Abstract
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/PAA) bilayers deposited, providing burst release of up to 0.98 ± 0.06 μg/cm2 of CX over 24 h, followed by zero-order release of 0.35 ± 0.04 μg/cm2/day for another week. Although the CX concentrations released were below the reported in vitro cytotoxicity limit (5 μg/mL over 24 h) for human dermal fibroblasts, they killed 4 log10 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 ∼105 CFU/cm2 of S. aureus and treated with CX-functionalized Biobrane demonstrated a 3 log10 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 6783-6792 |
| Number of pages | 10 |
| Journal | Biomaterials |
| Volume | 33 |
| Issue number | 28 |
| DOIs | |
| State | Published - Oct 2012 |
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Keywords
- Antimicrobial
- Chlorhexidine
- Dressing
- Mice
- Polyelectrolye multilayers
- Wound
ASJC Scopus subject areas
- Biomaterials
- Bioengineering
- Ceramics and Composites
- Mechanics of Materials
- Biophysics
Cite this
Polymeric multilayers that localize the release of chlorhexidine from biologic wound dressings. / Agarwal, Ankit; Nelson, Tyler B.; Kierski, Patricia R.; Schurr, Michael J.; Murphy, Christopher J; Czuprynski, Charles J.; McAnulty, Jonathan F.; Abbott, Nicholas L.
In: Biomaterials, Vol. 33, No. 28, 10.2012, p. 6783-6792.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Polymeric multilayers that localize the release of chlorhexidine from biologic wound dressings
AU - Agarwal, Ankit
AU - Nelson, Tyler B.
AU - Kierski, Patricia R.
AU - Schurr, Michael J.
AU - Murphy, Christopher J
AU - Czuprynski, Charles J.
AU - McAnulty, Jonathan F.
AU - Abbott, Nicholas L.
PY - 2012/10
Y1 - 2012/10
N2 - 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/PAA) bilayers deposited, providing burst release of up to 0.98 ± 0.06 μg/cm2 of CX over 24 h, followed by zero-order release of 0.35 ± 0.04 μg/cm2/day for another week. Although the CX concentrations released were below the reported in vitro cytotoxicity limit (5 μg/mL over 24 h) for human dermal fibroblasts, they killed 4 log10 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 ∼105 CFU/cm2 of S. aureus and treated with CX-functionalized Biobrane demonstrated a 3 log10 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.
AB - 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/PAA) bilayers deposited, providing burst release of up to 0.98 ± 0.06 μg/cm2 of CX over 24 h, followed by zero-order release of 0.35 ± 0.04 μg/cm2/day for another week. Although the CX concentrations released were below the reported in vitro cytotoxicity limit (5 μg/mL over 24 h) for human dermal fibroblasts, they killed 4 log10 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 ∼105 CFU/cm2 of S. aureus and treated with CX-functionalized Biobrane demonstrated a 3 log10 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.
KW - Antimicrobial
KW - Chlorhexidine
KW - Dressing
KW - Mice
KW - Polyelectrolye multilayers
KW - Wound
UR - http://www.scopus.com/inward/record.url?scp=84864004831&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864004831&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2012.05.068
DO - 10.1016/j.biomaterials.2012.05.068
M3 - Article
C2 - 22784602
AN - SCOPUS:84864004831
VL - 33
SP - 6783
EP - 6792
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
IS - 28
ER -