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 Zheng; Chengshi Wang

doi:10.1002/adhm.202200782

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 journal › Article › peer-review

57 Citations (Scopus)

235 Downloads (Pure)

Abstract

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 language	English
Article number	2200782
Number of pages	12
Journal	Advanced Healthcare Materials
Volume	11
Issue number	21
Early online date	13 Sept 2022
DOIs	https://doi.org/10.1002/adhm.202200782
Publication status	Published (in print/issue) - 2 Nov 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.

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. After initial online publication, the Author Contributions statement was amended on November 2, 2022, so that Z.W. and W.L., and P.-O.B., X.Z., and C.W. have their own, separate equal contributions statement.

Publisher Copyright:
© 2022 Wiley-VCH GmbH.

Keywords

diabetic wound healing
DNA hydrogels
IL-33
inflammation
reactive oxygen species
Reactive Oxygen Species
Cytokines
Interleukin-33
Humans
Hydrogels/chemistry
Inflammation
Wound Healing
Diabetes Mellitus
Immunity, Innate
Antioxidants
Lymphocytes
DNA
Delayed-Action Preparations

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/adhm.202200782

accepted versionAuthor Accepted Manuscript, 3.29 MB

Cite this

Wang, Z., Li, W., Gou, L., Zhou, Y., Peng, G., Zhang, J., Liu, J., Li, R., Ni, H., Zhang, W., Cao, T., Cao, Q., Su, H., Han, Y. P., Tong, N., Fu, X., Ilegems, E., Lu, Y., Berggren, P. O., ... Wang, C. (2022). Biodegradable and Antioxidant DNA Hydrogel as a Cytokine Delivery System for Diabetic Wound Healing. Advanced Healthcare Materials, 11(21), Article 2200782. https://doi.org/10.1002/adhm.202200782

@article{02c48d7c0ebc4260a74a3a988d678441,

title = "Biodegradable and Antioxidant DNA Hydrogel as a Cytokine Delivery System for Diabetic Wound Healing",

abstract = "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.",

keywords = "diabetic wound healing, DNA hydrogels, IL-33, inflammation, reactive oxygen species, Reactive Oxygen Species, Cytokines, Interleukin-33, Humans, Hydrogels/chemistry, Inflammation, Wound Healing, Diabetes Mellitus, Immunity, Innate, Antioxidants, Lymphocytes, DNA, Delayed-Action Preparations",

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

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. 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. After initial online publication, the Author Contributions statement was amended on November 2, 2022, so that Z.W. and W.L., and P.-O.B., X.Z., and C.W. have their own, separate equal contributions statement. Publisher Copyright: {\textcopyright} 2022 Wiley-VCH GmbH.",

year = "2022",

month = nov,

day = "2",

doi = "10.1002/adhm.202200782",

language = "English",

volume = "11",

journal = "Advanced Healthcare Materials",

issn = "2192-2640",

publisher = "John Wiley & Sons, Inc.",

number = "21",

}

Wang, Z, Li, W, Gou, L, Zhou, Y, Peng, G, Zhang, J, Liu, J, Li, R, Ni, H, Zhang, W, Cao, T, Cao, Q, Su, H, Han, YP, Tong, N, Fu, X, Ilegems, E, Lu, Y, Berggren, PO, Zheng, X & Wang, C 2022, 'Biodegradable and Antioxidant DNA Hydrogel as a Cytokine Delivery System for Diabetic Wound Healing', Advanced Healthcare Materials, vol. 11, no. 21, 2200782. https://doi.org/10.1002/adhm.202200782

TY - JOUR

T1 - Biodegradable and Antioxidant DNA Hydrogel as a Cytokine Delivery System for Diabetic Wound Healing

AU - Wang, Zhenghao

AU - Li, Wei

AU - Gou, Liping

AU - Zhou, Ye

AU - Peng, Ge

AU - Zhang, Jiayi

AU - Liu, Jiaye

AU - Li, Ruoqing

AU - Ni, Hengfan

AU - Zhang, Wanli

AU - Cao, Ting

AU - Cao, Qi

AU - Su, Hong

AU - Han, Yuan Ping

AU - Tong, Nanwei

AU - Fu, Xianghui

AU - Ilegems, Erwin

AU - Lu, Yanrong

AU - Berggren, Per Olof

AU - Zheng, Xiaofeng

AU - Wang, Chengshi

N1 - 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. 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. After initial online publication, the Author Contributions statement was amended on November 2, 2022, so that Z.W. and W.L., and P.-O.B., X.Z., and C.W. have their own, separate equal contributions statement. Publisher Copyright: © 2022 Wiley-VCH GmbH.

PY - 2022/11/2

Y1 - 2022/11/2

N2 - 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.

AB - 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.

KW - diabetic wound healing

KW - DNA hydrogels

KW - IL-33

KW - inflammation

KW - reactive oxygen species

KW - Reactive Oxygen Species

KW - Cytokines

KW - Interleukin-33

KW - Humans

KW - Hydrogels/chemistry

KW - Inflammation

KW - Wound Healing

KW - Diabetes Mellitus

KW - Immunity, Innate

KW - Antioxidants

KW - Lymphocytes

KW - DNA

KW - Delayed-Action Preparations

UR - http://www.scopus.com/inward/record.url?scp=85138674951&partnerID=8YFLogxK

U2 - 10.1002/adhm.202200782

DO - 10.1002/adhm.202200782

M3 - Article

C2 - 36101484

AN - SCOPUS:85138674951

SN - 2192-2640

VL - 11

JO - Advanced Healthcare Materials

JF - Advanced Healthcare Materials

IS - 21

M1 - 2200782

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this