Department of Biomedical Engineering, The University of Texas, Austin, Texas, USA.
Department of Orthopaedic Trauma, US Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA.
J Biomed Mater Res A. 2021 Nov;109(11):2255-2268. doi: 10.1002/jbm.a.37210. Epub 2021 May 5.
The high incidence of osteomyelitis associated with critical-sized bone defects raises clinical challenges in fracture healing. Clinical use of antibiotic-loaded bone cement as an adjunct therapy is limited by incompatibility with many antimicrobials, sub-optimal release kinetics, and requirement of surgical removal. Furthermore, overuse of antibiotics can lead to bacterial modifications that increase efflux, decrease binding, or cause inactivation of the antibiotics. Herein, we compared the efficacy of gallium maltolate, a new metal-based antimicrobial, to gentamicin sulfate released from electrospun poly(lactic-co-glycolic) acid (PLGA) wraps in the treatment of osteomyelitis. In vitro evaluation demonstrated sustained release of each antimicrobial up to 14 days. A Kirby Bauer assay indicated that the gentamicin sulfate-loaded wrap inhibited the growth of osteomyelitis-derived isolates, comparable to the gentamicin sulfate powder control. In contrast, the gallium maltolate-loaded wrap did not inhibit bacteria growth. Subsequent microdilution assays indicated a lower than expected sensitivity of the osteomyelitis strain to the gallium maltolate with release concentrations below the threshold for bactericidal activity. A comparison of the selectivity indices indicated that gentamicin sulfate was less toxic and more efficacious than gallium maltolate. A pilot study in a contaminated femoral defect model confirmed that the sustained release of gentamicin sulfate from the electrospun wrap resulted in bacteria density reduction on the surrounding bone, muscle, and hardware below the threshold that impedes healing. Overall, these findings demonstrate the efficacy of a resorbable, antimicrobial wrap that can be used as an adjunct or stand-alone therapy for controlled release of antimicrobials in the treatment of osteomyelitis.
与临界骨缺损相关的骨髓炎发病率高，给骨折愈合带来了临床挑战。抗生素骨水泥作为辅助治疗的临床应用受到限制，原因是其与许多抗生素不相容、释放动力学不理想，以及需要手术切除。此外，抗生素的过度使用会导致细菌发生修饰，增加外排、降低结合或使抗生素失活。在此，我们比较了新型金属类抗菌剂甘氨酸螯合镓与聚乳酸-羟基乙酸共聚物（PLGA）包埋的硫酸庆大霉素在治疗骨髓炎方面的疗效。体外评价表明，每种抗菌剂的释放可持续至 14 天。Kirby Bauer 试验表明，载硫酸庆大霉素的包埋物抑制了骨髓炎分离株的生长，与硫酸庆大霉素粉末对照物相当。相比之下，载甘氨酸螯合镓的包埋物不能抑制细菌生长。随后的微量稀释试验表明，骨髓炎菌株对甘氨酸螯合镓的敏感性低于预期，释放浓度低于杀菌活性的阈值。选择性指数比较表明，硫酸庆大霉素的毒性低于甘氨酸螯合镓，疗效也优于甘氨酸螯合镓。在污染性股骨缺损模型的初步研究中证实，载硫酸庆大霉素的电纺包埋物的持续释放可使周围骨骼、肌肉和硬件上的细菌密度降低至阻碍愈合的阈值以下。总体而言，这些发现表明，可吸收的抗菌包埋物具有疗效，可作为辅助或独立疗法，用于控制骨髓炎治疗中抗生素的释放。
