ALN定点修饰的PDD复合缓释系统在牙周内源性再生中的作用和机制研究

批准号:
82001096
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
高现灵
依托单位:
学科分类:
口腔颅颌面组织生物力学和生物材料
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
高现灵
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中文摘要
牙周缺损区破骨细胞过度增殖、干细胞数目减少和分化能力降低导致牙周组织再生困难。研制可募集干细胞和调节骨改建的生物材料是实现牙周内源性再生的关键。前期研究表明羟基磷灰石-甲基丙烯酸明胶支架可表面负载阿仑膦酸盐(ALN)进而抑制破骨细胞分化,但缺乏干细胞募集能力。进一步研究发现内含羟基磷灰石的部分脱矿牙本质(PDD)可缓释具有趋化活性的PDGF-BB,且具备内部负载ALN的潜力,据此推测利用PDD、ALN和甲基丙烯酸明胶构建复合缓释系统,可通过募集干细胞、诱导成骨和抑制破骨促进牙周内源性再生。本研究拟通过重结晶和光交联法制备缓释系统,测定ALN和生长因子的释放;体外探索该系统对干细胞的迁移和分化及对破骨细胞形成的作用;利用测序分析相关机制并体外验证;体内探讨该系统对干细胞募集和骨改建调节的影响,明确其在小型猪炎症性牙周缺损中的再生效果。旨在为牙周再生医学提供新的思路,为其临床转化提供理论基础。
英文摘要
The excessive proliferation of osteoclasts, the decreasing number and reduced osteogenic differentiation capacity of stem cells in periodontal defects lead to difficulty in periodontal regeneration. Thus, the development of a sustained-release system that could recruit stem cells and regulate bone remodeling plays a key role in periodontal regeneration. Our previous studies showed that alendronate-coated hydroxyapatite @ gelatin methacrylate scaffolds inhibited osteoclast formation, but lacked the ability to recruit stem cells. Further research found that partly demineralized dentin (PDD) containing hydroxyapatite could release chemotactic platelet-derived growth factor-BB (PDGF-BB), and had the potential to load ALN internally. Therefore, we believe that a new sustained-release system combining PDD, ALN and gelatin methacrylate could slowly release PDGF-BB and ALN, and promote periodontal endogenous regeneration by recruiting stem cells and regulating bone remodeling microenvironment. In this study, the sustained-release system was prepared by recrystallization and photo-crosslinking methods, then the release profiles of ALN and growth factors were dynamically determined. The in vitro effects of this system on the migration and differentiation of bone marrow mesenchymal stem cells, and on the formation of osteoclasts were investigated. The related mechanisms were explored by RNA-seq techniques and verify in vitro. The in vivo effects of this system on stem cell recruitment and bone remodeling were evaluated. The effect of this system on periodontal regeneration in minipig inflammatory periodontal defect models was clarified. This study aims to provide a new idea for periodontal regenerative medicine and provide a theoretical basis for the clinical translation.
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DOI:10.3877/cma.j.issn.1674⁃1366.2024.01.007
发表时间:2024
期刊:中华口腔医学研究杂志(电子版)
影响因子:--
作者:高现灵;龚启梅;林正梅
通讯作者:林正梅
牙本质改性抗菌水凝胶的构建及其在水平型牙周骨缺损修复中的作用研究
- 批准号:n/a
- 项目类别:省市级项目
- 资助金额:10.0万元
- 批准年份:2022
- 负责人:高现灵
- 依托单位:
国内基金
海外基金
