The hairless mouse ear: an in vivo model for studying wound neovascularization

Barker, John H.; Kjølseth, Dorthe; Kim, Michael; Frank, Johannes; Bondàr, Imré; Uhl, Eberhard; Kamler, Markus; Meßmer, K.; Tobin, Gordon R.; Weiner, Leonard J.

doi:10.1046/j.1524-475x.1994.20208.x

Cited by 33 publications

(34 citation statements)

References 3 publications

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“…Our aim was to investigate the effects of a novel polihexanide-preserved wound covering gel on wound healing and skin microcirculation in a standardized mouse model [8] . The wound model in hairless mice allows for qualitative and quantitative analysis of the wound microcirculation after topical application of different formulations containing different ingredients [9] .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a Novel Polihexanide-Preserved Wound Covering Gel on Dermal Wound Healing

Goertz

Ring²,

Knie³

et al. 2009

Eur Surg Res

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Objective: Daily wound assessment, including dressing changes and the removal of old ointments causes discomfort for the patient. We therefore developed a new thermoreversible and transparent gel formulation that allows for filling wounds of different shapes and depths. The aim of the study was to investigate the effect of a wound covering gel on wound healing and the skin’s microcirculation. Materials and Methods: Investigations were carried out in a standardized and reproducible wound model (hairless mice SKH1/hr, n = 30). Three groups were studied by intravital fluorescence microscopy: treatment with polihexanide-preserved wound covering gel, a formulation containing 3% povidone (PVP)-iodine, and physiological saline for control. Microcirculatory standard parameters were analysed. Results: The non-perfused area vanished within 14 days due to angiogenesis. The venular diameter, oedema formation and functional capillary density showed no significant differences between the three groups. Conclusion: The use of the newly developed wound covering gel has no toxic effects on microcirculation and angiogenesis and reveals no significant differences in the overall assessment of microcirculation compared to the control group and the well-established PVP-iodine. The transparent antibacterial wound covering gel allows for direct wound assessment. Due to its thermoreversible gel formulation it enables good wound contact and easy handling.

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Section: Discussionmentioning

confidence: 99%

Evaluation of a Novel Polihexanide-Preserved Wound Covering Gel on Dermal Wound Healing

Goertz

Ring²,

Knie³

et al. 2009

Eur Surg Res

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“…The mouse ear is ∼300 μm thick, and the planar microvasculature can be clearly visualized in the absence of fur; thus, this model has been used in a number of wound healing studies. 27,28 The mice were anesthetized with an intraperitoneal injection of 0.15 ml of a stock solution containing a mixture of ketamine (50 mg/kg) and xylazine (5 mg/kg). The right ear of each mouse was injured by creating a 2-mm-diam, full-thickness excision wound using a biopsy punch.…”

Section: In Vivo Imaging Of Mouse Ear Vasculaturementioning

confidence: 99%

Multiexposure laser speckle contrast imaging of the angiogenic microenvironment

et al. 2011

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Abstract.We report the novel use of laser speckle contrast imaging (LSCI) at multiple exposure times (meLSCI) for enhanced in vivo imaging of the microvascular changes that accompany angiogenesis. LSCI is an optical imaging technique that can monitor blood vessels and the flow therein at a high spatial resolution without requiring the administration of an exogenous contrast agent. LSCI images are obtained under red (632 nm) laser illumination at seven exposure times (1-7 ms) and combined using a curve-fitting approach to obtain high-resolution meLSCI images of the rat brain vasculature. To evaluate enhancement in in vivo imaging performance, meLSCI images are statistically compared to individual LSCI images obtained at a single exposure time. We find that meLSCI reduced the observed variability in the LSCI-based blood-flow estimates by 30% and improved the contrast-to-noise ratio in regions with high microvessel density by 41%. The ability to better distinguish microvessels, makes meLSCI uniquely suited to longitudinal imaging of changes in the vascular microenvironment induced by pathological angiogenesis. We demonstrate this utility of meLSCI by sequentially monitoring, over days, the microvascular changes that accompany wound healing in a mouse ear model. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

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“…The ear of the homozygous hairless mouse measures about 13 mm 2 . The total thickness is approximately 300 µm with a central cartilage layer between two layers of skin [3,4,9,11,18,19]. All handling of the animals was performed under anesthesia (ketamine 50 mg/kg and xylazine hydrochloride 5 mg/kg i.p.).…”

Section: Animal Modelmentioning

confidence: 99%

“…Standardized, circular wounds (2.25 mm in diameter, 0.125 mm in depth) were created on the dorsal aspect of the ears, positioned between the anterior and middle principal neurovascular bundles. An incision was made using a circular punch-type knife, and a full-thickness layer of skin was removed with microsurgical technique, leaving the pineal cartilage layer intact [4].…”

Section: Wound Creationmentioning

confidence: 99%

In Vivo Effect of Tumor Necrosis Factor Alpha on Wound Angiogenesis and Epithelialization

Frank

Born²,

Barker

et al. 2003

European Journal of Trauma

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Background: The role of tumor necrosis factor alpha (TNF-␣) in wound healing is unclear and the results are contradictory. In vivo, TNF-␣ induces vessel growth, an important step in promoting wound healing. However, a reduced amount of collagen, hydroxyproline, and granulation tissue was found after TNF-␣ treatment. It is also unknown if this is a direct effect, by influencing cells involved in wound healing, or an indirect effect due to a negative or positive effect on cells such as macrophages. Material and Methods: The current study was undertaken to test the effect of TNF-␣ on wound epithelialization and neovascularization in vivo. In the first experiment, standardized full-thickness dermal wounds (2.25 mm diameter, 0.125 mm depth) were created on the dorsum of the ears of male hairless mice. The wounds were treated either with TNF-␣ (100 ng/ml, 1 µg/ml, 5 µg/ml; n = 10 per group), monoclonal TNF-␣ antibody (10 µg/ml; n = 10), or vehicle (n = 10). Wound epithelialization and neovascularization were analyzed every 3rd day by intravital microscopy until complete healing. In a second experiment, the same wound model was used, but in order to impair the healing process, macrophages were depleted. To reduce macrophages, two out of four groups (n = 10 per group) were pretreated with iota-carrageenan (MR groups), and the other two groups received only saline (N groups). One N group and one MR group were treated with TNF-␣ (1 µg/ml). The other N group and MR group received vehicle only (carboxymethylcellulose). Using intravital microscopy and computerized planimetry, wound epithelialization and neovascularization were measured every 3rd day until complete healing. Immunohistochemistry was performed to detect TNF-␣, macrophages, fibronectin, and vitronectin receptors. Results: In the first experiment the wounds treated with 1 µg/ml healed significantly earlier than controls (13.9 ± 2 vs. 17.3 ± 2.8 days, respectively; p < 0.05). Epithelialization in the antibody group was significantly slower compared to controls (20.1 ± 2 days; p < 0.05). Neovascularization was significantly enhanced in the group treated with 1 µg/ml TNF-␣ (p < 0.05). In the second experiment the wounds treated with TNF-␣ were significantly earlier epithelialized (13.1 ± 0.6) and vascularized (16.0 ± 0.5) compared to controls (16.8 ± 0.4 vs. 17.6 ± 0.5; p < 0.05). Wound closure was significantly delayed in the MR group treated with vehicle only (20.4 ± 1) and equal to controls in the MR group treated with TNF-␣ (16.8 ± 0.6). Conclusion:The results demonstrate the TNF-␣ accelerates wound epithelialization and neovascularization in this in vivo model. TNF-␣ is able to compensate for the negative effect of macrophage reduction and seems to have a direct effect on the wound-healing process.

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The hairless mouse ear: an in vivo model for studying wound neovascularization

Cited by 33 publications

References 3 publications

Evaluation of a Novel Polihexanide-Preserved Wound Covering Gel on Dermal Wound Healing

Evaluation of a Novel Polihexanide-Preserved Wound Covering Gel on Dermal Wound Healing

Multiexposure laser speckle contrast imaging of the angiogenic microenvironment

In Vivo Effect of Tumor Necrosis Factor Alpha on Wound Angiogenesis and Epithelialization

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