新型复合壳聚糖季铵盐纳米粒子抗感染骨水泥的生物学特性

Biological property of a novel bone cement composited by quaternary ammonium salt chitosan nanoparticles

背景:全膝关节置换后假体周围感染一直是关节外科领域很难攻克的问题。对于肾功能不全的患者和抗生素的细菌耐药性问题,现有的抗生素骨水泥不能有效的解决。目的:研制由壳聚糖季铵盐纳米粒子复合制成,无肾脏毒性和无细菌耐药性的新型抗感染骨水泥。方法:实验分为3组,新型抗感染骨水泥组QCSNP-15,普通骨水泥组Palacos R,抗生素骨水泥组Palacos R+G。分别对各组骨水泥进行扫描电镜观察、骨水泥固化时间测定以及体外抗压强度试验;还进行了细胞毒性实验及体外抗菌实验。结果与结论:(1)扫描电镜结果:QCSNP-15材料表面有壳聚糖季铵盐纳米粒子分布;(2)固化时间:QCSNP-15长于抗生素骨水泥Palacos R+G;(3)抗压强度:QCSNP-15的抗压强度低于普通Palacos R骨水泥(P<0.05),但仍然大于ISO 5833所规定的70 MPa的标准;(4)材料表面细胞贴附性:MC3T3-E1成骨细胞在新型骨水泥QCSNP-15材料表面贴附良好,与抗生素骨水泥Palacos R+G细胞贴附结果类似,细胞伪足完全展开;(5)细胞毒性:3 h QCSNP-15成骨细胞贴附率低于抗生素骨水泥Palacos R+G(P<0.05);(6)材料的体外抗菌性:QCSNP-15具有与抗生素骨水泥Palacos R+G相近的抗菌活性,在PBS中浸泡2周后仍然具有一定的抗菌活性;(7)结果说明QCSNP-15具有与抗生素骨水泥相当的固化时间和优良的体外生物力学强度,无明显的细胞毒性,和有优良的体外抗菌活性。

BACKGROUND：Postoperative infection in patients underlying total knee arthroplasty is a long-standing puzzle. Current bone cement with antibiotics cannot effectively treat kidney function deficiency and bacterial resistance. OBJECTIVE：To develop a novel kind of bone cement prepared by quaternary ammonium salt chitosan nanoparticles. METHODS：There were three groups including QCSNP-15, Palacos R and Palacos R＋G groups. Morphology of the bone cement in each group was observed using scanning electron microscope, the setting time of bone cement was measured, and the in vitro compression strength, cytotoxicity and antibacterial activity tests were performed. RESULTS AND CONCLUSION：Scanning electron microscope observed that QCSNP-15 was made of quaternary ammonium salt chitosan nanoparticles and methyl methacrylate copolymer, and these nanoparticles distributed onto the material surface. The setting time of QCSNP-15 was longer than that of the Palacos R＋G bone cement. The compressive strength of QCSNP-15 was significantly lower than that of the Palacos R bone cement （P〈0.05）, but was larger than 70 MPa stipulated by ISO 5833. Osteoblasts MC3T3-E1adhered wel on the QCSNP-15, and pseudopodia ful y expanded. Similar findings were observed on the Palacos R＋G bone cement. The attachment rate of osteoblasts of the QCSNP-15 at 3 hours was significantly lower than that of the Palacos R＋G bone cement （P〈0.05）. The antibacterial activity did not significantly differ between QCSNP-15 and Palacos R＋G bone cements, even after 2-week immersion in the PBS. These findings suggest that QCSNP-15 exhibits appropriate setting time, good biomechanical property and antibacterial activity in vitro with no obvious cytotoxicity.