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
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