Development of a chitosan-based wound dressing with improved hemostatic and antimicrobial properties.
Hemorrhage remains a leading cause of early death after trauma, and infectious complications in combat wounds continue to challenge caregivers. Although chitosan dressings have been developed to address these problems, they are not always effective in controlling bleeding or killing bacteria. We aimed to refine the chitosan dressing by incorporating a procoagulant (polyphosphate) and an antimicrobial (silver). Chitosan containing different amounts and types of polyphosphate polymers was fabricated, and their hemostatic efficacies evaluated in vitro. The optimal chitosan-polyphosphate formulation (ChiPP) accelerated blood clotting (p = 0.011), increased platelet adhesion (p=0.002), generated thrombin faster (p = 0.002), and absorbed more blood than chitosan (p < 0.001). Silver-loaded ChiPP exhibited significantly greater bactericidal activity than ChiPP in vitro, achieving a complete kill of Pseudomonas aeruginosa and a > 99.99% kill of Staphylococcus aureus consistently. The silver dressing also significantly reduced mortality from 90% to 14.3% in a P. aeruginosa wound infection model in mice. Although the dressing exerted severe cytotoxicity against cultured fibroblasts, wound healing was not inhibited. This study demonstrated for the first time, the application of polyphosphate as a hemostatic adjuvant, and developed a new chitosan-based composite with potent hemostatic and antimicrobial properties.
Ong
Shin-Yeu
SY
Combat Care Laboratory, Defence Medical and Environmental Research Institute, DSO National Laboratories, 27 Medical Drive #12-01, Singapore 117510.
Wu
Jian
J
Moochhala
Shabbir M
SM
Tan
Mui-Hong
MH
Lu
Jia
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D001458:Bandages; D001792:Blood Platelets / Q000166:cytology; D048271:Chitosan / Q000737:chemistry*; D006490:Hemostatics / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D010973:Platelet Adhesiveness / Q000187:drug effects; D012834:Silver / Q000737:chemistry; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects; D013552:Swine; D013917:Thrombin / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D006490:Hemostatics; D012834:Silver; D048271:Chitosan; D013917:Thrombin