Journal
BIOMATERIALS
Volume 98, Issue -, Pages 203-214Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.04.033
Keywords
Methacrylic acid; Sonic hedgehog; Macrophage polarization
Funding
- Ontario Research Foundation
- Natural Sciences and Engineering Research Council (NSERC)
- Province of Ontario
- University of Toronto
- NSERC Collaborative Research and Training Experience (CREATE) in Manufacturing Materials and Mimetics (M3) training program
- Canadian Institutes for Health Research
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Poly(methacrylic acid-co-methyl methacrylate) (MAA) beads promote a vascular regenerative response when used in diabetic wound healing. Previous studies reported that MAA beads modulated the expression of sonic hedgehog (Shh) and inflammation related genes in diabetic wounds. The aim of this work was to follow up on these observations in a subcutaneous injection model to study the host response in the absence of the confounding factors of diabetic wound healing. In this model, MM beads improved vascularization in healthy mice of both sexes compared to control poly(methyl methacrylate) (MM) beads, with a stronger effect seen in males than females. MAA-induced vessels were perfusable, as evidenced from the CLARITY-processed images. In Shh-Cre-eGFP/Ptch1LacZ non-diabetic transgenic mice, the increased vessel formation was accompanied by a higher density of cells expressing GFP (Shh) and beta-GaI (patched 1, Ptch1) suggesting MM enhanced the activation of the Shh pathway. Ptch1 is the Shh receptor and a target of the pathway. MAA beads also modulated the inflammatory cell infiltrate in CD1 mice: more neutrophils and more macrophages were noted with MM relative to MM beads at days 1 and 7, respectively. In addition, MAA beads biased macrophages towards a MHCII-CD206+ (M2) polarization state. This study suggests that the Shh pathway and an altered inflammatory response are two elements of the complex mechanism whereby MM-based biomaterials effect vascular regeneration. (C) 2016 Elsevier Ltd. All rights reserved.
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