光固化丝素蛋白/硅酸盐生物活性陶瓷复合骨水泥的制备、优化和性能研究

Bone cements with controllable setting process, biocompatibility and bioactivity have significant application in hard tissue repairment. However, current bone cements with mono-component can hardly meet these requirements simultaneously. In the present program, we intend to combine a novel photocrosslinkable natural polymer--silk fibroin--with bioactive silicate bioceramics, which finally results in a serial of composite bone cements with the above mentioned multi-functions. Silicate bioceramics with different types, particle sizes and amount are incorporated into silk fibroin solution, respectively, to obtain silk fibroin/silicate bioceramic (SF/SiBioCer) composite bone cements with single or double network structures. Photocrosslinking process of each kind of composite bone cement is monitored to verify the feasibility of photocrosslinking of silk fibroin in the composite cements. Physicochemical properties including mechanical properties, behavior of ion release, degradability and ability to induce bone-like apatite mineralization are tested on each kind of composite bone cement to find out how fabrication parameters influence physicochemical properties. Thus, the optimal scheme can be provided for preparation of composite cements. Finally, the optimized composite bone cements are applied to bone regeneration by both in vitro and in vivo biological experiments. The present program will introduce a novel photocrosslinking system in the field of bone cements, which provides new ideas and references for preparation of multi-functional bone cements with controllable setting process, biocompatibility and bioactivity.

具有固化过程准确可控和生物相容性、生物活性良好的骨水泥材料在硬组织修复领域具有重要应用。然而，目前单一组分骨水泥难以同时满足上述多种性能要求。本项目拟将一种新颖的光固化天然生物材料丝素蛋白引入骨水泥领域，与具有良好生物活性的硅酸盐生物陶瓷结合，制备兼具固化过程准确可控、生物相容性和生物活性良好的复合骨水泥。通过改变硅酸盐生物陶瓷种类、粒径和含量等制备参数，获得具有单、双网络结构的丝素蛋白/硅酸盐生物活性陶瓷复合骨水泥，考察复合骨水泥体系中丝素蛋白光固化的可行性。研究复合骨水泥力学、离子释放、降解和诱导类骨磷灰石矿化等理化性能，揭示制备参数对复合骨水泥理化性能的影响规律，优化复合骨水泥的制备工艺。最后，评价优化的复合骨水泥体外和体内的成骨活性。本研究为骨水泥领域引入了一种新型光固化材料体系，对发展固化过程准确可控、并兼具生物相容性、生物活性的骨水泥提供新的思路和方法。

我国人口结构呈现逐步老龄化的趋势，这必然会伴随越来越多骨和牙齿等人体硬组织的疾病和损伤，对硬组织修复材料的需求将越来越多。骨水泥具有任意塑形、可注射和原位固化成型等特点，特别适用于复杂构造的缺损部位修复，目前临床上已经得到应用。丝素蛋白(SF)光固化材料最突出的特点是可自主控制交联反应的时间点、部位和固化程度，是一种准确可控的骨水泥固化形式。通过准确控制骨水泥的固化过程，可实现材料植入前性状稳定、植入后即刻固化的效果，避免因提前固化而失去可塑性、可注射性，或者因植入后病人移动、体液流动造成植入材料溃散。同时，丝素蛋白来源于天然高分子材料，原料与产物均具有良好的生物相容性，通过对丝素蛋白高分子链进行修饰，可以实现其光固化性能。本项目初步探究了影响丝素蛋白光固化的外界影响因素，给出了浓度、时间、光照强度与光固化行为之间的定性关系，并尝试在丝素蛋白分子链上通过化学改性，交联聚(L-丙交酯-乙交酯-ε-己内酯)以提高其力学性能；另一方面，本项目组制备了锶元素原位掺杂的硅酸二钙骨水泥和硅酸钙/磷酸镁复合骨水泥，对其结构、组成、理化及生物学性能进行了较系统的表征与评价，并初步研究了丝素蛋白/硅酸盐复合材料的光固化性能。该项目制备的锶掺杂的硅酸二钙骨水泥有望发展成为一种具有促进骨再生的自固化材料，硅酸钙/磷酸镁复合骨水泥具有作为某些承重部位骨修复的替代材料的潜能，用于骨缺损的修复。通过本项目的研究，项目组团队人员发表SCI收录论文9篇。