Ren E J, Guardia A, Shi T, Begeman P, Ren W, Vaidya R
Department of Orthopaedic Surgery, Detroit Medical Center, Detroit, MI 48201, United States of America.
Department of Biomedical Engineering, Wayne State University, Detroit, MI 48202, United States of America.
Biomed Mater. 2021 Feb 24;16(2):025019. doi: 10.1088/1748-605X/abd689.
A novel injectable polymeric dicalcium phosphate dehydrate (P-DCPD) cement was developed with superior mechanical strength and excellent cohesion. The purpose of this study was to assess the in vitro performance of P-DCPD loaded with vancomycin (VAN-P), tobramycin (TOB-P) and combination of both (VAN/TOB-P) (10%, w/w). There is a distinctive release profile between VAN and TOB. VAN-P showed decreased initial burst (<30% within 3 d) and sustained VAN release (76% in 28 d). In the presence of TOB (VAN/TOB-P), >90% of VAN was released within 3 d (p < 0.05). Slow and limited TOB release was observed both in TOB-P (<5%) and in TOB/VAN-P (<1%) over 28 d. Zone of inhibition (ZOI) of Staphylococcus aureus growth showed that eluents collected from VAN-P had stronger and longer ZOI (28 d) than that from TOB-P (14 d, p < 0.05). Direct contact of VAN-P, TOB-P and VAN/TOB-P cements displayed persistent and strong ZOI for >3 weeks. Interestingly, the cement residues (28 d after drug release) still maintained strong ZOI ability. P-DCPD with or without antibiotics loading were nontoxic and had no inferior impacts on the growth of osteoblastic MC3T3 cells. VAN-P and TOB-P were injectable. No significant influence on setting time was observed in both VAN-P (11.7 ± 1.9 min) and VAN/TOB-P (10.8 ± 1.5 min) as compared to control (12.2 ± 2.6 min). We propose that a distinctive release profile of VAN and TOB observed is mainly due to different distribution pattern of VAN and TOB within P-DCPD matrix. A limited release of TOB might be due to the incorporation of TOB inside the crystalline lattice of P-DCPD crystals. Our data supported that the bactericidal efficacy of antibiotics-loaded P-DCPD is not only depend on the amount and velocity of antibiotics released, but also probably more on the direct contact of attached bacteria on the degrading cement surface.
一种新型可注射的聚磷酸二钙二水合物（P-DCPD）骨水泥被研发出来，它具有卓越的机械强度和良好的黏附性。本研究的目的是评估负载万古霉素（VAN-P）、妥布霉素（TOB-P）以及两者组合（VAN/TOB-P，10%，w/w）的P-DCPD的体外性能。万古霉素和妥布霉素之间存在独特的释放曲线。VAN-P显示出初始突释减少（3天内<30%）以及万古霉素的持续释放（28天内释放76%）。在有妥布霉素存在的情况下（VAN/TOB-P），超过90%的万古霉素在3天内释放（p<0.05）。在TOB-P（<5%）和TOB/VAN-P（<1%）中，28天内均观察到妥布霉素缓慢且有限的释放。金黄色葡萄球菌生长的抑菌圈（ZOI）显示，从VAN-P收集的洗脱液的抑菌圈比从TOB-P收集的更强且持续时间更长（28天对14天，p<0.05）。VAN-P、TOB-P和VAN/TOB-P骨水泥的直接接触显示出持续且强烈的抑菌圈，持续超过3周。有趣的是，水泥残渣（药物释放28天后）仍保持较强的抑菌能力。负载或未负载抗生素的P-DCPD均无毒且对成骨MC3T3细胞的生长没有不良影响。VAN-P和TOB-P均可注射。与对照组（12.2±2.6分钟）相比，VAN-P（11.7±1.9分钟）和VAN/TOB-P（10.8±1.5分钟）的凝固时间均未观察到显著影响。我们认为观察到的万古霉素和妥布霉素独特的释放曲线主要是由于万古霉素和妥布霉素在P-DCPD基质中的不同分布模式。妥布霉素的有限释放可能是由于妥布霉素掺入到P-DCPD晶体的晶格中。我们的数据支持负载抗生素的P-DCPD的杀菌效果不仅取决于抗生素释放的量和速度，还可能更多地取决于附着在降解水泥表面的细菌之间的直接接触。
