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局部给予妥布霉素的可注射生物降解性聚氨酯支架。

Local delivery of tobramycin from injectable biodegradable polyurethane scaffolds.

机构信息

Department of Chemical Engineering, 2301 Vanderbilt Place, VU Station B #351604, Vanderbilt University, Nashville, TN 37235, USA.

出版信息

J Biomater Sci Polym Ed. 2010;21(1):95-112. doi: 10.1163/156856209X410256.

DOI:10.1163/156856209X410256
PMID:20040156
Abstract

Infections often compromise the healing of open fractures. While local antibiotic delivery from PMMA beads is an established clinical treatment of infected fractures, surgical removal of the beads is required before implanting a bone graft. A more ideal therapy would comprise a scaffold and antibiotic delivery system administered in one procedure. Biodegradable polyurethane (PUR) scaffolds have been shown in previous studies to promote new bone formation in vivo, but their potential to control infection through release of antibiotics has not been investigated. In this study, injectable PUR scaffolds incorporating tobramycin were prepared by reactive liquid molding. Scaffolds had compressive moduli of 15-115 kPa and porosities ranging from 85-93%. Tobramycin release was characterized by a 45-95% burst (tuned by the addition of PEG), followed by up to 2 weeks of sustained release, with total release 4-5-times greater than equivalent volumes of PMMA beads. Released tobramycin remained biologically active against Staphylococcus aureus, as verified by Kirby-Bauer assays. Similar results were observed for the antibiotics colistin and tigecycline. The versatility of the materials, as well as their potential for injection and controlled release, may present promising opportunities for new therapies for healing of infected wounds.

摘要

感染常影响开放性骨折的愈合。虽然聚甲基丙烯酸甲酯(PMMA)珠粒局部抗生素递送是治疗感染性骨折的既定临床治疗方法,但在植入骨移植物之前需要将珠粒取出。一种更理想的治疗方法将包括支架和抗生素递送系统,一次手术即可完成。在以前的研究中,已证明可生物降解的聚氨酯(PUR)支架在体内可促进新骨形成,但尚未研究其通过释放抗生素来控制感染的潜力。在这项研究中,通过反应性液体成型制备了含有妥布霉素的可注射 PUR 支架。支架的压缩模量为 15-115 kPa,孔隙率为 85-93%。妥布霉素的释放具有 45-95%的突释(通过添加 PEG 来调节),随后可持续释放长达 2 周,总释放量比同等体积的 PMMA 珠粒多 4-5 倍。释放的妥布霉素对金黄色葡萄球菌仍具有生物活性,这通过 Kirby-Bauer 测定得到了验证。对于抗生素多粘菌素和替加环素也观察到了类似的结果。这些材料的多功能性及其用于注射和控制释放的潜力,可能为治疗感染性伤口的新疗法带来了有希望的机会。

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