Physically Cross-Linked DNA Hydrogel-Based Sustained Cytokine Delivery for In Situ Diabetic Alveolar Bone Rebuilding

Wei Li; Chengshi Wang; Zhenghao Wang; Liping Gou; Ye Zhou; Ge Peng; Min Zhu; Jiayi Zhang; Ruoqing Li; Hengfan Ni; Lei Wu; Wanli Zhang; Jiaye Liu; Yali Tian; Zhong Chen; Yuan-Ping Han; Nanwei Tong; Xianghui Fu; Xiaofeng Zheng; Per-Olof Berggren

doi:10.1021/acsami.2c04769

Physically Cross-Linked DNA Hydrogel-Based Sustained Cytokine Delivery for In Situ Diabetic Alveolar Bone Rebuilding

Wei Li, Chengshi Wang, Zhenghao Wang, Liping Gou, Ye Zhou, Ge Peng, Min Zhu, Jiayi Zhang, Ruoqing Li, Hengfan Ni, Lei Wu, Wanli Zhang, Jiaye Liu, Yali Tian, Zhong Chen, Yuan-Ping Han, Nanwei Tong, Xianghui Fu, Xiaofeng Zheng, Per-Olof Berggren

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Abstract

The development of a biodegradable and shape-adaptable bioscaffold that can enhance local cytokine retention and bioactivity is essential for the application of immunotherapy in periodontal diseases. Here, we report a biodegradable, anti-inflammatory, and osteogenic ILGel that uses a physically cross-linked DNA hydrogel as a soft bioscaffold for the long-term sustained release of cytokine interleukin-10 (IL-10) to accelerate diabetic alveolar bone rebuilding. Porous microstructures of ILGel favored the encapsulation of IL-10 and maintained IL-10 bioactivity for at least 7 days. ILGel can be gradually degraded or hydrolyzed under physiological conditions, avoiding the potential undesired side effects on dental tissues. Long-term sustained release of bioactive IL-10 from ILGel not only promoted M2 macrophage polarization and attenuated periodontal inflammation but also triggered osteogenesis of mesenchymal stem cells (MSCs), leading to accelerated alveolar bone formation and healing of alveolar bone defects under diabetic conditions in vivo. ILGel treatment significantly accelerated the defect healing rate of diabetic alveolar injury up to 93.42 ± 4.6% on day 21 post treatment compared to that of free IL-10 treatment (63.30 ± 7.39%), with improved trabecular architectures. Our findings imply the potential application of the DNA hydrogel as the bioscaffold for cytokine-based immunotherapy in diabetic alveolar bone injury and other periodontal diseases.

Original language	English
Pages (from-to)	25173-25182
Number of pages	10
Journal	ACS Applied Materials & Interfaces
Volume	14
Issue number	22
Early online date	31 May 2022
DOIs	https://doi.org/10.1021/acsami.2c04769
Publication status	Published (in print/issue) - 8 Jun 2022

Bibliographical note

Funding Information:
This study was supported by the National Natural Science Foundation of China (81801589, 82070846), the Center of Excellence-International Collaboration Initiative Grant of West China Hospital (139180012), the Program for Overseas High-Level Talents Introduction of Sichuan Province of China (21RCYJ0046), the China Postdoctoral Science Foundation (2018M643487, 2021TQ0225, 2021M702370), the Post-Doctor Research Project, West China Hospital of Sichuan University (2021HXBH065, 2019HXBH027), a Grant from Technology Innovation R & D Project of Chengdu Science and Technology Bureau (2019-YF05-01243-SN), and the 1.3.5 project for disciplines of excellence, West China Hospital of Sichuan University (ZYGD18017).

Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.

Keywords

Bone Regeneration
Cytokines
DNA
Delayed-Action Preparations
Diabetes Mellitus
Humans
Hydrogels/chemistry
Interleukin-10
Osteogenesis/genetics
Periodontal Diseases

UN SDGs

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

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10.1021/acsami.2c04769

Cite this

Li, W., Wang, C., Wang, Z., Gou, L., Zhou, Y., Peng, G., Zhu, M., Zhang, J., Li, R., Ni, H., Wu, L., Zhang, W., Liu, J., Tian, Y., Chen, Z., Han, Y.-P., Tong, N., Fu, X., Zheng, X., & Berggren, P.-O. (2022). Physically Cross-Linked DNA Hydrogel-Based Sustained Cytokine Delivery for In Situ Diabetic Alveolar Bone Rebuilding. ACS Applied Materials & Interfaces, 14(22), 25173-25182. https://doi.org/10.1021/acsami.2c04769

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title = "Physically Cross-Linked DNA Hydrogel-Based Sustained Cytokine Delivery for In Situ Diabetic Alveolar Bone Rebuilding",

abstract = "The development of a biodegradable and shape-adaptable bioscaffold that can enhance local cytokine retention and bioactivity is essential for the application of immunotherapy in periodontal diseases. Here, we report a biodegradable, anti-inflammatory, and osteogenic ILGel that uses a physically cross-linked DNA hydrogel as a soft bioscaffold for the long-term sustained release of cytokine interleukin-10 (IL-10) to accelerate diabetic alveolar bone rebuilding. Porous microstructures of ILGel favored the encapsulation of IL-10 and maintained IL-10 bioactivity for at least 7 days. ILGel can be gradually degraded or hydrolyzed under physiological conditions, avoiding the potential undesired side effects on dental tissues. Long-term sustained release of bioactive IL-10 from ILGel not only promoted M2 macrophage polarization and attenuated periodontal inflammation but also triggered osteogenesis of mesenchymal stem cells (MSCs), leading to accelerated alveolar bone formation and healing of alveolar bone defects under diabetic conditions in vivo. ILGel treatment significantly accelerated the defect healing rate of diabetic alveolar injury up to 93.42 ± 4.6% on day 21 post treatment compared to that of free IL-10 treatment (63.30 ± 7.39%), with improved trabecular architectures. Our findings imply the potential application of the DNA hydrogel as the bioscaffold for cytokine-based immunotherapy in diabetic alveolar bone injury and other periodontal diseases.",

keywords = "Bone Regeneration, Cytokines, DNA, Delayed-Action Preparations, Diabetes Mellitus, Humans, Hydrogels/chemistry, Interleukin-10, Osteogenesis/genetics, Periodontal Diseases",

author = "Wei Li and Chengshi Wang and Zhenghao Wang and Liping Gou and Ye Zhou and Ge Peng and Min Zhu and Jiayi Zhang and Ruoqing Li and Hengfan Ni and Lei Wu and Wanli Zhang and Jiaye Liu and Yali Tian and Zhong Chen and Yuan-Ping Han and Nanwei Tong and Xianghui Fu and Xiaofeng Zheng and Per-Olof Berggren",

note = "Funding Information: This study was supported by the National Natural Science Foundation of China (81801589, 82070846), the Center of Excellence-International Collaboration Initiative Grant of West China Hospital (139180012), the Program for Overseas High-Level Talents Introduction of Sichuan Province of China (21RCYJ0046), the China Postdoctoral Science Foundation (2018M643487, 2021TQ0225, 2021M702370), the Post-Doctor Research Project, West China Hospital of Sichuan University (2021HXBH065, 2019HXBH027), a Grant from Technology Innovation R & D Project of Chengdu Science and Technology Bureau (2019-YF05-01243-SN), and the 1.3.5 project for disciplines of excellence, West China Hospital of Sichuan University (ZYGD18017). Publisher Copyright: {\textcopyright} 2022 American Chemical Society. All rights reserved.",

year = "2022",

month = jun,

day = "8",

doi = "10.1021/acsami.2c04769",

language = "English",

volume = "14",

pages = "25173--25182",

journal = "ACS Applied Materials & Interfaces",

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Li, W, Wang, C, Wang, Z, Gou, L, Zhou, Y, Peng, G, Zhu, M, Zhang, J, Li, R, Ni, H, Wu, L, Zhang, W, Liu, J, Tian, Y, Chen, Z, Han, Y-P, Tong, N, Fu, X, Zheng, X & Berggren, P-O 2022, 'Physically Cross-Linked DNA Hydrogel-Based Sustained Cytokine Delivery for In Situ Diabetic Alveolar Bone Rebuilding', ACS Applied Materials & Interfaces, vol. 14, no. 22, pp. 25173-25182. https://doi.org/10.1021/acsami.2c04769

TY - JOUR

T1 - Physically Cross-Linked DNA Hydrogel-Based Sustained Cytokine Delivery for In Situ Diabetic Alveolar Bone Rebuilding

AU - Li, Wei

AU - Wang, Chengshi

AU - Wang, Zhenghao

AU - Gou, Liping

AU - Zhou, Ye

AU - Peng, Ge

AU - Zhu, Min

AU - Zhang, Jiayi

AU - Li, Ruoqing

AU - Ni, Hengfan

AU - Wu, Lei

AU - Zhang, Wanli

AU - Liu, Jiaye

AU - Tian, Yali

AU - Chen, Zhong

AU - Han, Yuan-Ping

AU - Tong, Nanwei

AU - Fu, Xianghui

AU - Zheng, Xiaofeng

AU - Berggren, Per-Olof

N1 - Funding Information: This study was supported by the National Natural Science Foundation of China (81801589, 82070846), the Center of Excellence-International Collaboration Initiative Grant of West China Hospital (139180012), the Program for Overseas High-Level Talents Introduction of Sichuan Province of China (21RCYJ0046), the China Postdoctoral Science Foundation (2018M643487, 2021TQ0225, 2021M702370), the Post-Doctor Research Project, West China Hospital of Sichuan University (2021HXBH065, 2019HXBH027), a Grant from Technology Innovation R & D Project of Chengdu Science and Technology Bureau (2019-YF05-01243-SN), and the 1.3.5 project for disciplines of excellence, West China Hospital of Sichuan University (ZYGD18017). Publisher Copyright: © 2022 American Chemical Society. All rights reserved.

PY - 2022/6/8

Y1 - 2022/6/8

N2 - The development of a biodegradable and shape-adaptable bioscaffold that can enhance local cytokine retention and bioactivity is essential for the application of immunotherapy in periodontal diseases. Here, we report a biodegradable, anti-inflammatory, and osteogenic ILGel that uses a physically cross-linked DNA hydrogel as a soft bioscaffold for the long-term sustained release of cytokine interleukin-10 (IL-10) to accelerate diabetic alveolar bone rebuilding. Porous microstructures of ILGel favored the encapsulation of IL-10 and maintained IL-10 bioactivity for at least 7 days. ILGel can be gradually degraded or hydrolyzed under physiological conditions, avoiding the potential undesired side effects on dental tissues. Long-term sustained release of bioactive IL-10 from ILGel not only promoted M2 macrophage polarization and attenuated periodontal inflammation but also triggered osteogenesis of mesenchymal stem cells (MSCs), leading to accelerated alveolar bone formation and healing of alveolar bone defects under diabetic conditions in vivo. ILGel treatment significantly accelerated the defect healing rate of diabetic alveolar injury up to 93.42 ± 4.6% on day 21 post treatment compared to that of free IL-10 treatment (63.30 ± 7.39%), with improved trabecular architectures. Our findings imply the potential application of the DNA hydrogel as the bioscaffold for cytokine-based immunotherapy in diabetic alveolar bone injury and other periodontal diseases.

AB - The development of a biodegradable and shape-adaptable bioscaffold that can enhance local cytokine retention and bioactivity is essential for the application of immunotherapy in periodontal diseases. Here, we report a biodegradable, anti-inflammatory, and osteogenic ILGel that uses a physically cross-linked DNA hydrogel as a soft bioscaffold for the long-term sustained release of cytokine interleukin-10 (IL-10) to accelerate diabetic alveolar bone rebuilding. Porous microstructures of ILGel favored the encapsulation of IL-10 and maintained IL-10 bioactivity for at least 7 days. ILGel can be gradually degraded or hydrolyzed under physiological conditions, avoiding the potential undesired side effects on dental tissues. Long-term sustained release of bioactive IL-10 from ILGel not only promoted M2 macrophage polarization and attenuated periodontal inflammation but also triggered osteogenesis of mesenchymal stem cells (MSCs), leading to accelerated alveolar bone formation and healing of alveolar bone defects under diabetic conditions in vivo. ILGel treatment significantly accelerated the defect healing rate of diabetic alveolar injury up to 93.42 ± 4.6% on day 21 post treatment compared to that of free IL-10 treatment (63.30 ± 7.39%), with improved trabecular architectures. Our findings imply the potential application of the DNA hydrogel as the bioscaffold for cytokine-based immunotherapy in diabetic alveolar bone injury and other periodontal diseases.

KW - Bone Regeneration

KW - Cytokines

KW - DNA

KW - Delayed-Action Preparations

KW - Diabetes Mellitus

KW - Humans

KW - Hydrogels/chemistry

KW - Interleukin-10

KW - Osteogenesis/genetics

KW - Periodontal Diseases

UR - http://www.scopus.com/inward/record.url?scp=85131772163&partnerID=8YFLogxK

U2 - 10.1021/acsami.2c04769

DO - 10.1021/acsami.2c04769

M3 - Article

C2 - 35638566

SN - 1944-8244

VL - 14

SP - 25173

EP - 25182

JO - ACS Applied Materials & Interfaces

JF - ACS Applied Materials & Interfaces

IS - 22

ER -

Physically Cross-Linked DNA Hydrogel-Based Sustained Cytokine Delivery for In Situ Diabetic Alveolar Bone Rebuilding

Abstract

Bibliographical note

Keywords

UN SDGs

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