Burn wound healing involves a complex set of overlapping processes in an environment conducive to ischaemia, inflammation and infection costing $7.5 billion/year in the U.S.A. alone, in addition to the morbidity and mortality that occur when the burns are extensive. We previously showed that insulin, when topically applied to skin excision wounds, accelerates re-epithelialization and stimulates angiogenesis. More recently, we developed an alginate sponge dressing (ASD) containing insulin encapsulated in PLGA [poly(D,L-lactic-co-glycolic acid)] microparticles that provides a sustained release of bioactive insulin for >20 days in a moist and protective environment. We hypothesized that insulin-containing ASD accelerates burn healing and stimulates a more regenerative, less scarring healing. Using heat-induced burn injury in rats, we show that burns treated with dressings containing 0.04 mg insulin/cm2 every 3 days for 9 days have faster closure, a higher rate of disintegration of dead tissue and decreased oxidative stress. In addition, in insulin-treated wounds, the pattern of neutrophil inflammatory response suggests faster clearing of the burned dead tissue. We also observe faster resolution of the pro-inflammatory macrophages. We also found that insulin stimulates collagen deposition and maturation with the fibres organized more like a basket weave (normal skin) than aligned and cross-linked (scar tissue). In summary, application of ASD-containing insulin-loaded PLGA particles on burns every 3 days stimulates faster and more regenerative healing. These results suggest insulin as a potential therapeutic agent in burn healing and, because of its long history of safe use in humans, insulin could become one of the treatments of choice when repair and regeneration are critical for proper tissue function.
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Research Article|
October 22 2015
Release of insulin from PLGA–alginate dressing stimulates regenerative healing of burn wounds in rats
Sandeep Dhall;
Sandeep Dhall
*Department of Cell Biology and Neuroscience, University of California at Riverside, Riverside, CA, 92521, U.S.A.
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João P. Silva;
João P. Silva
*Department of Cell Biology and Neuroscience, University of California at Riverside, Riverside, CA, 92521, U.S.A.
†Centre for Biological Engineering, University of Minho, Campus Gualtar, Braga 4710-057, Portugal
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Yan Liu;
Yan Liu
*Department of Cell Biology and Neuroscience, University of California at Riverside, Riverside, CA, 92521, U.S.A.
‡Department of Burn and Plastic Surgery, Rujin Hospital, Shanghai 200025, China
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Michael Hrynyk;
Michael Hrynyk
§Department of Chemical Engineering, Queen's University, Kingston, ON, Canada, K7L 3N6
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Monika Garcia;
Monika Garcia
*Department of Cell Biology and Neuroscience, University of California at Riverside, Riverside, CA, 92521, U.S.A.
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Alex Chan;
Alex Chan
*Department of Cell Biology and Neuroscience, University of California at Riverside, Riverside, CA, 92521, U.S.A.
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Julia Lyubovitsky;
Julia Lyubovitsky
║Department of Bioengineering, University of California at Riverside, Riverside, CA 92521, U.S.A.
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Ronald J. Neufeld;
Ronald J. Neufeld
§Department of Chemical Engineering, Queen's University, Kingston, ON, Canada, K7L 3N6
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Manuela Martins-Green
*Department of Cell Biology and Neuroscience, University of California at Riverside, Riverside, CA, 92521, U.S.A.
Correspondence: Professor Manuela Martins-Green (email manuela.martins@ucr.edu).
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Publisher: Portland Press Ltd
Received:
June 08 2015
Revision Received:
August 03 2015
Accepted:
August 26 2015
Accepted Manuscript online:
August 26 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2015 Authors; published by Portland Press Limited
2015
Clin Sci (Lond) (2015) 129 (12): 1115–1129.
Article history
Received:
June 08 2015
Revision Received:
August 03 2015
Accepted:
August 26 2015
Accepted Manuscript online:
August 26 2015
Citation
Sandeep Dhall, João P. Silva, Yan Liu, Michael Hrynyk, Monika Garcia, Alex Chan, Julia Lyubovitsky, Ronald J. Neufeld, Manuela Martins-Green; Release of insulin from PLGA–alginate dressing stimulates regenerative healing of burn wounds in rats. Clin Sci (Lond) 1 December 2015; 129 (12): 1115–1129. doi: https://doi.org/10.1042/CS20150393
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