具有可调荧光特性的单分散超小生物活性玻璃纳米体系构筑及干细胞行为调控和成像基础研究

It has become an attractive yet a very challenging topic in nanomedicine to develop biodegradable and highly biocompatible inorganic nanomaterials with multi-functionalities. The nano-size effects for biology and wide biomedical applications of conventional bioceramics nanomaterials are still not explored well due to their big size (usually above 200 nm) and poor monodispersity. In this proposal, a series of novel biodegradable ultra-small (10-100nm) and monodispersed sol-gel bioactive glass nanoparticles (BGNs) with stem cells imaging and differentiation mediation abilities are developed. More specifically, bioactive glasses nanoparticles with highly controlled ultra-small size, morphology and monodispersity are fabricated taking the advantage of amphipathic poly (siloxane) templating techniques. The highly tunable photoluminescent properties of BGNs and stem cells imaging are achieved by doping of rare-earth elements. The differentiation control of bone marrow stem cells is carried out through nanoscale effects and functional ions release. Also those needed to be investigated include the effects and mechanism of synthetic conditions on the nano-size and nanostructure of BGNs, the relationships between the composition, structure, and properties of the materials, and the influences and mechanism of the rare-earth doping on the nanostructure, biodegradability, ions releasing behavior, fluorescent emissions, cell uptake and cytotoxicity, stem cells differentiation control and imaging of the materials. In summary, this project aims at developing novel multifunctional bioactive nanomaterials for bone tissue repair and bio-imaging applications, which evokes new ideas for developing a diversity of biodegradable and functional inorganic nanoscale bioactive materials based on our theoretical understandings.

开发具有生物相容性好、可降解、多功能无机纳米生物材料是目前纳米医学研究的热点和难点。传统生物陶瓷纳米材料由于尺寸大（200nm以上）、单分散性差、功能单一限制其广泛的生物医学应用。本项目拟研发一系列可降解的，具有荧光成像、分化调控功能的新型单分散溶胶-凝胶生物活性玻璃纳米粒（BGN）。采用双亲性聚硅氧烷模板调制技术制备小尺寸（10-100nm）、形貌、单分散性高度可控的BGN，利用稀土元素掺杂实现材料可调光致发光和干细胞成像应用，通过纳米尺寸效应和功能离子释放调控骨髓干细胞分化行为；研究材料纳米尺寸和纳米结构的控制规律和机制，组成-结构-性能关系；深入研究稀土掺杂对材料结构、降解、离子释放、荧光发射、细胞摄入和毒性、干细胞分化调控和成像的影响规律和机理。本项目将研制出可用于高效骨修复和生物成像领域的新型生物材料，并为开发新型可降解功能纳米材料提供重要的理论基础。

开发具有生物相容性好、可降解、多功能无机纳米生物材料是目前纳米医学研究的热点和难点。传统生物陶瓷纳米材料由于尺寸大（200nm以上）、单分散性差阻碍其纳米生物响应的发挥，且功能单一限制其广泛的生物医学应用。本项目研发了一系列可降解的，具有细胞成像、成骨分化调控功能的新型单分散溶胶-凝胶生物活性玻璃纳米粒（BGN）；采用模版技术和乳化技术合成了小尺寸、单分散性高度可控的BGN，利用稀土元素掺杂实现材料可调荧光发射(400~700nm)和细胞成像应用; 通过表面改性装载miRNA实现对干细胞成骨分化的有效调控；发现BGN材料可以通过金属离子与基因配位作用实现对核酸基因的有效装载和细胞内递送，实现了BGN和基因协同促进骨组织再生；采用分子生物学技术弄清楚了BGN材料可以通过激活TGF-bata信号通路促进脂肪干细胞的成骨分化的生物学机制。本项目研制出可用于高效骨修复和生物成像领域的新型生物活性材料，并为开发新型可降解功能纳米生物活性材料提供新的研究思路。