Spermidine-Functionalized Injectable Hydrogel Reduces Inflammation and Enhances Healing of Acute and Diabetic Wounds In Situ,Advanced Science

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Spermidine-Functionalized Injectable Hydrogel Reduces Inflammation and Enhances Healing of Acute and Diabetic Wounds In Situ
Advanced Science ( IF 14.3 ) Pub Date : 2024-04-11 , DOI: 10.1002/advs.202310162
Qianqian Wu ₁ , Runjiao Yang ₁ , Wenxuan Fan ₁ , Li Wang ₁ , Jing Zhan ₂ , Tingting Cao ₂ , Qiming Liu ₁ , Xianshu Piao ₁ , Yinghui Zhong ₁ , Wenxian Zhao ₁ , Shuhan Zhang ₁ , Jiaao Yu ₃ , Song Liang ₁ , Thomas M Roberts _{4,

5} , Bingdi Wang ₁ , Zhenning Liu ₁

Affiliation

The inflammatory response is a key factor affecting tissue regeneration. Inspired by the immunomodulatory role of spermidine, an injectable double network hydrogel functionalized with spermidine (DN-SPD) is developed, where the first and second networks are formed by dynamic imine bonds and non-dynamic photo-crosslinked bonds respectively. The single network hydrogel before photo-crosslinking exhibits excellent injectability and thus can be printed and photo-crosslinked in situ to form double network hydrogels. DN-SPD hydrogel has demonstrated desirable mechanical properties and tissue adhesion. More importantly, an “operando” comparison of hydrogels loaded with spermidine or diethylenetriamine (DETA), a sham molecule resembling spermidine, has shown similar physical properties, but quite different biological functions. Specifically, the outcomes of 3 sets of in vivo animal experiments demonstrate that DN-SPD hydrogel can not only reduce inflammation caused by implanted exogenous biomaterials and reactive oxygen species but also promote the polarization of macrophages toward regenerative M2 phenotype, in comparison with DN-DETA hydrogel. Moreover, the immunoregulation by spermidine can also translate into faster and more natural healing of both acute wounds and diabetic wounds. Hence, the local administration of spermidine affords a simple but elegant approach to attenuate foreign body reactions induced by exogenous biomaterials to treat chronic refractory wounds.

中文翻译：

亚精胺功能化可注射水凝胶可减少炎症并促进急性和糖尿病伤口的原位愈合

炎症反应是影响组织再生的关键因素。受亚精胺免疫调节作用的启发，开发了一种亚精胺功能化的可注射双网络水凝胶（DN-SPD），其中第一和第二网络分别由动态亚胺键和非动态光交联键形成。光交联前的单网络水凝胶表现出优异的可注射性，因此可以原位印刷和光交联形成双网络水凝胶。 DN-SPD 水凝胶已表现出理想的机械性能和组织粘附性。更重要的是，对装载有亚精胺或二乙烯三胺（DETA）（一种类似于亚精胺的假分子）的水凝胶进行“操作”比较，显示出相似的物理特性，但生物学功能却截然不同。具体来说，三组体内动物实验的结果表明，与DN-DETA相比，DN-SPD水凝胶不仅可以减少植入的外源生物材料和活性氧引起的炎症，还可以促进巨噬细胞向再生M2表型极化水凝胶。此外，亚精胺的免疫调节还可以转化为急性伤口和糖尿病伤口更快、更自然的愈合。因此，亚精胺的局部给药提供了一种简单而优雅的方法来减弱外源性生物材料引起的异物反应，以治疗慢性难治性伤口。

更新日期：2024-04-11

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