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



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.
Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul 120-752, South Korea.
Dong Suk
DS
Yoon
Department of Molecular Science and Technology, Ajou University, Suwon 443-749, South Korea.
Yunki
Y
Lee
Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul 120-752, South Korea.
Hyun Aae
HA
Ryu
Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul 120-752, South Korea.
Yeonsue
Y
Jang
Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul 120-752, South Korea; Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, South Korea.
Kyoung-Mi
KM
Lee
Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul 120-752, South Korea; Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, South Korea.
Yoorim
Y
Choi
Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul 120-752, South Korea.
Woo Jin
WJ
Choi
Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul 120-752, South Korea.
Moses
M
Lee
Division of Bioengineering, Incheon National University, Incheon 406-772, South Korea.
Kyung Min
KM
Park
Department of Molecular Science and Technology, Ajou University, Suwon 443-749, South Korea.
Ki Dong
KD
Park
Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul 120-752, South Korea; Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, South Korea. Electronic address: ljwos@yuhs.ac.
Jin Woo
JW
Lee
D000818:Animals; D054418:Chemokine CCL20 / Q000737:chemistry / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D016503:Drug Delivery Systems / Q000379:methods*; D005780:Gelatin / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology; D016209:Interleukin-8 / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000188:drug therapy*
C108355:CCL20 protein, human; C508606:CXCL8 protein, human; D054418:Chemokine CCL20; D020100:Hydrogels; D016209:Interleukin-8; D005780:Gelatin
Chemokine; Diabetes; Hydrogel dressings; In situ forming hydrogels; Wound healing