Chitosan (CS)-based hydroxyapatite (HA) composites have emerged as a novel strategy for promoting bone regeneration. Here nanophase HA/CS composite coated porous titanium implants (nCT) were fabricated and their biological behavior under diabetic conditions was investigated. We proposed that the focal adhesion kinase (FAK)-mediated BMP-2/Smad pathway played a role in mediating the promotive effect of nCTs on osteoblast adhesion and differentiation under diabetes-induced high reactive oxygen species (ROS) condition. To confirm the hypothesis, rat osteoblasts on bare titanium implants (Ti) and nCT were subjected to normal serum (NS), diabetic serum (DS), DS + NAC (a potent ROS inhibitor) and DS + cytochalasin D (an actin polymerization inhibitor). In vivo on diabetic sheep implanted with Ti or nCT showed that diabetes-induced ROS overproduction impaired osteoblast adhesion, evidenced by immunostaining of F-actin and vinculin and morphological observation through inhibition of FAK phosphorylation, which contributed to suppressed BMP-2-dependent Smad1/5/8 phosphorylation. nCT substrate reactivated the FAK-BMP-2/Smad pathway, thus reversing osteoblast dysfunction, which exerted a similar effect to NAC treatment on Ti. These effects were further confirmed by improved osteointegration within nCT in diabetic sheep, evidenced by micro-CT and histological examinations. Our study demonstrated that reactivation of the FAK-BMP-2/Smad pathway was involved in improving osteoblast adhesion and differentiation by nano-HA/CS composite coating, potentially directing biomaterial modification and biofunctionalization under diabetic conditions.

中文翻译：

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FAK介导的BMP-2 / Smad途径参与糖尿病条件下纳米HA /壳聚糖复合涂层钛植入物介导成骨细胞粘附和分化的过程。

基于壳聚糖（CS）的羟基磷灰石（HA）复合材料已经成为促进骨再生的新策略。本文制备了纳米相HA / CS复合涂层多孔钛植入物（nCT），并研究了其在糖尿病条件下的生物学行为。我们建议在糖尿病诱导的高活性氧（ROS）条件下，粘着斑激酶（FAK）介导的BMP-2 / Smad途径在介导nCTs对成骨细胞粘附和分化的促进作用中发挥作用。为了证实这一假设，对裸钛植入物（Ti）和nCT上的大鼠成骨细胞进行了正常血清（NS），糖尿病血清（DS），DS + NAC（一种有效的ROS抑制剂）和DS +细胞松弛素D（一种肌动蛋白聚合抑制剂）的实验。 ）。体内对植入Ti或nCT的糖尿病绵羊的研究表明，糖尿病引起的ROS过量生产会破坏成骨细胞粘附，这可以通过F-肌动蛋白和纽蛋白的免疫染色以及通过抑制FAK磷酸化的形态观察来证明，这有助于抑制BMP-2依赖性Smad1 / 5 / 8磷酸化。nCT底物重新激活了FAK-BMP-2 / Smad途径，从而逆转了成骨细胞功能障碍，这与NAC治疗Ti的作用相似。通过微CT和组织学检查证明，糖尿病绵羊nCT内骨整合的改善进一步证实了这些作用。我们的研究表明，FAK-BMP-2 / Smad途径的激活与纳米HA / CS复合涂层改善成骨细胞的粘附和分化有关，