Shah Sarita R, Tatara Alexander M, Lam Johnny, Lu Steven, Scott David W, Bennett George N, van den Beucken Jeroen J J P, Jansen John A, Wong Mark E, Mikos Antonios G
Department of Bioengineering, Rice University, Houston, Texas 77030, United States.
Department of Statistics, Rice University, Houston, Texas 77251, United States.
ACS Biomater Sci Eng. 2016 Apr 11;2(4):558-566. doi: 10.1021/acsbiomaterials.5b00545. Epub 2016 Mar 24.
Antibiotic-releasing porous poly(methyl methacrylate) (PMMA) space maintainers, comprising PMMA with an aqueous porogen and a poly(DL-lactic--glycolic acid) (PLGA) antibiotic carrier, have been developed to facilitate local delivery of antibiotics and tissue integration. In this study, clindamycin-loaded space maintainers were used to investigate the effects of antibiotic release kinetics and dose upon bacterial clearance and bone and soft tissue healing in a pathogen-contaminated rabbit mandibular defect. Three formulations were fabricated for either high dose burst release (7 days) or with PLGA microparticles for extended release (28 days) at high and low dose. Although inoculated bacteria were not recovered from any specimens, the burst release formulation showed less inflammation and fibrous capsule formation and more bone formation close to the implant than the low dose extended release formulation by histologic analysis. These results suggest that local antibiotic release kinetics and dose affect soft and hard tissue healing independent from its ability to clear bacteria.
已开发出含抗生素的多孔聚甲基丙烯酸甲酯（PMMA）间隙保持器，其由带有水性致孔剂的PMMA和聚（DL-乳酸-乙醇酸）（PLGA）抗生素载体组成，以促进抗生素的局部递送和组织整合。在本研究中，使用负载克林霉素的间隙保持器来研究抗生素释放动力学和剂量对病原体污染的兔下颌骨缺损中细菌清除以及骨和软组织愈合的影响。制备了三种制剂，分别用于高剂量突释（7天）或用于高剂量和低剂量的延长释放（28天）的PLGA微粒。尽管未从任何标本中回收接种的细菌，但通过组织学分析，突释制剂比低剂量延长释放制剂显示出更少的炎症和纤维囊形成，并且在植入物附近有更多的骨形成。这些结果表明，局部抗生素释放动力学和剂量影响软组织和硬组织愈合，与其清除细菌的能力无关。
