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Biomaterials modulate interleukin-8 and other inflammatory proteins during reepithelialization in cutaneous partial-thickness wounds in pigs.

ABSTRACT: Acute and chronic cutaneous wounds remain a clinical challenge that require a mechanistic understanding to advance treatment options. For example, the role of inflammatory mediators during wound healing is not completely understood. Biomimetic materials, such as an in situ photopolymerizable semi-interpenetrating network (sIPN) derived from extracellular matrix components, show great potential in improving healing through the delivery of therapeutic agents and the function as a temporary tissue scaffold. In this study, we characterized the temporal profile of porcine cutaneous partial-thickness wound healing in response to Xeroform and sIPN treatment via histological and inflammatory protein analyses in epidermal, remodeling dermal, and dermal regions. Generally, interleukin (IL)-1?, IL-2, IL-4, IL-6, IL-10, IL-12p70, interferon-?, and tumor necrosis factor-?, but not IL-8, were expressed in the epidermis and remodeling dermis in a time course that followed the progression of epidermal maturation in response to both treatments. Differences in cellularity and protein expression were observed between treatments in a time- and region-dependent manner. In particular, the healing response to sIPN exemplified a potentially key relationship between IL-8 expression and reepithelialization. These results provide insights into the expression of inflammatory mediators and the time course of cutaneous healing and the capacity for biomaterials to further modulate this relationship.

SUBMITTER: Kleinbeck KR

PROVIDER: S-EPMC3279954 | biostudies-literature | 2010 Sep-Oct

REPOSITORIES: biostudies-literature

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Biomaterials modulate interleukin-8 and other inflammatory proteins during reepithelialization in cutaneous partial-thickness wounds in pigs.

Kleinbeck Kyle R KR Faucher Lee D LD Kao Weiyuan J WJ

Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 20100819 5

Acute and chronic cutaneous wounds remain a clinical challenge that require a mechanistic understanding to advance treatment options. For example, the role of inflammatory mediators during wound healing is not completely understood. Biomimetic materials, such as an in situ photopolymerizable semi-interpenetrating network (sIPN) derived from extracellular matrix components, show great potential in improving healing through the delivery of therapeutic agents and the function as a temporary tissue ...[more]

PMID: 20731797

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Project description:Healing of burn wounds is often associated with scar formation due to excessive inflammation and delayed wound closure. To date, no effective treatment is available to prevent the fibrotic process. The Renin Angiotensin System (RAS) was shown to be involved in fibrosis in various organs. Statins (e.g. Atorvastatin), Angiotensin receptor antagonists (e.g. Losartan) and the combination of these drugs are able to reduce the local RAS activation, and reduced fibrosis in other organs. We investigated whether inhibition of the RAS could improve healing of burn wounds by treatment with Atorvastatin, Losartan or the combination of both drugs. Therefore, full and partial thickness burn wounds were inflicted on both flanks of Yorkshire pigs. Oral administration of Atorvastatin, Losartan or the combination was started at post-burn day 1 and continued for 28 days. Full thickness wounds were excised and transplanted with an autologous meshed split-thickness skin graft at post-burn day 14. Partial thickness wounds received conservative treatment. Atorvastatin treatment resulted in enhanced graft take and wound closure of the full thickness wounds, faster resolution of neutrophils compared to all treatments and reduced alpha-smooth muscle actin positive cells compared to control treatment. Treatment with Losartan and to a lesser extent the combination therapy resulted in diminished graft take, increased wound contraction and poorer scar outcome. In contrast, Losartan treatment in partial thickness wounds decreased the alpha-smooth muscle actin+ fibroblasts and contraction. In conclusion, we showed differential effects of Losartan and Atorvastatin in full and partial thickness wounds. The extensive graft loss seen in Losartan treated wounds is most likely responsible for the poor clinical outcome of these full thickness burn wounds. Therefore, Losartan treatment should not be started before transplantation in order to prevent graft loss. Atorvastatin seems to accelerate the healing process in full thickness wounds possibly by dampening the pro-inflammatory response.

Dataset Information

Biomaterials modulate interleukin-8 and other inflammatory proteins during reepithelialization in cutaneous partial-thickness wounds in pigs.

Publications

Biomaterials modulate interleukin-8 and other inflammatory proteins during reepithelialization in cutaneous partial-thickness wounds in pigs.

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