Karataş Esra, Karasulu H Yeşim, Azizoğlu Gülçin Arslan, Öcal Gizem Kaftan, Armağan Güliz, Nizam Nejat, Özkaya Çiğdem Atalayın, Tezel Hüseyin
Department of Pharmaceutical Technology, Ege University, Faculty of Pharmacy, 35040, Bornova, İzmir, Turkey; Department of Pharmacy Services, Ege University, Atatürk Health Care Vocational School, 35040, Bornova, İzmir, Turkey.
Department of Pharmaceutical Technology, Ege University, Faculty of Pharmacy, 35040, Bornova, İzmir, Turkey.
Int J Pharm. 2025 Feb 10;670:125136. doi: 10.1016/j.ijpharm.2024.125136. Epub 2024 Dec 25.
Dental implants are widely used to treat edentulism, but the extended osseointegration period can increase infection risk, potentially causing peri-implantitis or implant failure. Bone morphogenetic proteins (BMPs), particularly BMP-2, show promise in bone regeneration but require stability and controlled release for effectiveness. This study developed dental implants coated with polycaprolactone (PCL) nanofibers loaded with BMP-2 and α-tocopherol. BMP-2 was encapsulated in chitosan nanoparticles (BMP-2-CNPs) with an efficiency of 76.5 ± 1.01 %, particle size of 234.6 ± 0.15 nm, polydispersity index (PDI) of 0.284, and zeta potential of 24.97 ± 0.06 mV. BMP-2-CNPs and α-tocopherol were incorporated into PCL nanofibers using electrospinning. SEM imaging confirmed uniform nanofiber coating on implants. BMP-2 release from BMP-2-CNPs lasted 5 days with a 99 % release rate, while BMP-2 release from PCL nanofibers extended to 35 days with a 70 % release rate. α-Tocopherol release was 60 % within 24 h, continuing up to 96 h. The specific surface area of coated implants was 0.591-0.601 m/g. WST-1 analysis showed over 85 % cell viability for both L929 fibroblasts and MC3T3-E1 osteoblasts after 24 and 72 h, with no cytotoxicity or increased inflammatory biomarkers TNF-α and IL-1β. MC3T3-E1 cells showed up to a 16-fold increase in Alkaline Phosphatase (ALP) activity after 7 and 14 days, and enhanced expression of Runx2, Osteocalcin (OCN), and Osteopontin (OPN) genes, confirmed by Western Blot. Increased biomineralization was observed via Alizarin Red staining. In conclusion, BMP-2-CNPs and α-tocopherol-loaded PCL nanofibers on dental implants are a promising strategy to accelerate osseointegration post-implantation.
牙种植体被广泛用于治疗牙列缺失，但延长的骨结合期会增加感染风险，可能导致种植体周围炎或种植失败。骨形态发生蛋白（BMPs），尤其是BMP-2，在骨再生方面显示出前景，但需要稳定性和控释才能发挥效力。本研究开发了涂覆有负载BMP-2和α-生育酚的聚己内酯（PCL）纳米纤维的牙种植体。BMP-2被封装在壳聚糖纳米颗粒（BMP-2-CNPs）中，封装效率为76.5±1.01%，粒径为234.6±0.15nm，多分散指数（PDI）为0.284，zeta电位为24.97±0.06mV。使用静电纺丝将BMP-2-CNPs和α-生育酚掺入PCL纳米纤维中。扫描电子显微镜成像证实种植体上有均匀的纳米纤维涂层。BMP-2从BMP-2-CNPs的释放持续5天，释放率为99%，而BMP-2从PCL纳米纤维的释放延长至35天，释放率为70%。α-生育酚在24小时内释放60%，持续至96小时。涂覆种植体的比表面积为0.591 - 0.601m/g。WST-1分析显示，L929成纤维细胞和MC3T3-E1成骨细胞在24小时和72小时后细胞活力均超过85%，且无细胞毒性，炎症生物标志物TNF-α和IL-1β也未增加。MC3T3-E1细胞在7天和14天后碱性磷酸酶（ALP）活性最多增加16倍，Runx2、骨钙素（OCN）和骨桥蛋白（OPN）基因的表达增强，经蛋白质免疫印迹法证实。通过茜素红染色观察到生物矿化增加。总之，牙种植体上负载BMP-2-CNPs和α-生育酚的PCL纳米纤维是一种有前景的策略，可加速种植后骨结合。
