title: Injectable bioadhesive hydrogels with innate antibacterial properties.
abstract: 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.
authors: 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.
authors: Michael C
authors: MC
authors: Giano
authors: Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors: Zuhaib
authors: Z
authors: Ibrahim
authors: Chemical Biology Laboratory, National Cancer Institute, National Institutes of Health Frederick, Frederick, Maryland 21701, USA.
authors: Scott H
authors: SH
authors: Medina
authors: Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors: Karim A
authors: KA
authors: Sarhane
authors: Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors: Joani M
authors: JM
authors: Christensen
authors: Chemical Biology Laboratory, National Cancer Institute, National Institutes of Health Frederick, Frederick, Maryland 21701, USA.
authors: Yuji
authors: Y
authors: Yamada
authors: Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors: Gerald
authors: G
authors: Brandacher
authors: Chemical Biology Laboratory, National Cancer Institute, National Institutes of Health Frederick, Frederick, Maryland 21701, USA.
authors: Joel P
authors: JP
authors: Schneider
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry / Q000494:pharmacology*; D008807:Mice, Inbred BALB C; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000187:drug effects / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate