Topical α‐gal nanoparticles accelerate diabetic wound healing

Abstract

An inadequate response from macrophages, key orchestrators of the wound healing process, has been implicated in the pathophysiology of impaired healing in diabetes. This study explored the utility of nanoparticles presenting the α‐gal (Galα1‐3Galβ1‐4GlcNAc‐R) epitope to induce anti‐Gal antibody‐mediated local transient recruitment of macrophages to accelerate wound closure and healing in a diabetic murine model. α1,3galactosyltrasferase knockout mice were stimulated to produce anti‐Gal antibodies and subsequently diabetes was induced by streptozotocin‐induced β‐cell destruction. Six mm full‐thickness skin wounds were made and α‐gal nanoparticles (AGN) were topically applied on postwounding days 0 and 1. Wounds were analysed histologically for macrophage invasion and markers of wound healing, including epithelialization, vascularization and granulation tissue deposition through postoperative day 12. We found that application of AGN transiently but significantly increased macrophage recruitment into the wounds of diabetic mice. Treated wounds demonstrated more rapid closure and enhanced wound healing as demonstrated by significantly accelerated rates of epithelialization, vascularization and granulation tissue deposition. Thus, topical treatment of full‐thickness wounds in diabetic mice with α‐gal nanoparticles induced a transient but significant increase in macrophage recruitment resulting in an accelerated rate of wound healing. Using α‐gal nanoparticles as a topical wound healing adjunct is a simple, safe and effective means of augmenting dysregulated macrophage recruitment present in the diabetic state.

Near Complete Repair After Myocardial Infarction in Adult Mice by Altering the Inflammatory Response With Intramyocardial Injection of α-Gal Nanoparticles

“…Nevertheless, extensive macrophages infiltration is also observed in untreated (control) post-MI hearts in adult mice ( 4 – 6 , 51 , 55 , 56 ). Both mouse macrophages infiltrating into untreated post-MI hearts ( 51 , 55 ) and macrophages recruited by α-gal nanoparticles in sponge disc implants ( 29 ) were found to display M2 polarization. In view of these observations, the polarization state of the infiltrating macrophages in post-MI hearts treated with by α-gal nanoparticles was not determined.…”

More than just bricks and mortar: Fibroblasts and ECM in skin health and disease

“…Authors discuss promoting and deleterious effects of cellular senescence on wound healing and the underlying mechanisms that can be both direct, via senescence in fibroblasts and indirect, via senescence in wound‐resident macrophages. Dysfunctions in macrophage secretome, that normally contains wound healing‐promoting factors, 24,25 can have profound effects on skin fibroblast behaviour.…”

Contribuições Do Enfermeiro Na Pesquisa Básica: Modelo De Fixação De Curativo Em Feridas Cutâneas Excisionais De Camundongos

“…Dentre os estudos experimentais publicados, alguns descreveram formas de fixação de curativo em modelos animais 10,16,17 que serviram de apoio e orientação para padronização do modelo de curativos empregado neste estudo em questão.…”

“…A seguir, as feridas foram ocluídas com filme transparente Tegaderm TM (3M®) e os animais envolvidos circunferencialmente com atadura autoaderente Coban TM (3M®). A agregação da cobertura e atadura apresentou capacidade de manter as nanopartículas sobre a ferida 17 .…”