胞细胞因子释放系统,以实现疏水性 cPnBA 表面的功能内皮化。我们研究了共培养的 aMO2 对弹性模量约为 250kPa(cPnBA0250)的 cPnBA 上接种的人脐静脉内皮细胞(HUVEC)形态、密度和细胞因子分泌的影响。在共培养物中,在 3 天内可以开发出功能完整的 HUVEC 单层。相比之下,在单核培养物中,HUVEC 表现出应激纤维、变宽的边缘丝带,以及单层中明显更多和更大的无细胞区域,表明细胞与基底的结合不完全。值得注意的是,仅在共培养物中才能实现功能完整的单层形成;而在单核培养物中仅补充重组 VEGF-A(165)则无法实现(未发表的数据)。该研究证明了 cPnBA 与 aMO2 结合作为细胞细胞因子释放系统的多功能潜力,可以根据 HUVEC 的需求来调节其分泌。通过这种方式,可以在 3 天内生成功能完整的单层。