Question

What is the best excision wound model in mice/rat for wound healing study?

Animal study is important step before the clinical trial of the study of wound healing. During the animal study we may have a few problem to choose the excision wound model in mice/ rat.

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  • Dayanjan Wijesinghe · Virginia Commonwealth University
    Wow. This is a topic that a book can be written on. The model that we use in our lab are mice with two full thickness excision wounds on the shaved and depilated dorsom on either side of the spine. The two wounds allow us to compare treatments with their contralateral controls. We often use stents to minimize the healing by contraction and force more healing via epithelialization in order to better simulate the wounds in humans. Other excissional wound models include the mouse ear and tail models where healing is mainly via epithelialization and not contraction. Even with all precautions taken the similarity of healing between mouse/rat and humans are slightly better than 50%. What type of experiment are you trying to set up?
  • Tobias Hirsch · Ruhr-Universität Bochum
    i totally agree with Dayanjan Wijesinghe. Therefore we mainly use preclinical large animal wound healing models in pigs, which is much better comparable to the wound healing situation in humans
  • Dimitrios Karypidis · Cardiff University
    This is indeed a question that diserves an extended answer. However instead of discussing each one of the available options I could vote for what I have used repeatedly with excellent results. The excision involves variable thickness of tissue ( skin without the panniculus, skin with vascularized panniculus,skin and fascia, skin fascia and dorsal muscle compartment) in the interscapular region. Usually it is elliptical with a small radius of 1cm and a big radius of 2 cm in a rat about 300 g. Much smaller interscapular defects can be utilized in smaller animals e.g. mice. The main advantage is that the animal cannot reach the wound region when grooming or because of the irritation. It is also very easily monitored and handled in matters of wound dressing changes, tie over cleaning etc
  • Dayanjan Wijesinghe · Virginia Commonwealth University
    Couldn't agree with you more Tobias. This is the model of choice for most of us although the cost per experiment is high. The correlation to human healing is much better than rats and mice although still not a perfect match.
  • Alfredo Gragnani · Universidade Federal de São Paulo
    Depends on your main question, and how long do you plan to study, but in mice prefer squared configuration with 4 x 4 cms in back. Round configuration or less than 2x2 cms close too soon. Do not forget to take off the panniculus carnosus.
  • Harriet Hopf · University of Utah
    I would also advocate looking for human volunteer models (Bob Diegelmann at Virginia Commonwealth is an expert). The concordance between results in animals and those in human trials is depressingly poor (see, for example, growth factors for wound healing). So be very careful in using animal models and in extrapolating to humans. Animal models are probably a little better for acute wound healing, but animal models of chronic wounds (and particularly of the usual human etiologies for chronic wounds-- because 'chronic wound' is not a diagnosis) are a huge challenge.
  • Ahmad Hata Rasit · University Malaysia Sarawak
    Based on my observation, afew factor can lead to a few problem. some of the proble already addres by Dimitrios are good suggestion. The used of Rat/mice cage and assesory may contribute to the wound care of the rat/mice. naapropriate small accesory i the cage may contribute to fixation of graft over the wound. Question: Do we need to standardize the animal cage for specific animal modl study, hope you all can give your opinion. Thank you
  • Laura Bolton · Robert Wood Johnson University Hospital
    Guinea pig full-thickness excision is most similar to humans because guinea pigs grow hair in same mosaic pattern as humans so there are fewer hair-growth artifacts than for rats, mice, rabbits that grow hair in waves. Use circular wounds made by pinching a fold of skin then cutting to a standardized size with sharp/sharp scissors to avoid corner artifacts or crushing damage at the wound edges (e.g. see attached: Bolton, L.L., Oleniacz, W., Constantine, B., Kelliher, B.O., Jensen, D., Means, B., Rovee, D. Repair and antibacterial effects of topical antiseptic agents. In H. Maibach & N. Lowe (Eds) Models in Dermatology, Vol. 2, Karger, Basel, 1985, pp.145-158.)
    7 Bolton, L.L., Constantine, B. Partial-thickness wound models in small animals. In H. Maibach and N. Lowe (Eds) Models in Dermatology, Vol. 3, Karger, Basel, 1986, pp.190-195.
    8 Bolton, L.L., Pines, E, Rovee, D.T. Wound Healing and Integumentary System. Experimental Surgery and Physiology: Induced Animals Models of Human Disease, Swindle, M. Michael/Adams, Roberg, J. 1988:1-9.
    .Also, guinea pig digestive metabolism is more like humans than that of mice or rats who synthesize their own Vitamin C.

    If you wish to do work that translates to human clinical use, it is a good idea to avoid stents or other artificial techniques that do not resemble causes for human delayed healing.

    A good model for delayed healing is the diabetic mouse full-thickness excision used in research, e.g. by Rogers et al. (Rodgers KE, Roda N, Felix JC, Espinoza T, Maldonado S, diZerega G. Histological evaluation of the effects of angiotensin peptides on wound repair in diabetic mice. Experimental Dermatology 2003; 12(6):784-790.)

    Learn more about pros and cons and best use of each model in these sources:
    1 Bolton, L.L., Constantine, B. Partial-thickness wound models in small animals. In H. Maibach and N. Lowe (Eds) Models in Dermatology, Vol. 3, Karger, Basel, 1986, pp.190-195.
    2 Bolton, L.L., Pines, E, Rovee, D.T. Wound Healing and Integumentary System. Experimental Surgery and Physiology: Induced Animals Models of Human Disease, Swindle, M. Michael/Adams, Roberg, J. 1988:1-9.
  • Human clinical models are best. There may be ethical issues. The next best model is the pig. However, it is too expensive. Rats/Mice have different degree of wound contracture & epithelialisation rate compared to human. There is no abnormal wound healing in rats/mice (eg. keloids etc.). Post excision/surgical specimens during wound debridement in humans may help. The best way to go about is to carefully consider all factors, as well as the cost & design your experiment accordingly.

    Cheers! & all the best!

    Dr. William Mol (MBBS, PhD)
    Plastic surgeon, Papua New Guinea
  • Amy Dugan · Sinclair Community College
    Well in my work I focus on burn injury. I perform a 3rd degree flame burn injury that is ~ 15% of the total body surface area. A literature search of skin wound healing models in mice did not come up with many new publications. I see this is still commonly referred to http://onlinelibrary.wiley.com/doi/10.1111/j.1067-1927.2004.12404.x/full
  • Dimitrios Karypidis · Cardiff University
    Animal cages are usually standardized in terms of providing sufficient space, enabling easy food and water access, not obstracting light, not allowing the animal to self-inflict injuries or trauma by adjusting the space between cage bars so that no animal part fits in or no part of the cage is chewable etc. Some important aspects include the height of the cage which should be high enough so that the dorsal dressings can't get stuck or ripped off by the cage roof. The automatic water supply pipes have to be adjusted so that they don't protrude more than a few cm inside the cage. The floor of the cage should be well covered by wood chips or any other approved absorbent non toxic inedible insulating material. It is also important that animals that have undergone surgery should be kept one in each cage to avoid interaction or attempts of the other animal to chew on the dressings. It is also easier to handle one animal per cage when you have to administer any agents postoperatively. Generally speaking when the research methodology of a study incudes modifications, analysis, investigation of any parameter that is related to the animals' housing enviroment and conditions, it is imperative to use validated and standardized housing protocols ( e.g. when immunosuppresants are to be used or special nutritional modifications are examined or when perinatal conditions are involved etc). There is no general wound healing animal housing protocolapart from the basic-standard one that I mentioned previously. Other than that, every study has its own specific requirements based on previously used and approved protocols. I hope I've helped. Perhaps if you could share the exact research methodology with me I could come up with more specific suggestions.
  • Amy Dugan · Sinclair Community College
    How ironic the timing of this article out Sept 27 in Nature. Mice Grow New Skin, with No Scars http://www.ncbi.nlm.nih.gov/pubmed/23018966

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