Details

Autor(en) / Beteiligte

• Hauck, Sophia
• Zager, Paula
• Halfter, Norbert
• Wandel, Elke
• Torregrossa, Marta
• Kakpenova, Ainur
• Rother, Sandra
• Ordieres, Michelle
• Räthel, Susann
• Berg, Albrecht
• Möller, Stephanie
• Schnabelrauch, Matthias
• Simon, Jan C.
• Hintze, Vera
• Franz, Sandra

Titel

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

Ist Teil von

• Bioactive materials, 2021-12, Vol.6 (12), p.4342-4359

Ort / Verlag

China: Elsevier B.V

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. [Display omitted] •Sulfated hyaluronan (sHA) is a potent immunoregulatory artificial ECM component.•sHA controls inflammatory activites of macrophages via impeding TLR signaling.•sHA modulates pro-inflammatory macrophage activities in skin inflammation in mice.•sHA-releasing hydrogels switch macrophage activation in diabetic wounds in mice.•sHA-releasing hydrogels improve disturbed wound healing in diabetic mice.