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Sustained local delivery of insulin for potential improvement of peri-implant bone formation in diabetes

机译:持续局部输送胰岛素可潜在改善糖尿病的种植体周围骨形成

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Dental implantation is an effective standard treatment modality to restore missing teeth and maxillofacial defects. However, in diabetics there is an increased risk for implant failure due to impaired peri-implant osseous healing. Early topical insulin treatment was recently shown to normalize diabetic bone healing by rectifying impairments in osteoblastic activities. In this study, insulin/poly(lactic-co-glycolic acid) ( PLGA ) microspheres were prepared by a double-emulsion solvent evaporation method. Microspheres were then incorporated in fibrin gel to develop a local drug delivery system for diabetic patients requiring implant treatment. In vitro release of insulin from fibrin gel loaded with these microspheres was assessed, and sustained prolonged insulin release over 21 days ascertained. To assess the bioactivity of released insulin and determine whether slow release might improve impaired diabetic bone formation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), alkaline phosphatase (ALP) activity, mineralized nodule formation, and ELISA (enzyme-linked immunosorbent assay) assays were performed. The insulin released from the drug delivery system stimulated cell growth in previously inhibited cells, and ameliorated the impaired bone-forming ability of human MG-63 cells under high glucose conditions. Fibrin gel loaded with insulin/ PLGA microspheres shows potential for improving peri-implant bone formation in diabetic patients.
机译:种植牙是恢复缺牙和颌面部缺损的有效标准治疗方法。然而,在糖尿病患者中,由于植入物周围骨愈合不良而导致植入物失败的风险增加。最近显示,早期局部胰岛素治疗可通过纠正成骨细胞活性受损来使糖尿病骨愈合正常化。在这项研究中,胰岛素/聚乳酸-乙醇酸(PLGA)微球是通过双乳液溶剂蒸发法制备的。然后将微球体掺入纤维蛋白凝胶中,为需要植入治疗的糖尿病患者开发局部药物输送系统。评估了从负载有这些微球的纤维蛋白凝胶中胰岛素的体外释放,并确定了在21天内持续延长的胰岛素释放。为了评估释放的胰岛素的生物活性并确定缓释是否可以改善受损的糖尿病骨形成,3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物(MTT),碱性磷酸酶(ALP)的活性,进行矿化结节形成和ELISA(酶联免疫吸附测定)测定。从药物递送系统释放的胰岛素刺激了先前抑制的细胞的细胞生长,并改善了在高葡萄糖条件下人MG-63细胞的成骨能力受损。载有胰岛素/ PLGA微球的纤维蛋白凝胶显示出改善糖尿病患者植入物周围骨形成的潜力。

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