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Updated: Jun 24, 2026

08:18
Engineered Vascularized Muscle Flap
Published on: January 11, 2016
Treating chronic wound infections with genetically modified free flaps.
Shadi Ghali1, Kirit A Bhatt, Marlese P Dempsey
1Stanford and San Diego, Calif.; and London, United Kingdom From the Department of Surgery, Division of Plastic Surgery, Stanford University School of Medicine, the Department of Plastic and Reconstructive Surgery, Royal Free Hospital, and the Division of Dermatology, University of California, San Diego.
Plastic and Reconstructive Surgery
|April 2, 2009
Summary
Gene therapy using microvascular free flaps successfully delivered antimicrobial peptides to clear chronic bacterial infections. This novel approach offers a promising strategy against antibiotic-resistant microorganisms.
Area of Science:
- Biomedical Engineering
- Infectious Diseases
- Gene Therapy
Background:
- Emergence of antibiotic-resistant bacteria necessitates novel therapeutic strategies.
- Antimicrobial peptides (AMPs) are crucial components of the innate immune system effective against resistant microbes.
- Previous work established protein delivery via microvascular free flap gene therapy.
Purpose of the Study:
- To investigate the efficacy of delivering the human cathelicidin antimicrobial peptide (LL37) using microvascular free flap gene therapy for recalcitrant infections.
- To enhance gene delivery efficiency using vascular endothelial growth factor (VEGF).
Main Methods:
- Ex vivo transduction of rodent superficial inferior epigastric free flaps with Ad/CMV-LL37.
- Co-administration of VEGF with adenoviral vectors to improve transduction.
- Assessment of biological efficacy in a rodent model of chronic wound/foreign body infection using bioluminescent Staphylococcus aureus.
Main Results:
- Sustained LL37 expression for 14 days post-transduction was achieved.
- VEGF co-administration significantly improved transduction efficiency without increasing toxicity or dissemination.
- Significant reduction in bacterial loads and enhanced bacterial clearance in infected catheters was observed.
Conclusions:
- Microvascular free flap gene therapy is a viable method for delivering antimicrobial peptides.
- This approach successfully cleared chronic infections in a preclinical model.
- This technology holds potential for treating infections like osteomyelitis associated with trauma or foreign bodies.

