Giano Michael C, Ibrahim Zuhaib, Medina Scott H, Sarhane Karim A, Christensen Joani M, Yamada Yuji, Brandacher Gerald, Schneider Joel P
1] Chemical Biology Laboratory, National Cancer Institute, National Institutes of Health Frederick, Frederick, Maryland 21701, USA [2] Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 197163, USA.
Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Nat Commun. 2014 Jun 24;5:4095. doi: 10.1038/ncomms5095.
Surgical site infections cause significant postoperative morbidity and increased healthcare costs. Bioadhesives used to fill surgical voids and support wound healing are typically devoid of antibacterial activity. Here we report novel syringe-injectable bioadhesive hydrogels with inherent antibacterial properties prepared from mixing polydextran aldehyde and branched polyethylenimine. These adhesives kill both Gram-negative and Gram-positive bacteria, while sparing human erythrocytes. An optimal composition of 2.5 wt% oxidized dextran and 6.9 wt% polyethylenimine sets within seconds forming a mechanically rigid (~1,700 Pa) gel offering a maximum adhesive stress of ~2.8 kPa. A murine infection model showed that the adhesive is capable of killing Streptococcus pyogenes introduced subcutaneously at the bioadhesive's surface, with minimal inflammatory response. The adhesive was also effective in a cecal ligation and puncture model, preventing sepsis and significantly improving survival. These bioadhesives represent novel, inherently antibacterial materials for wound-filling applications.
手术部位感染会导致显著的术后发病,并增加医疗成本。用于填充手术空隙和支持伤口愈合的生物粘合剂通常缺乏抗菌活性。在此,我们报告了一种新型的可注射生物粘合剂水凝胶,它由聚葡聚糖醛和支链聚乙烯亚胺混合制备而成,具有内在的抗菌特性。这些粘合剂能杀死革兰氏阴性菌和革兰氏阳性菌,同时不损伤人体红细胞。2.5重量%的氧化葡聚糖和6.9重量%的聚乙烯亚胺的最佳组合在几秒钟内就会凝固,形成一种机械刚性约为1700帕的凝胶,提供约2.8千帕的最大粘附应力。小鼠感染模型表明,这种粘合剂能够杀死在生物粘合剂表面皮下引入的化脓性链球菌,炎症反应最小。该粘合剂在盲肠结扎和穿刺模型中也有效,可预防败血症并显著提高存活率。这些生物粘合剂代表了用于伤口填充应用的新型、具有内在抗菌性能的材料。