Engineering Bioactive Self-Healing Antibacterial Exosomes Hydrogel for Promoting Chronic Diabetic Wound Healing and Complete Skin Regeneration
Authors: Weiyang Gao
Chenggui Wang
Xingxing Zhang
Huazi Xu
Cai Lin
Cong Mao
Min Wang
Bo Lei
Tianzhen Xu
Journal: Theranostics (2019)
Discipline: CLINICAL MEDICINE
Keywords: bioactive exosomes; diabetic wound healing; multifunctional hydrogel; responsive sustained release.
Affiliations: 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., Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an 710000, China., Center of Diabetic Foot, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China., Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710054, China., Instrument Analysis Center, Xi'an Jiaotong University, Xi'an 710054, China.

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. 

Retracted: No

PubPeer comments:
 Figure 4B was brought to my attention by a reader. It looks similar to Figure 7B of Min Wang et al. ACS Nano 2019, 13, 10279u221210293, DOI: 10.1021 acsnano.9b03656 , from the same research group. See: https: pubpeer.com publications 68052D5E8EE1E66ACB9A6857279E47 Could the authors please share the individual measurements, please? ![file] , 
 Two panels in Figure 5 of this paper also appear to overlap with panels in Figure 8 of the Min Wang et al. paper, although they represent different nanomaterial treatments. ![file] , 
 Erratum, November 2021: https: www.thno.org v11p10174.htm  *The authors regret that some incorrect representative images were accidentally used in our previously published paper [1] when the first author assembled the figures, which are the wound healing image of Control at Day 0 in Figure 4A, the immunohistochemical staining of Collagen I (FHE@exo group at Day 21) in Figure 5A and Collagen III (FHE group at Day 21) in Figure 5C, and the immunohistochemical staining of Ki67 (FHE group at Day 14) in Figure S6C. The correct representative images are shown below. The corrections made in this erratum do not affect any of the results, conclusion and the text description in the original published version. The authors express sincere apologies for any inconvenience or misunderstanding that it may have caused.* ,