Collagen/hyaluronan based hydrogels releasing sulfated hyaluronan improve dermal wound healing in diabetic mice via reducing inflammatory macrophage activity.
Collagen/hyaluronan based hydrogels releasing sulfated hyaluronan improve dermal wound healing in diabetic mice via reducing inflammatory macrophage activity.
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DOI：
10.1016/j.bioactmat.2021.04.026
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发表时间：
2021-12
影响因子：
18.9
通讯作者：
Franz S
中科院分区：
文献类型：
--
作者：
Hauck S;Zager P;Halfter N;Wandel E;Torregrossa M;Kakpenova A;Rother S;Ordieres M;Räthel S;Berg A;Möller S;Schnabelrauch M;Simon JC;Hintze V;Franz S
与巨噬细胞激活失调相关的持续炎症会阻止慢性伤口的组织形成和愈合。因此，控制炎症和免疫细胞功能代表了发展先进治疗策略的有希望的方法。在这里，我们描述了含有高硫酸透明质酸（sHA）的免疫调节透明质酸/胶原（HA-AC/coll）为基础的水凝胶，作为调节炎症性巨噬细胞活性的免疫调节成分。溶质sHA在体外下调骨髓源性和组织内巨噬细胞的炎症活性。这进一步影响巨噬细胞介导的皮肤细胞促炎激活，如皮肤离体培养所示。在小鼠急性皮肤炎症模型中，皮内注射sHA可下调皮肤炎症过程。这与皮肤巨噬细胞中抗炎基因特征的促进有关，表明它们的激活谱发生了变化。对于体内翻译，我们设计了HA-AC/coll水凝胶，允许sHA在至少一周的时间内进入伤口。在糖尿病db/db小鼠（一种已建立的创伤愈合紊乱模型）的皮肤伤口中，通过翻译实验方法分析了它们的免疫调节能力。释放sha的水凝胶通过减少炎症、增强促再生巨噬细胞激活、增加血管化、加速新组织形成和伤口愈合来改善缺陷组织修复。硫酸透明质酸（sHA）是一种有效的免疫调节人工ECM成分。sHA通过阻断TLR信号传导来控制巨噬细胞的炎症活性。sHA可调节小鼠皮肤炎症中的促炎巨噬细胞活性。释放sha的水凝胶可改变小鼠糖尿病伤口中巨噬细胞的激活。释放sha的水凝胶改善糖尿病小鼠的创伤愈合。
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. 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.
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影响因子：
17.1
作者：
Eming SA;Martin P;Tomic-Canic M
通讯作者：
Tomic-Canic M
DOI：
10.1084/jem.20141539
发表时间：
2015-04-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dal-Secco D;Wang J;Zeng Z;Kolaczkowska E;Wong CH;Petri B;Ransohoff RM;Charo IF;Jenne CN;Kubes P
通讯作者：
Kubes P
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ
DOI：
10.1016/j.bbalip.2019.04.001
发表时间：
2019-07-01
影响因子：
4.8
作者：
Gianfrancesco, Marco A.;Dehairs, Jonas;Legrand-Poels, Sylvie
通讯作者：
Legrand-Poels, Sylvie
影响因子：
9.7
作者：
Franz, Sandra;Allenstein, Francie;Simon, Jan C.
通讯作者：
Simon, Jan C.