模拟体液浸泡法评价柠檬酸钙的生物学特性

Simulated body fluid immersion method for assessing biological characteristics of calcium citrate

背景:柠檬酸钙本身的溶解性能优于磷酸钙、硫酸钙等其他钙生物材料,并且合成的柠檬酸钙致密性良好,在降解过程中可高效平稳释放钙离子,所以更适合用于骨折缺损的填充,为骨折愈合初期提供所需要的钙离子。目的:将天然生物矿化牡蛎壳和柠檬酸反应生成生物型柠檬酸钙生物材料,以期望在骨折愈合修复方面得到良好的应用。方法:通过球磨机粉碎天然生物矿化的牡蛎壳,再经研磨制备成适合粒径的牡蛎壳粉,与柠檬酸反应得到生物型柠檬酸钙,再经研磨,过筛,得到适宜大小的柠檬酸钙颗粒。应用X射线和FT-IR光谱研究材料的结构和组分,扫描电子显微镜观察材料的表面形态,模拟体液实验评价其生物特性。结果与结论:牡蛎壳粉末与饱和柠檬酸发生化学反应,转化生成了柠檬酸钙材料,并且晶体结构排列有序,形态紧密,晶体之间结合紧凑,具有一定的力学性能,这种结构也有利于延长材料的降解时间,平稳释放钙离子。柠檬酸钙在降解吸收过程中并未明显改变体液的pH值,整个pH值波动于7.20-7.46之间,对人体细胞的刺激性小。随着柠檬酸钙材料的逐渐降解,溶液中Ca2+浓度逐渐增大,且释放相对平缓,最终达到适宜成骨细胞增殖分化所需的胞外钙浓度,逐步稳定在7 mmol/L左右。表明以天然牡蛎壳为原料制备的柠檬酸钙具有优良的生物特性,作为人工骨材料具有天然的优越性。

BACKGROUND：Calcium citrate has a better solubility than calcium phosphate, calcium sulfate, and other calcium biomaterials. The synthetic calcium citrate has a good denseness, and stably releases calcium ions at a high efficiency during the degradation. Consequently, it may be more suitable for the fil ing of fracture defects, providing needed calcium ions for early fracture healing. OBJECTIVE：To prepare calcium citrate biomaterials with a novel formulation based on the natural bio-mineralized oyster shel s and citric acid so as to expect to get a good application in fracture healing repair. METHODS：Crushing, grinding, and chemical reaction methods were used for refinement. Particle size analyzer, X-ray diffraction, scanning electron microscope, and Fourier transform infrared spectroscopy were adopted for analysis of the size distribution, composition, mineral phases, and micro-morphology. Biological characteristics were evaluated through a simulated body fluid experiment. RESULTS AND CONCLUSION：Oyster shel powder was reacted with saturated citric acid to produce the calcium citrate material that had uniform crystal structure and compact bonding among crystal bodies, and exhibited a certain mechanical ability. The calcium citrate material had a good crystal structure that was conductive to prolong the degradation time. The calcium citrate released calcium ions slowly, and did not produce dramatic changes in the pH value （7.20-7.46） of the surrounding in the dissolution process. With the gradual degradation of calcium citrate materials, Ca2＋concentration in solution increased gradual y and stably, and ultimately achieved an appropriate concentration of 7 mmol/L, suitable for osteoblast proliferation and differentiation. Calcium citrate prepared using natural oyster shel has good biological properties, and exhibits a natural superiority to artificial bone materials.