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Theranostics 2019; 9(1):65-76. doi:10.7150/thno.29766 This issue Cite

Research Paper

Engineering Bioactive Self-Healing Antibacterial Exosomes Hydrogel for Promoting Chronic Diabetic Wound Healing and Complete Skin Regeneration

Chenggui Wang^1*, Min Wang^2*, Tianzhen Xu¹, Xingxing Zhang³, Cai Lin³, Weiyang Gao¹, Huazi Xu¹, Bo Lei^2,4,5✉, Cong Mao^1✉

1. Key Laboratory of Orthopedics of Zhejiang Province, Department of Orthopedics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
2. Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an 710000, China
3. Center of Diabetic Foot, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
4. Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710054, China
5. Instrument Analysis Center, Xi'an Jiaotong University, Xi'an 710054, China
*These authors contributed equally to this work.

✉ Corresponding authors: maocongedu.cn (Cong Mao) and raybooedu.cn (Bo Lei).

Abstract

Rationale: Chronic nonhealing diabetic wound therapy and complete skin regeneration remains a critical clinical challenge. The controlled release of bioactive factors from a multifunctional hydrogel was a promising strategy to repair chronic wounds.

Methods: Herein, for the first time, we developed an injectable, self-healing and antibacterial polypeptide-based FHE hydrogel (F127/OHA-EPL) with stimuli-responsive adipose-derived mesenchymal stem cells exosomes (AMSCs-exo) release for synergistically enhancing chronic wound healing and complete skin regeneration. The materials characterization, antibacterial activity, stimulated cellular behavior and in vivo full-thickness diabetic wound healing ability of the hydrogels were performed and analyzed.

Results: The FHE hydrogel possessed multifunctional properties including fast self-healing process, shear-thinning injectable ability, efficient antibacterial activity, and long term pH-responsive bioactive exosomes release behavior. In vitro, the FHE@exosomes (FHE@exo) hydrogel significantly promoted the proliferation, migration and tube formation ability of human umbilical vein endothelial cells (HUVECs). In vivo, the FHE@exo hydrogel significantly enhanced the healing efficiency of diabetic full-thickness cutaneous wounds, characterized with enhanced wound closure rates, fast angiogenesis, re-epithelization and collagen deposition within the wound site. Moreover, the FHE@exo hydrogel displayed better healing outcomes than those of exosomes or FHE hydrogel alone, suggesting that the sustained release of exosomes and FHE hydrogel can synergistically facilitate diabetic wound healing. Skin appendages and less scar tissue also appeared in FHE@exo hydrogel treated wounds, indicating its potent ability to achieve complete skin regeneration.

Conclusion: This work offers a new approach for repairing chronic wounds completely through a multifunctional hydrogel with controlled exosomes release.

Keywords: multifunctional hydrogel, bioactive exosomes, responsive sustained release, diabetic wound healing

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