Substrate surface characteristics such as roughness, wettability and particle density are well-known contributors of a substrate's overall osteogenic potential. These characteristics are known to regulate cell mechanics as well as induce changes in cell stiffness, cell adhesions, and cytoskeletal structure. Pro-osteogenic particles, such as hydroxyapatite, are often incorporated into a substrate to enhance the substrates osteogenic potential. However, it is unknown which substrate characteristic is the key regulator of osteogenesis. This is partly due to the lack of understanding of how these substrate surface characteristics are transduced by cells. In this study substrates composed of polycaprolactone (PCL) and carbonated hydroxyapatite particles (HAp) were synthesized. HAp concentration was varied, and a range of surface characteristics created. The effect of each substrate characteristic on osteoblastic differentiation was then examined. We found that, of the characteristics examined, only HAp density, and indeed a specific density (85 particles/cm2), significantly increased osteoblastic differentiation. Further, an increase in focal adhesion maturation and turnover was observed in cells cultured on this substrate. Moreover, β-catenin translocation from the membrane bound cell fraction to the nucleus was more rapid in cells on the 85 particle/cm2 substrate compared to cells on tissue culture polystyrene. Together, these data suggest that particle density is one pivotal factor in determining a substrates overall osteogenic potential. Additionally, the observed increase in osteoblastic differentiation is a at least partly the result of β-catenin translocation and transcriptional activity suggesting a β-catenin mediated mechanism by which substrate surface characteristics are transduced.

中文翻译：

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羟基磷灰石颗粒密度通过 β-连环蛋白易位调节成骨细胞分化

基质表面特性，例如粗糙度、润湿性和颗粒密度，是基质整体成骨潜力的众所周知的贡献者。众所周知，这些特征可以调节细胞力学，并诱导细胞刚度、细胞粘附和细胞骨架结构的变化。促成骨颗粒，例如羟基磷灰石，经常被掺入基质中以增强基质的成骨潜力。然而，尚不清楚哪种底物特征是成骨的关键调节剂。这部分是由于缺乏对细胞如何转导这些基质表面特征的了解。在这项研究中，合成了由聚己内酯 (PCL) 和碳酸羟基磷灰石颗粒 (HAp) 组成的基材。HAp 浓度不同，以及创建的一系列表面特征。然后检查每种底物特征对成骨细胞分化的影响。我们发现，在检查的特征中，只有 HAp 密度，实际上是比密度（85 个颗粒/平方厘米），显着增加了成骨细胞分化。此外，在该基质上培养的细胞中观察到粘着斑成熟和周转增加。此外，与组织培养聚苯乙烯上的细胞相比，在 85 粒子/cm2 基质上的细胞中，β-连环蛋白从膜结合细胞部分到细胞核的易位更快。总之，这些数据表明颗粒密度是确定基质整体成骨潜力的一个关键因素。此外，