Abstract
Collagen containing wound-care dressings are extensively used. However, the mechanism of action of these dressings remain unclear. Earlier studies utilizing a modified collagen gel (MCG) dressing demonstrated improved vascularization of ischemic wounds and better healing outcomes. Wound macrophages are pivotal in facilitating wound angiogenesis and timely healing. The current study was designed to investigate the effect of MCG on wound macrophage phenotype and function. MCG augmented recruitment of macrophage at the wound-site, attenuated pro-inflammatory and promoted anti-inflammatory macrophage polarization. Additionally, MCG increased anti-inflammatory IL-10, IL-4 and pro-angiogenic VEGF production, indicating a direct role of MCG in resolving wound inflammation and improving angiogenesis. At the wound-site, impairment in clearance of apoptotic cell bioburden enables chronic inflammation. Engulfment of apoptotic cells by macrophages (efferocytosis) resolves inflammation via a miR-21-PDCD4-IL-10 pathway. MCG-treated wound macrophages exhibited a significantly bolstered efferocytosis index. Such favorable outcome significantly induced miR-21 expression. MCG-mediated IL-10 production was dampened under conditions of miR-21 knockdown pointing towards miR-21 as a causative factor. Pharmacological inhibition of JNK attenuated IL-10 production by MCG, implicating miR-21-JNK pathway in MCG-mediated IL-10 production by macrophages. This work provides direct evidence demonstrating that a collagen-based wound-care dressing may influence wound macrophage function and therefore modify wound inflammation outcomes.
Highlights
IntroductionCollagen-based dressings are extensively used in wound care[11,12]
Collagen is biodegradable and possess weak antigenic properties[10]
To determine whether modified collagen gel (MCG) treatment affect the macrophage abundance at the wound-site during inflammatory phases, poly vinyl alcohol (PVA) sponges soaked in MCG stock solution were implanted subcutaneously in mice
Summary
Collagen-based dressings are extensively used in wound care[11,12]. These dressings are biocompatible, safe and applicable and can be combined with other modalities of care[13]. Modified collagen gel (MCG) is a bovine collagen based wound dressing. Using preclinical porcine models of excisional and ischemic wounds we have observed that MCG is effective in resolving inflammation and improving angiogenesis in these wounds[15,16]. Upon micro-environmental conditions, macrophages possess a wide range of functions which are modulated through the release of several factors[21]. We sought to evaluate the effect of MCG on macrophage function and polarization in the context of wound inflammation
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