Release of insulin from PLGA-alginate dressing stimulates regenerative healing of burn wounds in rats
Autor: | Manuela Martins-Green, Sandeep Dhall, Ronald J. Neufeld, Monika Garcia, João Pedro Silva, Alex Chan, Julia G. Lyubovitsky, Yan Liu, Michael Hrynyk |
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Přispěvatelé: | Universidade do Minho |
Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
collagen
Burn injury Time Factors Angiogenesis medicine.medical_treatment Chemistry Pharmaceutical Pharmacology Medical and Health Sciences Rats Sprague-Dawley chemistry.chemical_compound angiogenesis Alginate dressing Polylactic Acid-Polyglycolic Acid Copolymer neutrophils Insulin Regular Human oxidative stress Regular Skin Drug Carriers General Medicine 3. Good health PLGA Chemistry Neutrophil Infiltration burn healing Administration Cytokines Female medicine.symptom Inflammation Mediators Burns Human medicine.medical_specialty insulin Alginates Neovascularization Physiologic Inflammation macrophage Administration Cutaneous Cicatrix medicine Animals Humans Lactic Acid Physiologic Neovascularization Wound Healing Science & Technology business.industry Animal Regeneration (biology) Insulin Bandages Surgery Rats Disease Models Animal Cutaneous chemistry Cardiovascular System & Hematology Solubility Disease Models Pharmaceutical Sprague-Dawley Wound healing business Reactive Oxygen Species Polyglycolic Acid |
Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP Clinical science (London, England : 1979), vol 129, iss 12 |
Popis: | Burn wound healing involves a complex set of overlapping processes in an environment conducive to ischemia, inflammation, and infection costing $7.5 billion/year in the US 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 microparticles that provides a sustained release of bioactive insulin for >20days in a moist and protective environment. We hypothesized that insulin-containing ASD accelerates burn healing and stimulates a more regenerative, less scarring, healing. Using a heat-induced burn injury in rats, we show that burns treated with dressings containing 0.04mg insulin/cm2, every three days for 9 days, have faster closure, faster 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 burn dead tissue. We also observe faster resolution of the pro-inflammatory macrophages. We also found that insulin stimulates collagen deposition and maturation with the fibers organized more like a basket weave (normal skin) than aligned and crosslinked (scar tissue). In summary , application of ASD-containing insulin-loaded PLGA particles on burns every three 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. This work was supported by the National Natural Science Fund of China [grant numbers 81170761 and 81270909 (to Y.L.)]; the Natural Sciences and Engineering Research Council of Canada [grant numbers 204794-2011 (to M.H.) and private donor (to M.M.-G.)]. |
Databáze: | OpenAIRE |
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