气凝胶支架缓释金纳米棒促进颌骨缺损愈合的光热治疗研究

The reconstruction of jaw bone defects caused by trauma, inflammation and tumor remains an immerse challenge in oral and maxillofacial surgery. Recently, solar-thermal conversion materials, a nanomaterial with light-absorbing ability, have been used to heat up and promote the healing of bone trauma as a photothermal therapy. However, the shortage of time for its residence at the target region limited the application in clinic. Based on the previous researches, our team is plan to fabricate the artificial sustained-release aerogel construct which assembling the gold nanorods by electrospinning and freeze drying-shaping technology. By controlling the degradation rate of aerogels, we can delay the entry of gold nanorods into the bloodstream to anchor gold nanorods in the defect site and achieve a long-lasting photothermal effect. By detecting the expression of osteogenic-related proteins and mineral deposition, we aim to explore the effect of the localized surface plasmon resonance of precious metal on the osteogenic differentiation and mineralization of MSCs. Finally, we try to verify the effectiveness of photothermal therapy using the gold nanorods-released aerogels on the healing of mandibular defects by establishing the mandibular defect model of rabbit and regularly radiating with the Raman laser.

由创伤、炎症、肿瘤等原因造成的颌骨缺损的修复重建是口腔颌面外科的工作难点，纳米光热转换材料近年来被用于创伤光热治疗领域。但纳米光热转换材料在靶区域停留时间短制约了其在临床上的使用。本课题组在前期研究基础上，拟采用静电纺丝和冷冻干燥-成型技术制备具有金纳米棒缓释功能的气凝胶控释支架。通过控制可吸收支架的体内降解速度来延缓金纳米棒进入血液循环的时间，从而将金纳米棒锚定在骨缺损靶区域以达到一个长效的光热治疗效果。通过研究光热治疗过程中成骨分化相关蛋白的表达和矿物质的沉积，探讨贵金属局域表面等离子共振产热对骨髓基质干细胞成骨分化和矿化的影响。最后通过构建兔下颌骨缺损模型联合拉曼激光定期照射，验证气凝胶支架缓释金纳米棒光热治疗下颌骨缺损的有效性。

由创伤、炎症、肿瘤等原因造成的颌骨缺损的修复重建是口腔颌面外科的工作难点，纳米光热转换材料近年来被用于创伤光热治疗领域。本课题组在前期研究基础上，通过将金-钯纳米颗粒注射到大鼠骨缺损局部并辅以近红外激光照射，研究了金-钯纳米颗粒介导的光热治疗对于骨缺损愈合的影响。结果显示金-钯纳米颗粒介导的光热治疗可能通过WNT信号通路有效促进 MC3T3-E1细胞的体外增殖和成骨向分化、并加快了大鼠颅骨缺损的骨愈合。接着，为了探讨将纳米颗粒整合入气凝胶支架的可能性，我们运用静电纺丝技术将硅纳米颗粒负载到丝素纳米纤维中并证明整合有硅纳米颗粒的丝素气凝胶支架机械性能加强、并具有良好的骨诱导性。构建大鼠极限颅骨缺损并将负载有硅纳米颗粒的丝素气凝胶支架植入到缺损内，证明负载有硅纳米颗粒的丝素气凝胶支架能加速骨缺损愈合并有效升高骨分化标志的体内表达。