Biodegradable and Antioxidant DNA Hydrogel as a Cytokine Delivery System for Diabetic Wound Healing

Zhenghao Wang, Wei Li, Liping Gou, Ye Zhou, Ge Peng, Jiayi Zhang, Jiaye Liu, Ruoqing Li, Hengfan Ni, Wanli Zhang, Ting Cao, Qi Cao, Hong Su, Yuan Ping Han, Nanwei Tong, Xianghui Fu, Erwin Ilegems, Yanrong Lu, Per Olof Berggren, Xiaofeng ZhengChengshi Wang

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number2200782
Number of pages12
JournalAdvanced Healthcare Materials
Early online date13 Sep 2022
Publication statusPublished online - 13 Sep 2022

Bibliographical note

Funding Information:
This study was supported by the Program of National Natural Science Foundation of China (81801589, 82070846), Center of Excellence‐International Collaboration Initiative Grant of West China Hospital (139180012), Program for Overseas High‐Level Talents Introduction of Sichuan Province of China (2021JDGD0038), China Postdoctoral Science Foundation (2018M643487, 2021TQ0225, 2021M702370), the Post‐Doctor Research Project, West China Hospital of Sichuan University (2019HXBH027), Grant from Technology Innovation R & D Project of Chengdu Science and Technology Bureau (2019‐YF05‐01243‐SN), Program of Natural Science Foundation of Sichuan (2022NSFSC1559, 2022NSFSC1569), 1.3.5 project for disciplines of excellence, West China Hospital of Sichuan University (ZYGD18017), the Swedish Research Council and European Research Council grant ERC‐2018‐AdG 834860 EYELETS.

Publisher Copyright:
© 2022 Wiley-VCH GmbH.


  • diabetic wound healing
  • DNA hydrogels
  • IL-33
  • inflammation
  • reactive oxygen species


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