血糖响应型、自律性靶向释药种植体改善2型糖尿病大鼠骨结合的研究

批准号:
81701031
项目类别:
青年科学基金项目
资助金额:
20.0 万元
负责人:
陈陶
依托单位:
学科分类:
H1508.口腔颅颌面组织生物力学和生物材料
结题年份:
2020
批准年份:
2017
项目状态:
已结题
项目参与者:
季平、黄元丁、许杰、付体伟、周鹏飞、王涵、木志翔、李帝泽
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中文摘要
鉴于糖尿病患者较常人更易缺牙的倾向、种植修复对该群体代谢状况的有利影响及大量2型糖尿病患者(T2DM)处于血糖控制不佳的临床常态,如何改善该群体种植初期骨结合不良、降低其种植失败风险成为当务之急。研究证实胰高血糖素样肽-1受体激动剂(GLP-1Ra)通过其特异性受体(GLP-1R)发挥促进成骨、抑制破骨的调控作用;同时项目前期证实GLP-1R亦存在于T2DM大鼠种植体周,提示该受体作为促进T2DM骨结合潜在靶标的可能性。本项目拟以T2DM种植初期骨结合不良的直接原因为切入点,基于GLP-1Ra对骨组织的双重调控作用,结合微流控乳液模板法及选择性激光熔融技术,创新性地构建血糖敏感型、自律性靶向释药种植体。经体内外实验验证该体系对负载蛋白的响应性控释效果,明确GLP-1Ra局部控释对T2DM骨结合的影响,进而阐明其作用的具体分子信号机制,为提高中、重度T2DM患者种植成功率提供新思路和新方法。
英文摘要
At present, China has the largest diabetes mellitus (DM) population around the world, and type 2 diabetes mellitus (T2DM) accounts for about 90%-95% of the total number of DM patients. Compared to the healthy population, diabetic patients have increased frequency of tooth loss. In recent years, dental implant has become the most ideal way to repair teeth. However, it has been confirmed that DM is associated with a relatively higher failure rate for implant and substantial risks. Therefore, DM has been considered as a relative contraindication for dental implantation. Recent studies have demonstrated that T2DM patients may benefit from functional oral reconstruction based on dental implants. In view of the large number of T2DM patients, high incidence of tooth loss in such patients and the benefits of dental implants for metabolic status of T2DM patients, how to improve the success rate of dental implants in medium and severe T2DM has become a research hotspot. In this study, we constructed a glucose-responsive, self-regulated bio-smart implant system by selective laser melting & 3D printing technology with microfluidic fabrication approach. Focusing on the shortcoming of poor osseointergration of dental implants in T2DM, this study was designed based on the novel hypothesis that glucagon-like peptide-1 receptor agonist (GLP-1 Ra) targeted regulates the relevant cells of peri-implant bone. Through in vitro and in vivo experiments, the present study is to investigate the influence of the implant system on BMSCs and its peri-implant osseointergration, and to elucidate the mechanism underlying the effects of local application of GLP-1Ra on peri-implant osseointergration. This study provides new ideas and novel strategies in order to increase the success rate of dental implants in medium and severe T2DM patients.
本项目鉴于糖尿病患者较常人更易缺牙的倾向、种植修复对该群体代谢状况的有利影响及大量2 型糖尿病患者(T2DM)处于血糖控制不佳的临床常态,探究了如何改善该群体种植初期骨结合不良、降低其种植失败风险。研究已证实,糖尿病患者种植体周围的骨结合是一个复杂且长久的过程,植体植入体内后,会经历体液附着,蛋白沉积,免疫细胞识别与激活,以及干细胞附着和成骨等多个愈合阶段,受到多种因素的级联调控。本项目以T2DM种植初期骨结合不良的原因为切入点,构建具有抗菌和促成骨功效的双离子(Sr2+和Ag+)独立控释种植体系以及负载BMP2和IL-10的血糖炎症双敏感型、自律性释药水凝胶,并构建构建了T2DM大鼠种植体周围炎模型,经体内实验分别验证了两个体系的抗菌及促进骨再生作用、对负载蛋白的响应性控释效果及促进骨缺损愈合作用。为了探究其对巨噬细胞的极化状态的调控机制,经体外试验验证了对巨噬细胞的抗炎诱导作用以及对成骨细胞的分化促进作用,阐明该体系通过调控巨噬细胞的极化状态进一步调控下游成骨前体细胞的粘附、伸展以及分化能力的生物级联调控作 用的具体分子信号机制,为提高中、重度T2DM患者种植成功率提供新思路和新方法。
期刊论文列表
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专利列表
DOI:10.1007/s00774-020-01101-5
发表时间:2020
期刊:Journal of Bone and Mineral Metabolism
影响因子:--
作者:Yihan Li;Annie Shrestha;Hongmei Zhang;Lingjie Li;Dize Li;Tiwei Fu;Jinlin Song;Ping Ji;Yuanding Huang;Tao Chen
通讯作者:Tao Chen
Gelatin Nanoparticle-Injectable Platelet-Rich Fibrin Double Network Hydrogels with Local Adaptability and Bioactivity for Enhanced Osteogenesis
具有局部适应性和增强成骨作用的生物活性的明胶纳米颗粒注射富含血小板纤维蛋白双网络水凝胶
DOI:10.1002/adhm.201901469
发表时间:2020-01-29
期刊:ADVANCED HEALTHCARE MATERIALS
影响因子:10
作者:Mu, Zhixiang;Chen, Kaiwen;Chen, Tao
通讯作者:Chen, Tao
Strontium Ranelate Incorporated Enzyme-Cross-Linked Gelatin Nanoparticle/Silk Fibroin Aerogel for Osteogenesis in OVX-Induced Osteoporosis
雷尼酸锶掺入酶交联明胶纳米颗粒/丝素蛋白气凝胶用于 OVX 诱导的骨质疏松症的成骨
DOI:10.1021/acsbiomaterials.8b01298
发表时间:2019-03-01
期刊:ACS BIOMATERIALS SCIENCE & ENGINEERING
影响因子:5.8
作者:Li, Dize;Chen, Kaiwen;Ji, Ping
通讯作者:Ji, Ping
Comparison of in-situ bone ring technique and tent-pole technique for horizontally deficient alveolar ridge in the anterior maxilla
原位骨环技术与帐篷杆技术治疗上颌前牙槽嵴水平缺损的比较
DOI:10.1111/cid.12887
发表时间:2020-02-05
期刊:CLINICAL IMPLANT DENTISTRY AND RELATED RESEARCH
影响因子:3.6
作者:Yuan, Shuai;Mu, Zhixiang;Chen, Tao
通讯作者:Chen, Tao
Entanglement-Driven Adhesion, Self-Healing, and High Stretchability of Double-Network PEG-Based Hydrogels
双网络 PEG 水凝胶的缠结驱动粘附、自修复和高拉伸性
DOI:10.1021/acsami.9b14348
发表时间:2019-10-09
期刊:ACS APPLIED MATERIALS & INTERFACES
影响因子:9.5
作者:Chen, Kaiwen;Fen, Yangyingfan;Wang, Huanan
通讯作者:Wang, Huanan
Howship陷窝形貌促进成骨细胞微管去酪氨酸化推动破骨细胞骨架重塑的旁分泌机制研究
- 批准号:--
- 项目类别:省市级项目
- 资助金额:0.0万元
- 批准年份:2025
- 负责人:陈陶
- 依托单位:
代谢性疾病背景下PI的发病机制及防治策略研究
- 批准号:n/a
- 项目类别:省市级项目
- 资助金额:0.0万元
- 批准年份:2022
- 负责人:陈陶
- 依托单位:
基于MOF的2D“纳米盔甲”保护能量代谢核心-电子传递链抑制过度免疫应答在治疗糖尿病种植体周围炎中的作用机制研究
- 批准号:--
- 项目类别:--
- 资助金额:59万元
- 批准年份:2020
- 负责人:陈陶
- 依托单位:
国内基金
海外基金
