title: Release of insulin from PLGA-alginate dressing stimulates regenerative healing of burn wounds in rats.
abstract: 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/cm(2) 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.
authors: Department of Cell Biology and Neuroscience, University of California at Riverside, Riverside, CA, 92521, U.S.A.
authors: Sandeep
authors: S
authors: Dhall
authors: 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.
authors: João P
authors: JP
authors: Silva
authors: 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.
authors: Yan
authors: Y
authors: Liu
authors: Department of Chemical Engineering, Queen's University, Kingston, ON, Canada, K7L 3N6.
authors: Michael
authors: M
authors: Hrynyk
authors: Department of Cell Biology and Neuroscience, University of California at Riverside, Riverside, CA, 92521, U.S.A.
authors: Monika
authors: M
authors: Garcia
authors: Department of Cell Biology and Neuroscience, University of California at Riverside, Riverside, CA, 92521, U.S.A.
authors: Alex
authors: A
authors: Chan
authors: Department of Bioengineering, University of California at Riverside, Riverside, CA 92521, U.S.A.
authors: Julia
authors: J
authors: Lyubovitsky
authors: Department of Chemical Engineering, Queen's University, Kingston, ON, Canada, K7L 3N6.
authors: Ronald J
authors: RJ
authors: Neufeld
authors: Department of Cell Biology and Neuroscience, University of California at Riverside, Riverside, CA, 92521, U.S.A. manuela.martins@ucr.edu.
authors: Manuela
authors: M
authors: Martins-Green
mesh_terms: D000279:Administration, Cutaneous; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001458:Bandages; D002056:Burns / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002626:Chemistry, Pharmaceutical; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism; D061386:Insulin, Regular, Human / Q000008:administration & dosage* / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D020556:Neutrophil Infiltration / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012995:Solubility; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000464:Alginates; D016207:Cytokines; D004337:Drug Carriers; D018836:Inflammation Mediators; D061386:Insulin, Regular, Human; D017382:Reactive Oxygen Species; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen
keywords: angiogenesis; burn healing; collagen; insulin; macrophage; neutrophils; oxidative stress