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, jinwoo lee

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)59-68
Number of pages10
JournalActa Biomaterialia
Volume38
DOIs
Publication statusPublished - 2016 Jul 1

Fingerprint

Hydrogels
Hydrogel
Gelatin
Bandages
Chemokines
Wound Healing
Interleukin-8
Wounds and Injuries
Horseradish Peroxidase
Re-Epithelialization
Macrophage Inflammatory Proteins
Therapeutics
Topical Administration
Granulation
Proteins
Streptozocin

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

Cite this

Yoon, Dong Suk ; Lee, Yunki ; Ryu, Hyun Aae ; Jang, Yeonsue ; Lee, Kyoung Mi ; Choi, Yoorim ; Choi, Woo Jin ; Lee, Moses ; Park, Kyung Min ; Park, Ki Dong ; lee, jinwoo. / Cell recruiting chemokine-loaded sprayable gelatin hydrogel dressings for diabetic wound healing. In: Acta Biomaterialia. 2016 ; Vol. 38. pp. 59-68.
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title = "Cell recruiting chemokine-loaded sprayable gelatin hydrogel dressings for diabetic wound healing",
abstract = "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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Yoon, DS, Lee, Y, Ryu, HA, Jang, Y, Lee, KM, Choi, Y, Choi, WJ, Lee, M, Park, KM, Park, KD & lee, J 2016, 'Cell recruiting chemokine-loaded sprayable gelatin hydrogel dressings for diabetic wound healing', Acta Biomaterialia, vol. 38, pp. 59-68. https://doi.org/10.1016/j.actbio.2016.04.030

Cell recruiting chemokine-loaded sprayable gelatin hydrogel dressings for diabetic wound healing. / Yoon, Dong Suk; Lee, Yunki; Ryu, Hyun Aae; Jang, Yeonsue; Lee, Kyoung Mi; Choi, Yoorim; Choi, Woo Jin; Lee, Moses; Park, Kyung Min; Park, Ki Dong; lee, jinwoo.

In: Acta Biomaterialia, Vol. 38, 01.07.2016, p. 59-68.

Research output: Contribution to journalArticle

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T1 - Cell recruiting chemokine-loaded sprayable gelatin hydrogel dressings for diabetic wound healing

AU - Yoon, Dong Suk

AU - Lee, Yunki

AU - Ryu, Hyun Aae

AU - Jang, Yeonsue

AU - Lee, Kyoung Mi

AU - Choi, Yoorim

AU - Choi, Woo Jin

AU - Lee, Moses

AU - Park, Kyung Min

AU - Park, Ki Dong

AU - lee, jinwoo

PY - 2016/7/1

Y1 - 2016/7/1

N2 - 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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