阳极氧化镁金属骨修复材料对骨肉瘤的抑制效应及其机制

Free radicals in the body relate to many illnesses including the osteosarcoma.H2 has the ability to scavenge free radicals, so it has the potential to treat these illnesses. Orthopedic Mg material is biodegradable in the body and H2 will be released during this process. The H2 releasing rate depends on the degradation rate, and the degradation rate of the Mg metal could be controlled by the surface structure of the metal. So it is possible to endow the Mg metal with the ability to inhibit osteosarcoma by designing its surface structure to control its H2 releasing rate and scavenge the free radicals at the implanting site. In this proposed study, Mg metal used for bony cavity repair after the osteosarcoma surgery will be subjected to anodic oxidation treatment to modify its surface structure, then the role of the surface structure on the metal degradation and H2 releasing rates will be studied, so as to realize the controlled H2 release in the biological environment. After that, the role of the dose and releasing rate of H2 on the free radical scavenging will be studied, so as to realize scavenging free radical under control. And then the inhibiting effects of H2 on the free radical expression in osteosarcoma cells, and the protecting effect on DNA structure of H2 will be studied, so as to explore the molecular biological effect of H2 released from Mg degradation. After that, the anti- osteosarcoma effect of Mg will be studied in the model animals. It is expected that Mg metal not only repairs the bony cavity after osteosarcoma surgery, but also inhibits the growth of osteosarcoma. It might have the potential to improve the survival rate for the osteosarcoma patient by the orthopedic Mg metal. It is also expected to explore the mechanism of the anti-osteosarcoma effect of Mg metal.

过剩自由基与包括骨肉瘤在内的多种疾病相关，氢具有清除自由基的功能，因此氢在防治这些疾病方面具有良好的前景；镁金属在生理环境下发生降解并析氢，析氢速率与降解速率相关，而其表面结构调控其降解速率，因此通过表面结构的设计实现镁金属的可控析氢及对自由基的可控清除，可能赋予镁金属以抑瘤性能。本项目采用阳极氧化手段对镁金属表面结构进行优化改性，研究表面结构对其在生理环境下的降解和析氢过程的影响规律，实现可控析氢；研究镁金属析氢量、析氢速率等因素对自由基清除作用的影响规律，实现对自由基的可控清除；考察镁金属析氢量、析氢速率对抑制骨肉瘤细胞表达自由基及保护其DNA结构的影响规律，揭示镁金属可控析氢所产生的分子生物学效应；采用骨肉瘤动物模型研究镁金属对组织细胞中的DNA的保护作用及其抑瘤效应，为同时实现修复骨肉瘤手术骨缺损腔的形态和功能并抑制骨肉瘤的扩散和转移奠定基础， 同时揭示其抑瘤效应的分子生物学机制。

自由基在肿瘤的发生和转移过程中发挥了重要的作用，氢气具有清除自由基的功能，镁金属在生理环境下降解析氢，因此镁金属材料具有应用于肿瘤预防和治疗的潜力。本项目采用碱热处理和阳极氧化方法对镁金属材料进行改性，实现了对镁金属降解和析氢过程的有效调控；并在Fenton反应体系、肿瘤细胞培养实验中有效清除了自由基；在大鼠动物模型中采用肿瘤细胞构建了肿瘤模型，植入镁金属后，肿瘤生长和转移受到抑制；通过检测动物体内的丙二醛水平，证实镁金属降解释放的氢气在动物体内具有清除自由基的作用。本项目研究结果证实镁金属材料具有抑制肿瘤生长和转移的能力，可能使镁金属材料在生物医学领域的应用获得进一步的扩展，不仅可实现对组织缺损的修复，同时可应用于包括肿瘤在内的与自由基相关疾病的预防和治疗。