Animal models of wound repair: Are they cutting it?

Ansell, David M.; Holden, Kirsty; Hardman, Matthew J.

doi:10.1111/j.1600-0625.2012.01540.x

Cited by 118 publications

(100 citation statements)

References 88 publications

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“…We identify delays to multiple aspects of the healing process, suggesting LPS administration provides a simple, reproducible model of bacterially delayed healing in mice. As with other current delayed healing murine models, 43 we suggest that our LPS model provides a clinically relevant means to dissect the host response to microorganisms in wound infection, with relevance to human chronic wounds. To test the suitability of this model, we co-treated with 17β-estradiol, the major oestrogen naturally occurring in mammals.…”

mentioning

confidence: 99%

Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair

Crompton

Williams

Ansell

et al. 2016

Laboratory Investigation

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Wound infection is a major clinical problem, yet understanding of bacterial host interactions in the skin remains limited. Microbe-derived molecules, known as pathogen-associated molecular patterns, are recognised in barrier tissues by pattern-recognition receptors. In particular, the pathogen-associated molecular pattern, lipopolysaccharide (LPS), a component of microbial cell walls and a specific ligand for Toll-like receptor 4, has been widely used to mimic systemic and local infection across a range of tissues. Here we administered LPS derived from Klebsiella pneumoniae, a species of bacteria that is emerging as a wound-associated pathogen, to full-thickness cutaneous wounds in C57/BL6 mice. Early in healing, LPS-treated wounds displayed increased local apoptosis and reduced proliferation. Subsequent healing progression was delayed with reduced re-epithelialisation, increased proliferation, a heightened inflammatory response and perturbed wound matrix deposition. Our group and others have previously demonstrated the beneficial effects of 17β-estradiol treatment across a range of preclinical wound models. Here we asked whether oestrogen would effectively promote healing in our LPS bacterial infection model. Intriguingly, co-treatment with 17β-estradiol was able to promote re-epithelialisation, dampen inflammation and induce collagen deposition in our LPS-delayed healing model. Collectively, these studies validate K. pneumoniae-derived LPS treatment as a simple yet effective model of bacterial wound infection, while providing the first indication that oestrogen could promote cutaneous healing in the presence of infection, further strengthening the case for its therapeutic use.

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confidence: 99%

Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair

Crompton

Williams

Ansell

et al. 2016

Laboratory Investigation

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“…It is also possible secondary to the improved angiogenesis or granulation tissue formation. In conclusion, our study suggests unique therapeutic value of TOE in wounds especially for poorly perfused chronic wounds that often lack an adequate oxygen supply (27).…”

Section: Discussionmentioning

confidence: 99%

Effects of a topical aqueous oxygen emulsion on collagen deposition and angiogenesis in a porcine deep partial‐thickness wound model

Ollague

Zhu

et al. 2013

Experimental Dermatology

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Additional Supporting Information may be found in the online version of this article: Figure S1. Inhibition of E6 and E7 expressions by inducible shRNA technique alters p53 and pRb protein levels. Figure S2. Characterization of the effects of viral E6 and E7 gene inhibition on cell proliferation.Data S1. Materials and methods. Abstract: A porcine deep partial-thickness wound model was used to evaluate the effects of a newly developed topical aqueous oxygen emulsion (TOE) on wound repair. The wounds were treated with TOE, which contains super-saturated oxygen or vehicle control. Semiquantitative immunofluorescent staining was performed to examine protein production for type I and type III collagen and vascular endothelial growth factor (VEGF). Immunofluorescent staining revealed higher protein levels of type I and type III collagen and VEGF in the TOE treatment group. Histological analysis also revealed improved angiogenesis and granulation tissue formation with topical TOE treatment and was consistent with the protein expression. In addition, the histology examination demonstrated faster epithelialization in wounds treated with TOE. The study suggests that sustained high levels of oxygen released by TOE may promote the process of wound repair through increasing collagen deposition and angiogenesis as well as stimulating epithelialization.

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“…Therefore, diabetes, along with aging or obesity, is only one factor that alters and prolongs the healing process. It has been reported that STZ-treated rats do not necessarily suffer a healing delay as seen in chronic wounds (Davidson 1998;LeGrand 1998;Michaels, et al 2007, Ansell, et al 2012). This may explain why the differences between the treated and control groups diminished as the study proceeded.…”

Section: Discussionmentioning

confidence: 99%

rhEGF-loaded PLGA-Alginate microspheres enhance the healing of full-thickness excisional wounds in diabetised Wistar rats

Gainza

Aguirre

Pedraz

et al. 2013

European Journal of Pharmaceutical Sciences

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Diabetic foot ulcers (DFUs) represent a major clinical challenge in the ageing population. To address this problem, rhEGF-loaded Poly-Lactic-co-Glycolic-Acid (PLGA)-Alginate microspheres (MS) were prepared by a modified w/o/w-doubleemulsion/solvent evaporation method. Different formulations were evaluated with the aim of optimising MSs properties by adding NaCl to the surfactant solution and/or the solvent removal phase and adding alginate as a second polymer. The characterization of the developed MS showed that alginate incorporation increased the encapsulation efficiency (EE) and NaCl besides increasing the EE also became the particle surface smooth and regular. Once the MS were optimised, the target loading of rhEGF was increased to 1% (PLGA-Alginate MS), and particles were sterilised by gamma radiation to provide the correct dosage for in vivo studies. In vitro cell culture assays demonstrated that neither the microencapsulation nor the sterilisation process affected rhEGF bioactivity or rhEGF wound contraction. Finally, the MS were evaluated in vivo for treatment of the full-thickness wound model in diabetised Wistar rats. rhEGF MS treated animals showed a statistically significant decrease of the wound area by days 7 and 11, a complete re-epithelisation by day 11 and an earlier resolution of the inflammatory process. Overall, these findings demonstrate the promising potential of rhEGF-loaded MS (PLGA-Alginate MS) to promote faster and more effective wound healing, and suggest its possible application in DFU treatment.

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Animal models of wound repair: Are they cutting it?

Cited by 118 publications

References 88 publications

Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair

Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair

Effects of a topical aqueous oxygen emulsion on collagen deposition and angiogenesis in a porcine deep partial‐thickness wound model

rhEGF-loaded PLGA-Alginate microspheres enhance the healing of full-thickness excisional wounds in diabetised Wistar rats

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