Name: severe burn injury in a swine model for clinical dressing assessment
Uploaded: 2018-11-06T12:30:00
Description: Watch this Scientific Journal Video about Severe Burn Injury in a Swine Model for Clinical Dressing Assessment at JoVE.com

This study was supported by a grant from the Tri-Service General Hospital; National Defense Medical Center, Taiwan (TSGH-C107-042); Ministry of Science and Technology, Taiwan (MOST 106-2314-B-016 -014); and the National Defense Medical Center (MAB-106-055; MAB-106-010; MAB-107-064).

Procedures involving animal subjects have been approved by the Animal Care Committee at National Defense Medical Center, Taiwan (R.O.C). This study was conducted in the Laboratory Animal Center at the National Defense Medical Center. Swine weighing between 20 and 25 kg has been successfully instrumented using this protocol.
1. Adaptation of the Animals to Human Handling
<ol>
	<li>After arrival in the facility, house the animals solitarily but let them interact with each other.</li>
	<li>Prov...

<ol>
	<li>Sen, C. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+skin+wounds:+a+major+and+snowballing+threat+to+public+health+and+the+economy.">Human skin wounds: a major and snowballing threat to public health and the economy.</a> Wound Repair Regeneration. 17, 763-771 (2009).</li><li>Sen, C. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Wound+healing+essentials:+let+there+be+oxygen.">Wound healing essentials: let there be oxygen.</a> Wound Repair Regeneration. 17, 1-18 (2009).</li><li>Verhaegen, P. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differences+in+collagen+architecture+between+keloid,+hypertrophic+scar,+normotrophic+scar,+and+normal+skin:+an+objective+histopathological+analysis.">Differences in collagen architecture between keloid, hypertrophic scar, normotrophic scar, and normal skin: an objective histopathological analysis.</a> Wound Repair Regeneration. 17, 649-656 (2009).</li><li>Swindle, M. M., Adams, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Experimental Surgery and Physiology: Induced Animal Models of Human Disease. , (1988).</li><li>Swindle, M. M., Smith, A. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Swine as Models in Biomedical Research. , (1992).</li><li>Tumbleson, M. E., Schook, L. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Advances in Swine in Biomedical Research. Vols 1-2. , (1996).</li><li>Wang, C. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Enhanced+wound-healing+performance+of+a+phyto-polysaccharide-enriched+dressing+-+a+preclinical+small+and+large+animal+study.">Enhanced wound-healing performance of a phyto-polysaccharide-enriched dressing - a preclinical small and large animal study.</a> International Wound Journal. 14, 1359-1369 (2017).</li><li>Rowan, M. P., Cancio, L. C., Elster, E. A., Burmeister, D. M., Rose, L. F., Natesan, S., Chan, R. K., Christy, R. J., Chung, K. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Burn+wound+healing+and+treatment:+review+and+advancements.">Burn wound healing and treatment: review and advancements.</a> Journal of Critical Care. 19, 243 (2015).</li><li>Wong, V. W., Sorkin, M., Glotzbach, J. P., Longaker, M. T., Gurtner, G. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surgical+approaches+to+create+murine+models+of+human+wound+healing.">Surgical approaches to create murine models of human wound healing.</a> Journal of Biomedicine and Biotechnology. 969618, 8 (2011).</li><li>Gaines, C., Poranki, D., Du, W., Clark, R. A., Van Dyke, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+a+porcine+deep+partial+thickness+burn+model.">Development of a porcine deep partial thickness burn model.</a> Burns. 39, 311-319 (2013).</li><li>Gnyawali, S. C., Barki, K. G., Mathew-Steiner, S. S., Dixith, S., Vanzant, D., Kim, J., Dickerson, J. L., Datta, S., Powell, H., Roy, S., Bergdall, V., Sen, C. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High-resolution+harmonics+ultrasound+imaging+for+non-invasive+characterization+of+wound+healing+in+a+pre-clinical+swine+model.">High-resolution harmonics ultrasound imaging for non-invasive characterization of wound healing in a pre-clinical swine model.</a> PLoS One. 10 (3), e0122327 (2015).</li><li>Eaglstein, W. H., Mertz, P. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=New+methods+for+assessing+epidermal+wound+healing:+the+effects+of+triamcinolone+acetonide+and+polyethelene+film+occlusion.">New methods for assessing epidermal wound healing: the effects of triamcinolone acetonide and polyethelene film occlusion.</a> Journal of Investigative Dermatology. 71, 332-384 (1978).</li><li>Swindle, M. M., Smith, A. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparative+anatomy+and+physiology+of+the+pig.">Comparative anatomy and physiology of the pig.</a> Scandinavian Journal of Laboratory Animal Sciences. 25, 1-10 (1998).</li><li>Swindle, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Swine in the Laboratory: Surgery, Anesthesia, Imaging and Experimental Techniques. , (2007).</li><li>Mertz, P. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=IL-1+as+a+potent+inducer+of+wound+re-epithelization.">IL-1 as a potent inducer of wound re-epithelization.</a> Progress in Clinical and Biological Research. 365, 473-480 (1991).</li><li>Eming, S. A., Martin, P., Tomic-Canic, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Wound+repair+and+regeneration:+mechanisms,+signaling,+and+translation.">Wound repair and regeneration: mechanisms, signaling, and translation.</a> Science Translation Medicine. 6, 265-266 (2014).</li><li>Aryza, M. J., Baryza, G. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Vancouver+Scar+Scale:+an+administration+tool+and+its+interrater+reliability.">The Vancouver Scar Scale: an administration tool and its interrater reliability.</a> The Journal of Burn &amp; Rehabilitation. 16, 535-538 (1995).</li><li>Bystrom, A., Claesson, R., Sundqvist, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+antibacterial+effect+of+camphorated+paramonochlorophenol,+camphorated+phenol+and+calcium+hydroxide+in+the+treatment+of+infected+root+canals.">The antibacterial effect of camphorated paramonochlorophenol, camphorated phenol and calcium hydroxide in the treatment of infected root canals.</a> Endodontics &amp; Dental Traumatology. 1, 170-175 (1985).</li><li>Reig, A., Tejerina, C., Codina, J., Hidalgo, J., Mirabet, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Application+of+a+new+cicatrization+dressing+in+treating+second-degree+burns+and+donor+sites.">Application of a new cicatrization dressing in treating second-degree burns and donor sites.</a> Annals of Burn and Fire Disasters. 4, 174 (1991).</li><li>Hindy, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparative+study+between+sodium+carboxymethyl-cellulose+silver,+moist+exposed+burn+ointment,+and+saline-soaked+dressing+for+treatment+of+facial+burns.">Comparative study between sodium carboxymethyl-cellulose silver, moist exposed burn ointment, and saline-soaked dressing for treatment of facial burns.</a> Annals of Burn and Fire Disasters. 22, 131-137 (2009).</li><li>Galiano, R. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Topical+vascular+endothelial+growth+factor+accelerates+diabetic+wound+healing+through+increased+angiogenesis+and+by+mobilizing+and+recruiting+bone+marrow-derived+cells.">Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells.</a> The American Journal of Pathology. 164, 1935-1947 (2004).</li><li>Thangarajah, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+molecular+basis+for+impaired+hypoxia-induced+VEGF+expression+in+diabetic+tissues.">The molecular basis for impaired hypoxia-induced VEGF expression in diabetic tissues.</a> Proceedings of the National Academy of Sciences of the United States of America. , 13505-13510 (2009).</li></ol>

The present study established a swine model of severe burn injury and examined the model using a CAPS-containing dressing. Our results suggest that this swine model can be used for monitoring the clinical performance of experimental dressings, including antibacterial property. Wound healing rate, wound closure, and antibacterial activity were also analyzed using VSS, H&#38;E staining, and antibacterial test. The use of animal burn models has been developed as a valuable tool to review the pathophysiology of burn injury. ...

A burn injury initiates the inflammatory process and induces complex pathological effects, which influence numerous body functions immediately after an accident, resulting in negative impact on patients&#39; quality of life. Impaired wound healing causes significant morbidity and mortality among patients with diabetes mellitus1,2. Most patients with burn injuries experience pain during burn wound debridement, which is known as an excruciating process despite the use of powerful opioid analgesics3.
In contrast to other mammals, swine share several anatomic and physiologic characteristics with humans regarding the process of epithelialization, cellular proliferation, and angiogenesis. This makes swine a potentially better model for certain procedures and studies, and they are often used in subsequent studies that demonstrated promising results in mice. These features have led to the increasing use of swine as a major species in preclinical testing. Recently, a rapid increase in biomedical research with respect to cardiovascular, urinary, integumentary, and digestive systems has been observed4,5,6. This study aims to demonstrate a swine model of severe burn injury that eliminates wound contraction and provides a closer approximation of the human wound healing processes and the formation of new tissue. Six burn wounds were created symmetrically on the dorsum, three on each side of the spine of the swine. Next,anexperimental dressing was examined in a swine model of severe burn injury, which can be adapted to replicate human wound healing (Figure 1). The wounds were covered with a clinical dressing, which is composed of four layers: an inner contact layer of experimental materials, an inner intermediate layer of waterproof film, an outer intermediate layer of gauze, and an outer layer of adhesive plaster. A waterproof film keeps the wound environment moist while preventing bacterial infection and allowing gases to permeate the dressing. The outer intermediate layer of gauze was applied on the waterproof films and secured by an outer layer of adhesive plaster. At the completion of experiments, wound closure, wound area, and Vancouver Scar Scale (VSS) score were examined. The samples of skin resected from each animal post-sacrifice were histologically prepared and stained using hematoxylin and eosin (HE) staining. Antibacterial activity of each dressing in the context of wound healing was also examined in this model. Our previous study has demonstrated wound-healing performance in rat and swine model using a minimally invasive surgical technique7. Since there were six burn wounds on the dorsum within each swine, each experimental dressing was tested and evaluated in all positions to minimize bias related to wound healing process in different spots on the swine dorsum. Therefore, the swine model of severe burn injury established in this study provides a new approach for the evaluation of clinical dressings and facilitates the development of a novel treatment for burn injury. This study provides crucial tools to uncover the pathophysiology of burn wound healing.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr >
			<td>Sedation:</td>
			<td></td>
			<td></td>
			<td></td>	
	</tr>
		<tr >
			<td >Ketamine</td>
			<td >Merial</td>
			<td>2528 ESP</td>
			<td>10 mL vial</td>
			<td ></td>
		</tr>
		<tr >
			<td >Azaperone</td>
			<td >China chemical &#38; pharmaceutical</td>
			<td>47W406</td>
			<td>100 mL vial</td>
			<td ></td>
		</tr>
		<tr >
			<td >Atropine&#160;</td>
			<td >Oriental chemical works</td>
			<td>IN120802</td>
			<td>1 mL vial</td>
			<td ></td>
		</tr>
		<tr >
			<td>Anesthetic:</td>
			<td></td>
			<td></td>
			<td></td>	
	</tr>
		<tr >
			<td >Tiletamine+Zolazepam</td>
			<td >Virbac</td>
			<td>BC91</td>
			<td >5 mL vial</td>
			<td ></td>
		</tr>
		<tr >
			<td >Isoflurane</td>
			<td >Baxter</td>
			<td>N002A225</td>
			<td >100 mL vial</td>
			<td ></td>
		</tr>
		<tr >
			<td>Surgery:</td>
			<td></td>
			<td></td>
			<td></td>
			</tr>
		<tr >
			<td >Hair clippers</td>
			<td >Moser</td>
			<td>-</td>
			<td >-</td>
			<td ></td>
		</tr>
		<tr >
			<td >Povidone iodine scrub solution</td>
			<td >Ever star</td>
			<td>HA161202</td>
			<td >4 L barrel</td>
			<td ></td>
		</tr>
		<tr >
			<td >Modified iron</td>
			<td >-</td>
			<td>-</td>
			<td >-</td>
			<td ></td>
		</tr>
		<tr >
			<td >Electronic thermometer</td>
			<td >Dogger</td>
			<td>A9SA-ST9215C</td>
			<td >- 50~300&#8451;</td>
			<td ></td>
		</tr>
		<tr >
			<td >0.9% saline solution</td>
			<td >CHI SHENG</td>
			<td>KC130</td>
			<td >500 mL vial</td>
			<td ></td>
		</tr>
		<tr >
			<td >Gauze</td>
			<td >China Surgical Dressings Center</td>
			<td>MO15900080</td>
			<td >10 x10 cm</td>
			<td ></td>
		</tr>
		<tr >
			<td >CAPS</td>
			<td >CoreLeader Biotech Co., Ltd, Taipei, Taiwan</td>
			<td>-</td>
			<td >-</td>
			<td ></td>
		</tr>
		<tr >
			<td >Paper tape</td>
			<td >3M</td>
			<td>NDC-8333-1530-01</td>
			<td >2.5 cm x 9.1m</td>
			<td ></td>
		</tr>
		<tr >
			<td >Waterproof film</td>
			<td >3M</td>
			<td>NDC-8333-1600-40</td>
			<td >10 cm x 10 m</td>
			<td ></td>
		</tr>
		<tr >
			<td >Adhesive plaster</td>
			<td >Young chemical</td>
			<td>BH1426015</td>
			<td >10 cm x 10 m</td>
			<td ></td>
		</tr>
		<tr >
			<td>Dissection:</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr >
			<td >Pair of standard sharp/blunt straight scissors (14 cm)</td>
			<td >Shinetec instruments</td>
			<td>ST-S114</td>
			<td >-</td>
			<td ></td>
		</tr>
		<tr >
			<td >Halstead-Mosquito (12.5 cm)</td>
			<td >Shinetec instruments</td>
			<td>ST-H012</td>
			<td >-</td>
			<td ></td>
		</tr>
		<tr >
			<td >Handle(# 4)</td>
			<td >Shinetec instruments</td>
			<td>ST-H004</td>
			<td >-</td>
			<td ></td>
		</tr>
		<tr >
			<td >Surgical Blade(#21)</td>
			<td >Shinetec instruments</td>
			<td>ST-B021</td>
			<td >-</td>
			<td ></td>
		</tr>
		<tr >
			<td>Post-Fixation &#38; Storage:</td>
		</tr>
		<tr >
			<td >50 ml Plastic centrifuge tube&#160;</td>
			<td >Falcon</td>
			<td>352070</td>
			<td >-</td>
			<td ></td>
		</tr>
		<tr >
			<td >10% neutral buffered formalin</td>
			<td >Leica</td>
			<td>3800604EG</td>
			<td >-</td>
			<td ></td>
		</tr>
		<tr >
			<td>Bacterial Growth Experiments&#160;</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr >
			<td >Blood agar plate (BAP) (TSA with 5% sheep blood)&#160;</td>
			<td >CMP</td>
			<td>-</td>
			<td >90 mm Mono</td>
			<td></td>
		</tr>
	</tbody>
</table>

severe burn injury in a swine model for clinical dressing assessment

Wound healing is a dynamic repair process and is the most complex biological process in human life. In response to burn injury, alterations in biological pathways impair the inflammation response, resulting in delayed wound healing. Impaired wound healing frequently occurs in patients with diabetes leading to unfavorable outcomes such as amputation. Hence, dressings having beneficial effect in promoting burn wound repair are needed. However, studies on burn wound treatment are limited due to lack of proper animal models. Our previous study demonstrated wound-healing performance in rat and swine models using a minimally invasive surgical technique. This study aimed to demonstrate a swine model of severe burn injury that eliminates wound contraction and more closely approximates the human processes of re-epithelialization and new tissue formation. This protocol provides a detailed procedure for creating consistent burn wounds and examining the wound-healing performance under the treatment of an experimental dressing in a swine model. Six burn wounds were created symmetrically on the dorsum, which were covered with a clinical dressing composed of four layers: an inner contact layer of experimental materials, an inner intermediate layer of waterproof film, an outer intermediate layer of gauze, and an outer layer of adhesive plaster. Upon the completion of experiments, wound closure, wound area, and Vancouver Scar Scale score were examined. The samples of skin resected from each animal post-sacrifice were histologically prepared and stained using hematoxylin and eosin staining. Antibacterial activity of each dressing in the context of wound healing was also examined. The application of the clinical dressing to the wounds in swine model mimics the biological processes of human wound healing with respect to the processes of epithelialization, cellular proliferation, and angiogenesis. Therefore, this swine model provides an easy-to-learn, cost-effective, and robust method to assess the effect of clinical dressings in severe burn injury.

Burn duration of 30 seconds by hot iron resulted in wounds that were circular with a well-defined margin and uniformly pale with a rim of erythema (Figure 1D). Within each animal, there were six burn wounds on the dorsum. The arrangement of burn wounds was depicted in Figure 1K. Burn wounds were completely covered with CAPS-containing dressing and used to evaluate the depth of scar formation on post-burn days 0, 7, 21, and 42 and...

Watch this Scientific Journal Video about Severe Burn Injury in a Swine Model for Clinical Dressing Assessment at JoVE.com

Severe Burn Injury in a Swine Model for Clinical Dressing Assessment

To closely mimic the mode of burn injuries requires the interplay between clinical observation and studies in animal models. In this study, a swine model of severe burn injury was established to assess an experimental dressing in physiological and pathophysiological settings.

Wound healing is a dynamic repair process and is the most complex biological process in human life. In response to burn injury, alterations in biological ...

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