Collagen/hyaluronan based hydrogels releasing sulfated hyaluronan improve dermal wound healing in diabetic mice via reducing inflammatory macrophage activity

Abstract

Sustained inflammation associated with dysregulated macrophage activation prevents tissue formation and healing of chronic wounds. Control of inflammation and immune cell functions thus represents a promising approach in the development of advanced therapeutic strategies. Here we describe immunomodulatory hyaluronan/collagen (HA-AC/coll)-based hydrogels containing high-sulfated hyaluronan (sHA) as immunoregulatory component for the modulation of inflammatory macrophage activities in disturbed wound healing. Solute sHA downregulates inflammatory activities of bone marrow-derived and tissue-resident macrophages in vitro . This further affects macrophage-mediated pro-inflammatory activation of skin cells as shown in skin ex-vivo cultures. In a mouse model of acute skin inflammation, intradermal injection of sHA downregulates the inflammatory processes in the skin. This is associated with the promotion of an anti-inflammatory gene signature in skin macrophages indicating a shift of their activation profile. For in vivo translation, we designed HA-AC/coll hydrogels allowing delivery of sHA into wounds over a period of at least one week. Their immunoregulatory capacity was analyzed in a translational experimental approach in skin wounds of diabetic db/db mice, an established model for disturbed wound healing. The sHA-releasing hydrogels improved defective tissue repair with reduced inflammation, augmented pro-regenerative macrophage activation, increased vascularization, and accelerated new tissue formation and wound closure.

Novel Trends in Hydrogel Development for Biomedical Applications: A Review

“…There are different types of COL (type I, II, III, IV and V, among others) present depending on their function in the body [ 165 ]. Thus, due to its abundance in nature, availability (porcine, bovine and marine), biodegradability and biocompatibility and excellent cell viability values (>80%), COL is an optimal candidate for hydrogel manufacture for wound healing [ 66 , 71 ], TE [ 67 , 72 ], drug delivery [ 68 ] and ophthalmic applications [ 73 ]. Nevertheless, even though ex vivo assays with COL-based hydrogels have been carried out with human skin models [ 71 ], more in vivo experiments are necessary to characterize COL-based hydrogels for other applications, for example, bone tissue engineering [ 72 ].…”

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Dual-Drug Loaded Biomimetic Chitosan-Collagen Hybrid Nanocomposite Scaffolds for Ameliorating Potential Tissue Regeneration in Diabetic Wounds

“…Multiple variables, including aberrant inflammatory retention and a diminished granulation tissue condition, cause wound healing to be delayed in people with diabetes. These factors primarily result from reduced glucose metabolic rate and neurovascular difficulties (5)(6)(7).…”