Multifunctional ADM hydrogel containing endothelial cell-exosomes for diabetic wound healing

Kaituo Xiang; Jing Chen; Jiahe Guo; Gongchi Li; Yu Kang; Cheng Wang; Tao Jiang; Maojie Zhang; Guoyong Jiang; Meng Yuan; Xuejiao Xiang; Yingpeng Xu; Sen Ren; Hewei Xiong; Xiang Xu; Wenqing Li; Xiaofan Yang; Zhenbing Chen

doi:10.1016/j.mtbio.2023.100863

Multifunctional ADM hydrogel containing endothelial cell-exosomes for diabetic wound healing

Mater Today Bio. 2023 Nov 13:23:100863. doi: 10.1016/j.mtbio.2023.100863. eCollection 2023 Dec.

Authors

Kaituo Xiang^{1

2

3}, Jing Chen^{4

5}, Jiahe Guo¹, Gongchi Li¹, Yu Kang¹, Cheng Wang¹, Tao Jiang¹, Maojie Zhang¹, Guoyong Jiang¹, Meng Yuan¹, Xuejiao Xiang¹, Yingpeng Xu¹, Sen Ren⁶, Hewei Xiong⁷, Xiang Xu¹, Wenqing Li⁸, Xiaofan Yang¹, Zhenbing Chen¹

Affiliations

¹ Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
² Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
³ The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, 325027, China.
⁴ Department of Dermatology, Wuhan No.1 Hospital, Wuhan, 430000, Hubei, China.
⁵ Hubei Province & Key Laboratory of Skin Infection and Immunity, Wuhan No.1 Hospital, Wuhan, 430022, Hubei, China.
⁶ Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
⁷ Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
⁸ Department of Hand and Foot Surgery, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518052, China.

Abstract

Non-healing wound, with limited treatment options, remains a prevalent complication of diabetes mellitus. The underlying causes wherein include oxidative stress injury, bacterial infection, cellular dysfunction, and persistent inflammation. Acellular Dermal Matrix (ADM), a wound dressing composed of natural extracellular matrix and abundant bioactive factors, has been successfully developed to treat various wounds, including burns and diabetic ulcers. Protocatechualdehyde (PA) & trivalent iron ion (Fe³⁺) complex (Fe³⁺@PA) exhibits potential antioxidant and antibacterial properties. In this study, we developed a dual hydrogel network by combining Fe³⁺@PA complex-modified ADM with light-cured gelatin (GelMA), supplemented with exosomes derived from human umbilical vein endothelial cells (HUVEC-Exos), to create an ADM composite hydrogel system (ADM-Fe³⁺@PA-Exos/GelMA) with antioxidant, antibacterial, and cell-promoting functions for diabetic wound treatment. Through in vitro experiments, we investigated the biosafety, antioxidant and antibacterial properties of ADM composite hydrogel. Furthermore, we examined the protective effects of ADM composite hydrogel on diabetic wound. The above experiments collectively demonstrate that our ADM-Fe³⁺@PA-Exos/GelMA hydrogel promotes diabetic wound healing by eliminating bacterial infection, reduced the reactive oxygen species (ROS) levels, protecting cells against oxidative stress damage, promotingcollagen deposition and angiogenesis, which provides a promising strategy to optimize ADM for diabetic wound treatment.

Keywords: Acellular dermal matrix; Diabetic wound healing; Exosomes; Hydrogel.