生物陶瓷微颗粒引发的细胞和组织损害

Micro-particles of Bioceramics Could Cause Cell and Tissue Damage

为论证生物陶瓷烧结不完全形成的微颗粒（〈5μm）引发细胞和组织损害的假设，对该类颗粒在体内和体外的细胞和组织损害进行了研究：（1）对4种双相生物陶瓷（BCP）进行细胞毒性试验。试验发现所有的浸出液出现细胞毒性，但是浸出液经离心后，毒性消失；（2）对羟基磷灰石（HA）、p磷酸三钙（pTCP）和40％pTCP／60％HA混合物微颗粒进行细胞抑制实验。结果显示随着微颗粒的浓度增加，成纤维细胞活力下降；而当微颗粒浓度达到一万个／细胞时，细胞活力和增殖能力完全消失；（3）HA，pTCP和BCP陶瓷颗粒（500-1500um）被植入到兔子股骨远端，种植12周后β-TCP的降解率为40％，BCP为5％，但是HA接近不降解。新骨形成在β-TCP（21％）和HA（18％）比BCP（12％）更为明显。同时BCP颗粒的周围有很多的微颗粒形成，可见吞噬细胞吞噬微颗粒，形成吞噬体。以上结果提示，微颗粒可能是局部炎症和细胞损害的首要原因，而且有可能影响骨形成。因此，我们必须注意生物陶瓷烧结的重要性，它们的烧结不良就可形成微颗粒，引发细胞和组织的损害。特别是BCP陶瓷含有两种需要不同烧结温度的粉体，它的烧结难度较高，很易形成微颗粒。

We conducted studies to confirm the hypothesis that the cellular damage occurring around implanted biphasic bioceramics could be related to a micro-particles release because of an insufficient sintering. （1） An in vitro cytotoxicity study was performed on four biphasic ceramic （BCP） samples. Without the treatment of extraction medium, a cytotoxicity was observed, although after centrifugation this cytotoxicity disappeared in all samples. （2） Micro-particles of HA,β -TCP and 40%β-TCP/60%HA mixture were used for a cell inhibition study. A decrease of cell viability was observed with the increase in particles concentration. At 10000 particles/ cell, the viability and proliferation were completely inhibited. （3） HA, β-TCP and BCP ceramic granules were implanted in rabbit femoral cavities for 12 weeks. No degradation of HA granules was observed. The degradation was higher for β-TCP （40%） than for BCP （5%）. On the other hand, new bone formation was significantly higher for β-TCP （21%） and HA （18%） than for BCP （12%）. Much more micro-particles were formed around BCP granules than around β-TCP, and were phagocytosed by macrophages. The release of ceramic micro-particles could be related to the sintering process. BCP ceramics have to be sintered at only 1160℃. Consequently, HA microparticles of BCP ceramic are incompletely sintered and easily released after immersion or implantation. The microparticles could be at the origin of local inflammation and cell damage and could perhaps modify osteogenesis. Particular attention must be paid to this problem with regard to BCP ceramics because of the sintering difficulties of this bioceramic.