一种可注射生物活性磷酸钙骨修复材料的制备及表征

Preparation and characterization of an injectable bioactive calcium phosphate material for bone repair

背景:针对当前自体骨和异体骨移植治疗骨缺损存在的种种问题,急需研制生物活性可降解人工骨修复材料,特别是磷酸钙骨修复材料,目前依然是国内外研究的热点之一。目的:旨在开发一种磷酸四钙基可注射生物活性磷酸钙骨修复材料。方法:通过磷酸四钙基磷酸钙骨水泥原粉和无水磷酸氢钙以及不同组分固化液在室温下(25℃左右)混合制成可注射活性骨水泥,并通过X射线衍射,水泥硬度测定,在模拟体液中崩解以及溶血实验和细胞毒性实验等方法进行研究,探索其固体成分构成、液相构成、煅烧及干燥温度等条件对其物理性能、生物学性能的影响,从而筛选出一种或多种综合性能优异的骨修复材料。结果与结论:1煅烧温度低于1 300℃时,磷酸四钙产量很少,只有当温度接近1 400℃时,可以得到比较纯净的磷酸四钙;2极冷条件因避免了空气中水分的影响,得到大量纯净的磷酸四钙,而慢冷后的产物主要为羟基磷灰石,这说明极冷对于获得纯净的磷酸四钙至关重要;3随着液相中柠檬酸溶液比例的提高,骨水泥浸泡液中的p H值和溶血率逐渐增大,这说明柠檬酸溶液很容易导致溶血;4通过体外细胞实验证实,在液相选择上,NH_4/Na比为2∶1的磷酸氢铵和磷酸氢钠溶液构成的骨水泥溶血率最低,细胞生物相容性最好,最有利于细胞生长;51 400℃煅烧后过筛得到的粉体组成的骨水泥初凝时间最短,p H值影响最小,崩解性不高,溶血率最低,对细胞的抑制作用更小,这说明经过1 400℃煅烧,过筛粉体得到的骨水泥更加适合临床应用。

BACKGROUND： In view of the unavoidable problems of autogenous and allogenous bone grafts, it is an urgent need to develop biodegradable bone substitute materials, among which is calcium phosphate material that has become a hot spot in the domestic and foreign research.OBJECTIVE： To develop a biodegradable calcium phosphate material for bone repair based on tetracalcium phosphate（TTCP）. METHODS： The biodegradable calcium phosphate cement made from TTCP, dicalcium phosphate anhydrous and different constituents of curing liquids was prepared under room temperature（about 25 ℃）. The effects of solid components, liquid components as well as calcinations and drying temperature on the physical and biological performances were detected through X-ray diffraction test, hardness test, decay in a simulated body fluid, hemolysis and cytotoxicity tests, respectively, to select the bone repair material with excellent performances. RESULTS AND CONCLUSION： When the calcination temperature was lower than 1 300 ℃, TTCP was rarely available; only close to 1 400 ℃, the relatively pure TTCP was gained. A large number of pure TTCP were gained by rapid cooling because of avoidance of the moisture impact, but slow cooling made the main products to be hydroxyapatite, suggesting that rapid cooling is essential to obtain pure TTCP. With the increase of the proportion of citric acid solution in the liquid phase, the p H values and the hemolysis rate in the bone cement soak solution were increased gradually, illustrating that citric acid solution is easy to induce hemolysis. In vitro cell experiments showed that the hemolysis rate of bone cement with a solution of 2：1 NH_4/Na ratio was the lowest, and the biocompatibility was the best, which was the most favorable to cell growth. Cements was made of calcined powders sieved at 1 400 ℃ and showed the shortest initial setting time, least effect on p H values, lowest disintegration rate and hemolysis rate, and slightest inhibition effect on the cell proliferation, indicating that the bone cements made of sieved powder after 1 400 ℃ calcination is more suitable for clinical application.