title: A PEGylated fibrin-based wound dressing with antimicrobial and angiogenic activity.
abstract: Wounds sustained under battlefield conditions are considered to be contaminated and their initial treatment should focus on decreasing this contamination and thus reducing the possibility of infection. The early and aggressive administration of antimicrobial treatment starting with intervention on the battlefield has resulted in improved patient outcomes and is considered the standard of care. Chitosan microspheres (CSM) loaded with silver sulfadiazine (SSD) were developed via a novel water-in-oil emulsion technique to address this problem. The SSD-loaded spheres were porous with needle-like structures (attributed to SSD) that were evenly distributed over the spheres. The average particle size of the SSD-CSM was 125-180 μm with 76.50 ± 2.8% drug entrapment. As a potential new wound dressing with angiogenic activity SSD-CSM particles were impregnated in polyethylene glycol (PEGylated) fibrin gels. In vitro drug release studies showed that a burst release of 27.02% in 6h was achieved, with controlled release for 72 h, with an equilibrium concentration of 27.7% (70 μg). SSD-CSM-PEGylated fibrin gels were able to exhibit microbicidal activity at 125 and 100 μg ml(-1) against Staphylococcus aureus and Pseudomonas aeruginosa, respectively. The in vitro vasculogenic activity of this composite dressing was shown by seeding adipose-derived stem cells (ASC) in SSD-CSM-PEGylated fibrin gels. The ASC spontaneously formed microvascular tube-like structures without the addition of any exogenous factors. This provides a method for the extended release of an antimicrobial drug in a matrix that may provide an excellent cellular environment for revascularization of infected wounds.
authors.affiliation: United States Army Institute of Surgical Research, Fort Sam Houston, TX 78234, USA.
authors.forename: Shanmuganathan
authors.initials: S
authors.lastname: Seetharaman
authors.forename: Shanmugasundaram
authors.initials: S
authors.lastname: Natesan
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Stowers
authors.forename: Conor
authors.initials: C
authors.lastname: Mullens
authors.forename: David G
authors.initials: DG
authors.lastname: Baer
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Suggs
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Christy
mesh_terms: D000891:Anti-Infective Agents, Local / Q000737:chemistry* / Q000494:pharmacology; D001458:Bandages; D004337:Drug Carriers / Q000737:chemistry; D005337:Fibrin / Q000737:chemistry* / Q000378:metabolism; D005782:Gels / Q000737:chemistry; D006801:Humans; D008422:Materials Testing; D008826:Microbial Sensitivity Tests; D008863:Microspheres; D018919:Neovascularization, Physiologic; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012837:Silver Sulfadiazine / Q000737:chemistry* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000891:Anti-Infective Agents, Local; D004337:Drug Carriers; D005782:Gels; D011092:Polyethylene Glycols; D005337:Fibrin; D012837:Silver Sulfadiazine