新型多功能GO/HA基仿生材料的构建与性能研究

Nowadays, there are many difficulties in clinical practice of bone repair and regeneration because bone substitutes have some defects, such as poor mechanical, postoperative infections (pyogenic osteomyelitis) and complication. It is very urgent to fabricate novel multi-functional materials for the bore repair. This project focuses on the combination of bio-mimetic mineralization with the synthesis of a new type of multi-functional bone substitution material based on grapheme oxide(GO)/hydroxyapatite(HA) nanocomposites. Under the condition near biomineralization, GO/HA based thin films or hydrogel will be prepared through interface recognition, in situ induction, ion diffusion, etc. The effect of size, different weight of GO to HA and the addition of other bone component (such as Mg2+, CO32-) on the morphology, composition and microstructure of the obtained GO/HA based composite materials will be discussed. And the biocompatibility and mechanical properties of nanocomposites will be also investigated for evaluating their possibility as surface coating of implants and bone scaffolds. The antibacterial property, the load capacity of joint drugs (both hydrophobic and hydrophilic drugs, such as antitumor and antibiotic drugs) on products and controlled release behavior will be explored at the same time. The production of singlet oxygen and heat initiated by irradiation of near-infrared (NIR) will be studied too. The joint drugs in "single-capsule" are expected to prevent tumor from recurrence and complication after bone repair. It is very important to fabricate multi-functional bone repair materials for developing the new ways of bone implants and reducing patient pain.

目前，全世界骨替代材料远不能满足临床的要求，如机械性能欠佳、骨缺损和骨填充导致的深部感染等，使骨修复成为难题，急待攻克。因此，本项目以新型多功能氧化石墨烯（GO）/羟基磷灰石（HA）基骨修复材料的研发为目标，在更接近生物矿化的条件下，通过界面识别、原位诱导、离子扩散等方式，仿生制备GO/HA基（如GO/HA/多糖）薄膜或凝胶。考察GO的大小、含量以及骨骼中其它成分（如Mg2+，碳酸根离子等）对所制备材料的组成、形态、微结构的影响，探讨材料的生物相容性、力学性能，评价其作为骨修复材料的涂层或支架材料的可能性；同时研究其抗菌性、联合负载疏水、亲水性药物（如抗肿瘤药，抗生素等）及可控释放行为，考察其光致生热、光致单线态氧产生的能力，实现"单胶囊"多联用药，以预防和治疗骨填充后的肿瘤复发、炎症等。这对于开拓骨修复的新途径、减轻病人的痛苦等具有重要的意义。

随着高科技的飞速发展对新型材料的需求，特别是人类健康、包括各种临床对新材料的需求，使多功能纳米仿生复合材料的研究越来越受到人们的重视，成为当今化学、材料、 生物、医学等多学科相互交叉和渗透的前沿课题。目前，全世界骨替代材料远不能满足临床的要求，如机械性能欠佳、骨缺损、骨填充导致的深部感染以及骨肿瘤复发等，使骨修复成为难题，急待攻克。因此，本项目将氧化石墨烯（GO）的韧性、亲水亲油以及光热性质与羟基磷灰石（HA）良好的生物相容性、高的吸附性以及pH敏感性相结合，以新型多功能GO / HA基骨修复材料和响应型多功能药物载体的仿生研发为目标，在更接近生物矿化的条件下，通过界面识别、原位诱导、离子扩散等方式，仿生制备了以GO和HA为基本单元的植入兼治疗的纳米复合材料以及响应型多功能药物载体。考察了反应条件对所制备材料的组成、形态、微结构的影响，探讨了材料的生物相容性、力学性能。通过体外实验和（或）动物实验，研究了其作为仿生组织工程材料（涂层、支架和凝胶材料）以及响应型多功能药物载体（胶束、微囊和肿瘤表面的包围壳）的可能性，取得了良好的结果。所制备的纳米复合物可联合负载疏水、亲水性药物（如化疗药物、光敏剂、抗生素等），具有对环境敏感可控释放药物行为，而且其抗菌性、光致生热、光致单线态氧产生的能力较强，实现了“单胶囊”的多联用药，达到了协同抗肿瘤或抗炎作用，提高了治疗效果，可以防止骨修复后的肿瘤复发和并发症的产生。该项目研究对于开拓新型骨修复材料和响应型药物载体制备的新途径、发展多功能医用材料具有重要的意义。