Polymeric multilayers that localize the release of chlorhexidine from biologic wound dressings

被引:82
作者
Agarwal, Ankit [1 ]
Nelson, Tyler B. [1 ]
Kierski, Patricia R. [2 ]
Schurr, Michael J. [3 ]
Murphy, Christopher J. [4 ]
Czuprynski, Charles J. [5 ]
McAnulty, Jonathan F. [2 ]
Abbott, Nicholas L. [1 ]
机构
[1] Univ Wisconsin Madison, Dept Chem & Biol Engn, Madison, WI USA
[2] Univ Wisconsin Madison, Sch Vet Med, Dept Surg Sci, Madison, WI USA
[3] Univ Colorado Denver, Sch Med, Dept Surg, Denver, CO USA
[4] Univ Calif Davis, Sch Vet Med, Dept Surg & Radiol Sci, Davis, CA USA
[5] Univ Wisconsin Madison, Sch Vet Med, Dept Pathobiol Sci, Madison, WI USA
关键词
Polyelectrolye multilayers; Chlorhexidine; Wound; Dressing; Mice; Antimicrobial; POLYELECTROLYTE MULTILAYERS; STAPHYLOCOCCUS-AUREUS; IN-VITRO; BIOBRANE; FILMS; BURN; DIGLUCONATE; INHIBITION; INTERFACES; DIACETATE;
D O I
10.1016/j.biomaterials.2012.05.068
中图分类号
R318 [生物医学工程];
学科分类号
100103 [病原生物学];
摘要
Biologic wound dressings contain animal-derived components and are susceptible to high infection rates. To address this issue, we report an approach that permits incorporation of non-toxic levels of the small molecule antiseptic 'chlorhexidine' into biologic dressings. The approach relies on the fabrication of polyelectrolyte multilayer (PEMs) films containing poly(allylaminehydrochloride) (PAH), poly(-acrylicacid) (PAA), and chlorhexidine acetate (CX) on elastomeric poly(dimethylsiloxane) (PDMS) sheets. The PEMs (20-100 nm thick) are subsequently stamped onto the wound-contact surface of a synthetic biologic dressing, Biobrane, which contains collagen peptides. Chlorhexidine loading in the PEMs was tailored by tuning the number of (CX/PM) bilayers deposited, providing burst release of up to 0.98 +/- 0.06 mu g/cm(2) of CX over 24 h, followed by zero-order release of 0.35 +/- 0.04 mu g/cm(2)/day for another week. Although the CX concentrations released were below the reported in vitro cytotoxicity limit (5 mu g/mL over 24 h) for human dermal fibroblasts, they killed 4 logo counts of pathogenic bacteria Staphylococcus aureus in solution. The CX/PEMs could be stamped onto Biobrane with high efficiency to provide CX release kinetics and in vitro antibacterial activity similar to that on PDMS stamps. In a full-thickness 'splinted' dermal wound-model in normal wild-type mice, the CX-functionalized Biobrane showed no decrease in either its adherence to the wound-bed or wound closure rate over 14 days. The murine wounds topically inoculated with similar to 105 CFU/cm(2) of S. aureus and treated with CX-functionalized Biobrane demonstrated a 3 log(10) decrease in the wound's bacterial burden within 3 days, compared to persistent bacterial colonization found in wounds treated with unmodified Biobrane (n = 10 mice, p < 0.005). Overall, this study presents a promising approach to prevent bacterial colonization in wounds under biologic dressings. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码:6783 / 6792
页数:10
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