Biodegradable and Antioxidant DNA Hydrogel as a Cytokine Delivery System for Diabetic Wound Healing
Biodegradable and Antioxidant DNA Hydrogel as a Cytokine Delivery System for Diabetic Wound Healing
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可生物降解和抗氧化的 DNA 水凝胶作为细胞因子递送系统用于糖尿病伤口愈合
DOI：
10.1002/adhm.202200782
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发表时间：
2022
影响因子：
10
通讯作者：
Chengshi Wang
中科院分区：
文献类型：
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作者：
Zhenghao Wang;W. Li;L. Gou;Ye Zhou;Ge Peng;Jiayi Zhang;Jiaye Liu;Ruoqing Li;Hengfan Ni;Wanli Zhang;Ting Cao;Qi Cao;Hong Su;Yuan;N. Tong;Xianghui Fu;E. Ilegems;Yan;P. Berggren;Xiaofeng Zheng;Chengshi Wang
糖尿病伤口愈合受损与慢性炎症和过度氧化应激的持续存在有关，这已成为最严重的临床挑战之一。具有抗炎和活性氧（ROS）清除特性的伤口敷料是糖尿病伤口治疗的理想选择。在这项研究中，通过将IL-33封装到物理交联的DNA水凝胶中，开发了一种形状适应性、可生物降解、生物相容性、抗氧化和免疫调节的白细胞介素-33（IL-33）-细胞凝胶，并用作伤口敷料，以促进糖尿病伤口愈合。IL-33-细胞凝胶的多孔微结构和可生物降解特性确保了IL-33在伤口区域的局部持续释放，其中IL-33的持续释放可维持至少7天。IL-33-细胞凝胶可诱导第2组先天性淋巴样细胞（ILC 2）和调节性T细胞（T细胞）的局部蓄积，以及伤口部位的M1至M2转化。此外，DNA水凝胶的抗氧化和生物相容性特征促进细胞内ROS的清除而不影响细胞活力。因此，在IL-33-细胞凝胶治疗后，糖尿病伤口区域的局部炎症得到解决，并伴随着肉芽组织再生的改善和伤口闭合的加速。这项研究通过结合DNA水凝胶和细胞因子免疫疗法来促进糖尿病伤口愈合，证明了组织工程和再生医学中一种有前途的策略。
Impaired diabetic wound healing is associated with the persistence of chronic inflammation and excessive oxidative stress, which has become one of the most serious clinical challenges. Wound dressings with anti‐inflammatory and reactive oxygen species (ROS)‐scavenging properties are desirable for diabetic wound treatment. In this study, a shape‐adaptable, biodegradable, biocompatible, antioxidant, and immunomodulatory interleukin‐33 (IL‐33)‐cytogel is developed by encapsulating IL‐33 into physically cross‐linked DNA hydrogels and used as wound dressings to promote diabetic wound healing. The porous microstructures and biodegradable properties of the IL‐33‐cytogel ensure the local sustained‐release of IL‐33 in the wound area, where the sustained‐release of IL‐33 is maintained for at least 7 days. IL‐33‐cytogel can induce local accumulation of group 2 innate lymphoid cells (ILC2s) and regulatory T cells (Tregs), as well as M1‐to‐M2 transition at the wound sites. Additionally, the antioxidant and biocompatible characteristics of DNA hydrogels promote the scavenging of intracellular ROS without affecting cell viability. As a result, local inflammation in the diabetic wound area is resolved upon IL‐33‐cytogel treatment, which is accompanied by improved granulation tissue regeneration and accelerated wound closure. This study demonstrates a promising strategy in tissue engineering and regenerative medicine by incorporating DNA hydrogels and cytokine immunotherapy for promoting diabetic wound healing.