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Treating Chronic Wound Infections with Genetically Modified Free Flaps

Ghali, S; Bhatt, KA; Dempsey, MP; Jones, DM; Singh, S; Arabi, S; ... Gurtner, GC; + view all (2009) Treating Chronic Wound Infections with Genetically Modified Free Flaps. Plastic and Reconstructive Surgery , 123 (4) 1157 - 1168.

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Abstract

Background: The success of antimicrobial therapy has been impaired by the emergence of resistant bacterial strains. Antimicrobial peptides are ubiquitous proteins that are part of the innate immune system and are successful against such antibiotic-resistant microorganisms. The authors have previously demonstrated the feasibility of protein delivery via microvascular free flap gene therapy and here they examine this approach for recalcitrant infections. Methods: The authors investigated the production of the human cathelicidin antimicrobial peptide-LL37, delivered by ex vivo transduction of the rodent superficial inferior epigastric free flap with Ad/CMV-LL37. The vascular permeabilizing agent vascular endothelial growth factor ( VEGF) was co-administered during ex vivo transduction with adenoviral vectors in an attempt to augment transduction efficiency. A rodent model of chronic wound/foreign body infection seeded with bioluminescent Staphylococcus aureus was used to assess the biological efficacy of delivering therapeutic antimicrobial genes using this technology. Results: The authors were successful in demonstrating significant LL37 expression, which persisted for 14 days after ex vivo transduction with Ad/CMV-LL37. Transduction efficiency was significantly improved with the co-administration of 5 mu g of VEGF during transduction without significantly increasing systemic dissemination of adenovirus or systemic toxicity. They were able to demonstrate in the rodent model of chronic wound/foreign body infections a significant reduction in bacterial loads from infected catheters following transduction with Ad/CMV-LL37 and increased bacterial clearance. Conclusion: This study demonstrates for the first time that microbicidal gene therapy via microvascular free flaps is able to clear chronic infections such as occurs with osteomyelitis resulting from trauma or an infected foreign body. ( Plast. Reconstr. Surg. 123: 1157, 2009.)

Type:Article
Title:Treating Chronic Wound Infections with Genetically Modified Free Flaps
Additional information:WoS ID: 000265669400003 Times Cited: 1ArticleEnglishGurtner, G. CStanford Univ, Sch Med, Dept Surg, Div Plast Surg, PSRL,GK-201,257 Campus Dr, Stanford, CA 94305 USACited References Count: 47440AGLIPPINCOTT WILLIAMS & WILKINS530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USAPHILADELPHIA
Keywords:ANTIBIOTIC LL-37/HCAP-18, CATHELICIDIN ANTIMICROBIAL PEPTIDE, CHRONIC OSTEOMYELITIS, ENDOTHELIAL GROWTH-FACTOR, EX-VIVO TRANSDUCTION, EXPRESSION, methods, microvascular free flaps, OPEN TIBIAL FRACTURES, STAPHYLOCOCCUS-AUREUS, TARGETED GENE-THERAPY
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of)

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