纳米纤维双因子缓释微球——牙髓再生助力微平台

Regenerative Endodontics is a new way which tries to restore the dental pulp function. Dental pulp tissue engineering will take the place of root canal therapy in the future. Nano composite materials and technique of bioactive factors control-released provide the potential for the dental pulp regeneration. This study will prepare compound nano drug control-released system as a novel drug carrier by modification PLLA nanospheres with sodium alginate nano particles, in which platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) will be control released in order in nano microspheres and nano particles separately. The drug released curve will be mad and the proliferation and differentiation effect of the carriers on dental pulp stem cells (DPSCs) will be tested in vitro. In vivo, the subcutaneously injection model will be used to test the effect of the angiogenesis by using the carriers. Then, the complete dental pulp remove model of dogs will be set and used in observe the dental pulp regeneration. Histology method and micro CT will be used to assess the structure of regenerative to optimize the released dose and rate of the two bioactive factors. The study will provide both data for developing injectable double nano drug released system and potential of dental pulp regeneration in biological way.

牙髓病是口腔临床常见病，但是现行根管治疗术存在无法恢复牙髓生物功能的问题。文献和我们以往的研究工作表明，再生医学在牙髓病治疗中应用前景光明，左旋聚乳酸（PLLA）纳米纤维微球材料具有促进牙髓干细胞增殖、分化的作用，能促进原位血管化牙髓样组织的再生，因此，纳米微球支架结合生物因子缓释可能是实现牙髓再生的有效途径。本项目拟利用藻酸钠凝胶微粒修饰纳米微球，分别负载干细胞、碱性成纤维细胞生长因子（bFGF）和血小板源性生长因子（PDGF），研制可注射式藻酸钠/PLLA复合纳米微球支架材料，构建牙髓再生的微平台。通过体外双因子纳米微球控释效率和细胞增殖、分化实验检测复合微球材料和牙髓干细胞的生物相容性，利用裸鼠皮下注射模型和犬牙髓全切模型，从异位再生和原位再生两个层面观察双因子纳米微球控释系统对牙髓再生的作用。这些研究具有牙髓损伤修复与再生的理论意义和探索牙髓疾病生物治疗方法的临床应用价值。

牙髓病是口腔临床常见病，但是现行根管治疗术存在无法恢复牙髓生物功能的问题。文献和我们以往的研究工作表明，再生医学在牙髓病治疗中应用前景光明，纳米纤维微球材料具有促进牙髓干细胞增殖、分化的作用，能促进原位血管化牙髓样组织的再生，因此，纳米微球支架结合生物因子缓释可能是实现牙髓再生的有效途径。本项目利用改良双乳化法结合沉降法制备成功了双层缓释微球，分别负载碱性成纤维细胞生长因子（bFGF）和血小板源性生长因子（PDGF），混合牙髓干细胞后组成微球-细胞复合体，构建牙髓再生的微平台。通过体外双因子纳米微球控释效率和细胞增殖、分化实验检测复合微球材料和牙髓干细胞的生物相容性，利用裸鼠皮下注射模型从异位再生层面观察到了双因子纳米微球控释系统对牙髓再生的作用。这些研究具有牙髓损伤修复与再生的理论意义和探索牙髓疾病生物治疗方法的临床应用价值。