Clinical evidence indicates the compromised application of titanium implants (TIs) in diabetics, associated with reactive oxygen species (ROS) overproduction at the bone-implant interface. Silk fibroin (SF) has displayed impressive biocompatibility in the application of biomedical material and optimal anti-diabetic effects in oriental medicine. We proposed that SF-coated titanium implants (STIs) could alleviate diabetes-induced compromised osteointegration, which has rarely been reported before. To confirm this hypothesis and explore the underlying mechanisms, rat osteoblasts cultured on 3-dimensional (3D) -printed titanium implants (TIs) and STIs were subjected to normal serum (NS), diabetic serum (DS), DS with N-acetyl-L-cysteine (a ROS inhibitor) or SN50 (an NF-κB inhibitor). An in vivo study was performed on diabetic sheep with TIs or STIs implanted into bone defects on the crista iliaca. The results demonstrated that ROS overproduction induced by diabetes lead to osteoblast dysfunctions and cellular apoptosis on the TI substrate, associated with the activation of an NF-κB signaling pathway in osteoblasts. Importantly, the STI substrate significantly attenuated ROS production and NF-κBp65 phosphorylation, thereby ameliorating the osteoblast biological dysfunctions. These results were further confirmed in vivo by the improved osteointegration of the STIs, as evidenced by Micro-CT and histological examinations compared with those of TIs. These results demonstrated that the ROS-mediated NF-κB signaling pathway played a crucial role in diabetes-induced implant destabilization. Importantly, the SF coating, as a promising material for biomaterial-engineering, markedly improved the clinical treatment effect of TIs under diabetic conditions, possibly associated with the suppression of the NF-κB pathway.

临床证据表明，钛植入物 (TI) 在糖尿病患者中的应用受到损害，这与骨-植入物界面处的活性氧 (ROS) 过量产生有关。丝素蛋白（SF）在生物医学材料的应用中表现出令人印象深刻的生物相容性，并在东方医学中具有最佳的抗糖尿病作用。我们提出 SF 涂层钛植入物 (STI) 可以缓解糖尿病引起的骨整合受损，这在以前很少报道。为了证实这一假设并探索潜在机制，在 3 维 (3D) 打印的钛植入物 (TI) 和 STI 上培养的大鼠成骨细胞接受了正常血清 (NS)、糖尿病血清 (DS)、带有 N-乙酰基的 DS。 L-半胱氨酸（一种 ROS 抑制剂）或 SN50（一种 NF-κB 抑制剂）。体内_研究是在患有 TI 或 STI 的糖尿病绵羊上进行的，这些绵羊植入髂嵴的骨缺损处。结果表明，糖尿病诱导的 ROS 过度产生导致成骨细胞功能障碍和 TI 底物上的细胞凋亡，这与成骨细胞中 NF-κB 信号通路的激活有关。重要的是，STI 底物显着减弱了 ROS 的产生和 NF-κBp65 磷酸化，从而改善了成骨细胞的生物学功能障碍。这些结果在体内得到了进一步证实通过改善 STI 的骨整合，与 TI 相比，Micro-CT 和组织学检查证明了这一点。这些结果表明，ROS介导的NF-κB信号通路在糖尿病诱导的植入物失稳中起关键作用。重要的是，SF 涂层作为一种很有前途的生物材料工程材料，显着提高了 TI 在糖尿病条件下的临床治疗效果，这可能与抑制 NF-κB 通路有关。