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

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

作者机构：Department of DermatologyVenerology und AllergologyLeipzig University04103LeipzigGermany Institute of Materials ScienceMax Bergmann Center for BiomaterialsTechnische Universitǎt Dresden01069DresdenGermany Biomaterials DepartmentINNOVENT e.V.JenaGermany 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2021年第6卷第12期

页      面：4342-4359页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 081702[工学-化学工艺] 08[工学] 0817[工学-化学工程与技术] 0836[工学-生物工程] 

基　　金：This work was funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)project number 59307082-TRR67 subprojects A3,B3,Z3 project FR2671/4-1 to SF project 420160411 to SR 

主　　题：4-6):sulfated hyaluronan Macrophages Immunomodulation Chronic wounds Hydrogel Skin inflammation 

摘      要：Sustained inflammation associated with dysregulated macrophage activation prevents tissue formation and healing of chronic *** of inflammation and immune cell functions thus represents a promising approach in the development of advanced therapeutic *** 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 *** sHA downregulates inflammatory activities of bone marrow-derived and tissue-resident macrophages in *** further affects macrophage-mediated pro-inflammatory activation of skin cells as shown in skin ex-vivo *** a mouse model of acute skin inflammation,intradermal injection of sHA downregulates the inflammatory processes in the *** is associated with the promotion of an anti-inflammatory gene signature in skin macrophages indicating a shift of their activation *** in vivo translation,we designed HA-AC/coll hydrogels allowing delivery of sHA into wounds over a period of at least one *** immunoregulatory capacity was analyzed in a translational experimental approach in skin wounds of diabetic db/db mice,an established model for disturbed wound *** 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.