Hassani Besheli Negar, Damoogh Sheyda, Zafar Bahareh, Mottaghitalab Fatemeh, Motasadizadeh Hamidreza, Rezaei Fatemeh, Shokrgozar Mohammad Ali, Farokhi Mehdi
School of Chemical Engineering, Collage of Engineering, University of Tehran, P.O. Box 11155-4563, Tehran 1417466191, Iran.
National Cell Bank of Iran, Pasteur Institute of Iran, P.O. Box 1316943551, Tehran 1316943551, Iran.
ACS Biomater Sci Eng. 2018 Aug 13;4(8):2836-2846. doi: 10.1021/acsbiomaterials.8b00149. Epub 2018 Jul 17.
One of the main challenges of using biomaterials for inducing bone regeneration is the bacterial resistance before complete bone repair. Biomaterials with both antibacterial and bone regeneration properties are more promising for bone repair. In the present study, vascular endothelial growth factor (VEGF) was loaded on silk fibroin nanoparticles (SFNPs) and then embedded in silk scaffold containing vancomycin to form a dual drug release system. The chemical and physical properties of the fabricated structure were confirmed by Fourier transform infrared, scanning electron microscopy, and ζ-potential analysis. The size of spherical SFNPs was ∼92 nm. The release kinetics of vancomycin and VEGF showed that ∼99.56% of vancomycin and ∼14% of VEGF were released during 21 and 28 days, respectively. The bioactivity of VEGF was ∼75%. Disk diffusion test confirmed the ability of this drug delivery system against methicillin-resistant (MRSA). Moreover, expression of the endothelial markers (FLK-1, vWF, and VE-cadherin), alkaline phosphatase, and matrix mineral production were higher in VEGF loaded groups. Taken together, the results indicated that the fabricated codelivery system was able to simultaneously deliver antibiotic and angiogenic factor, which can be considered as a potential candidate for the treatment of contaminated bone injuries.
使用生物材料诱导骨再生的主要挑战之一是在骨完全修复之前的细菌抗性。具有抗菌和骨再生特性的生物材料在骨修复方面更具前景。在本研究中，将血管内皮生长因子（VEGF）负载到丝素蛋白纳米颗粒（SFNPs）上，然后嵌入含有万古霉素的丝支架中，形成双药释放系统。通过傅里叶变换红外光谱、扫描电子显微镜和ζ电位分析证实了所制备结构的化学和物理性质。球形SFNPs的尺寸约为92nm。万古霉素和VEGF的释放动力学表明，在21天和28天内分别释放了约99.56%的万古霉素和约14%的VEGF。VEGF的生物活性约为75%。纸片扩散试验证实了该药物递送系统对耐甲氧西林金黄色葡萄球菌（MRSA）的抗菌能力。此外，在负载VEGF的组中，内皮标志物（FLK-1、vWF和VE-钙黏蛋白）、碱性磷酸酶的表达以及基质矿物质生成更高。综上所述，结果表明所制备的联合递送系统能够同时递送抗生素和血管生成因子，可被视为治疗污染性骨损伤的潜在候选物。
