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Cell recruiting chemokine-loaded sprayable gelatin hydrogel dressings for diabetic wound healing.

 Dong Suk Yoon  ;  Yunki Lee  ;  Hyun Aae Ryu  ;  Yeonsue Jang  ;  Kyoung-Mi Lee  ;  Yoorim Choi  ;  Woo Jin Choi  ;  Moses Lee  ;  Kyung Min Park  ;  Ki Dong Park  ;  Jin Woo Lee 
 Acta Biomaterialia, Vol.38 : 59-68, 2016 
Journal Title
 Acta Biomaterialia 
Issue Date
Animals ; Chemokine CCL20*/chemistry ; Chemokine CCL20*/pharmacology ; Diabetes Mellitus, Experimental/drug therapy* ; Drug Delivery Systems/methods* ; Gelatin*/chemistry ; Gelatin*/pharmacology ; Humans ; Hydrogels*/chemistry ; Hydrogels*/pharmacology ; Interleukin-8*/chemistry ; Interleukin-8*/pharmacology ; Mice ; Mice, Inbred ICR ; Wound Healing/drug effects* ; Wounds and Injuries/drug therapy*
Chemokine ; Diabetes ; Hydrogel dressings ; In situ forming hydrogels ; Wound healing
In this study, we developed horseradish peroxidase (HRP)-catalyzed sprayable gelatin hydrogels (GH) as a bioactive wound dressing that can deliver cell-attracting chemotactic cytokines to the injured tissues for diabetic wound healing. We hypothesized that topical administration of chemokines using GH hydrogels might improve wound healing by inducing recruitment of the endogenous cells. Two types of chemokines (interleukin-8; IL-8, macrophage inflammatory protein-3α; MIP-3α) were simply loaded into GH hydrogels during in situ cross-linking, and then their wound-healing effects were evaluated in streptozotocin-induced diabetic mice. The incorporation of chemokines did not affect hydrogels properties including swelling ratio and mechanical stiffness, and the bioactivities of IL-8 and MIP-3α released from hydrogel matrices were stably maintained. In vivo transplantation of chemokine-loaded GH hydrogels facilitated cell infiltration into the wound area, and promoted wound healing with enhanced re-epithelialization/neovascularization and increased collagen deposition, compared with no treatment or the GH hydrogel alone. Based on our results, we suggest that cell-recruiting chemokine-loaded GH hydrogel dressing can serve as a delivery platform of various therapeutic proteins for wound healing applications. STATEMENT OF SIGNIFICANCE: Despite development of materials combined with therapeutic agents for diabetic wound treatment, impaired wound healing by insufficient chemotactic responses still remain as a significant problem. In this study, we have developed enzyme-catalyzed gelatin (GH) hydrogels as a sprayable dressing material that can deliver cell-attracting chemokines for diabetic wound healing. The chemotactic cytokines (IL-8 and MIP-3α) were simply loaded within hydrogel during in situ gelling, and wound healing efficacy of chemokine-loaded GH hydrogels was investigated in STZ-induced diabetic mouse model. These hydrogels significantly promoted wound-healing efficacy with faster wound closure, neovascularization, and thicker granulation. Therefore, we expect that HRP-catalyzed in situ forming GH hydrogels can serve as an injectable/sprayable carrier of various therapeutic agents for wound healing applications.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
Yonsei Authors
이경미(Lee, Kyoung Mi) ORCID logo https://orcid.org/0000-0002-9038-8162
이모세(Lee, Mo Ses)
이진우(Lee, Jin Woo) ORCID logo https://orcid.org/0000-0002-0293-9017
장연수(Jang, Yeon Sue) ORCID logo https://orcid.org/0000-0001-5683-0001
최우진(Choi, Woo Jin)
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