Construction and performance of exendin-4-loaded chitosan–PLGA microspheres for enhancing implant osseointegration in type 2 diabetic rats
Shaojie Shi,
Shuang Song,
Xiangdong Liu,
Guoqiang Zhao,
Feng Ding,
Wenshuang Zhao,
Sijia Zhang,
Yingliang Song,
Wei Ma
Affiliations
Shaojie Shi
Department of Oral Implants, School of Stomatology, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, The Fourth Military Medical University
Shuang Song
Department of Implant Dentistry, College of Stomatology, Xi'an Jiaotong University
Xiangdong Liu
Department of Oral Implants, School of Stomatology, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, The Fourth Military Medical University
Guoqiang Zhao
Department of Oral Implants, School of Stomatology, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, The Fourth Military Medical University
Feng Ding
Department of Oral Implants, School of Stomatology, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, The Fourth Military Medical University
Wenshuang Zhao
Department of Oral Implants, School of Stomatology, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, The Fourth Military Medical University
Sijia Zhang
Department of Oral Implants, School of Stomatology, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, The Fourth Military Medical University
Yingliang Song
Department of Oral Implants, School of Stomatology, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, The Fourth Military Medical University
Wei Ma
Department of Oral Implants, School of Stomatology, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, The Fourth Military Medical University
The updating and optimization of drug delivery systems is critical for better in vivo behaviors of drugs, as well as for improving impaired implant osseointegration in diabetes. Numerous studies have reported the benefits of exendin-4 on diabetic bone, with the potential to enhance osseointegration in diabetes. To construct an appropriate sustained-release system of exendin-4 targeting implant osseointegration in diabetes, this study fabricated exendin-4-loaded microspheres using poly(lactic-co-glycolic acid) (PLGA) and chitosan. The morphology, size, encapsulation efficiency, and drug release behavior of microspheres were investigated. The bioactivity of drug-loaded microspheres on cell proliferation and osteogenic differentiation of diabetic BMSCs was investigated to examine the pharmacologic action of exendin-4 loaded into chitosan–PLGA microspheres. Further, the influence of microspheres on osseointegration was evaluated using type 2 diabetes mellitus (T2DM) rat implant model. After 4 weeks, the samples were evaluated by radiological and histological analysis. The results of in vitro experiments showed that the prepared exendin-4-loaded chitosan–PLGA microspheres have good properties as a drug delivery system, and the chitosan could improve the encapsulation efficiency and drug release of PLGA microspheres. In addition, exendin-4-loaded microspheres could enhance the proliferation and osteogenic differentiation of diabetic BMSCs. The results of in vivo experiments showed the exendin-4-loaded microspheres significantly improved the impaired osseointegration and bone formation around implants in T2DM rats without affecting blood glucose levels. Thus, the local application of exendin-4-loaded chitosan–PLGA microspheres might be a promising therapeutic strategy for improving the efficacy of dental implants in T2DM individuals.
