Effects of structurally stabilized EGF and bFGF on wound healing in type I and type II diabetic mice

Seong Mi Choi, Kyoung Mi Lee, Hyun Jung Kim, Ik Kyu Park, Hwi Ju Kang, Hang Cheol Shin, Dawoon Baek, Yoorim Choi, Kwang Hwan Park, Jin Woo Lee

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Diabetes mellitus comprises a multiple metabolic disorder that affects millions of people worldwide and consequentially poses challenges for clinical treatment. Among the various complications, diabetic ulcer constitutes the most prevalent associated disorder and leads to delayed wound healing. To enhance wound healing capacity, we developed structurally stabilized epidermal growth factor (ST-EGF) and basic fibroblast growth factor (ST-bFGF) to overcome limitations of commercially available EGF (CA-EGF) and bFGF (CA-bFGF), such as short half-life and loss of activity after loading onto a matrix. Neither ST-EGF nor ST-bFGF was toxic, and both were more stable at higher temperatures than CA-EGF and CA-bFGF. We loaded ST-EGF and ST-bFGF onto a hyaluronate-collagen dressing (HCD) matrix, a biocompatible carrier, and tested the effectiveness of this system in promoting wound healing in a mouse model of diabetes. Wounds treated with HCD matrix loaded with 0.3 μg/cm2 ST-EGF or 1 μg/cm2 ST-bFGF showed a more rapid rate of tissue repair as compared to the control in type I and II diabetes models. Our results indicate that an HDC matrix loaded with 0.3 μg/cm2 ST-EGF or 1 μg/cm2 ST-bFGF can promote wound healing in diabetic ulcers and are suitable for use in wound dressings owing to their stability for long periods at room temperature. Statement of Significance Various types of dressing materials loaded with growth factors, such as VEGF, EGF, and bFGF, are widely used to effect wound repair. However, such growth factor-loaded materials have several limitations for use as therapeutic agents in healing-impaired diabetic wounds. To overcome these limitations, we have developed new materials containing structurally stabilized EGF (ST-EGF) and bFGF (ST-bFGF). To confirm the wound healing capacity of newly developed materials (ST-EGF and ST-bFGF-loaded hyaluronate-collagen dressing [HCD] matrix), we applied these matrices in type I and type II diabetic wounds. Notably, these matrices were able to accelerate wound healing including re-epithelialization, neovascularization, and collagen deposition. Consequentially, these ST-EGF and ST-bFGF-loaded HCD matrix may be used as future therapeutic agents in patients with diabetic foot ulcers.

Original languageEnglish
Pages (from-to)325-334
Number of pages10
JournalActa Biomaterialia
Volume66
DOIs
Publication statusPublished - 2018 Jan 15

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Epidermal Growth Factor
Wound Healing
Fibroblast Growth Factor 2
Fibroblasts
Bandages
Collagen
Medical problems
Wounds and Injuries
Ulcer
Intercellular Signaling Peptides and Proteins
Repair
Re-Epithelialization
Diabetic Foot
Temperature
Poisons
Proxy
Therapeutic Uses
Diabetes Complications
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus

All Science Journal Classification (ASJC) codes

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

Cite this

Choi, Seong Mi ; Lee, Kyoung Mi ; Kim, Hyun Jung ; Park, Ik Kyu ; Kang, Hwi Ju ; Shin, Hang Cheol ; Baek, Dawoon ; Choi, Yoorim ; Park, Kwang Hwan ; Lee, Jin Woo. / Effects of structurally stabilized EGF and bFGF on wound healing in type I and type II diabetic mice. In: Acta Biomaterialia. 2018 ; Vol. 66. pp. 325-334.
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abstract = "Diabetes mellitus comprises a multiple metabolic disorder that affects millions of people worldwide and consequentially poses challenges for clinical treatment. Among the various complications, diabetic ulcer constitutes the most prevalent associated disorder and leads to delayed wound healing. To enhance wound healing capacity, we developed structurally stabilized epidermal growth factor (ST-EGF) and basic fibroblast growth factor (ST-bFGF) to overcome limitations of commercially available EGF (CA-EGF) and bFGF (CA-bFGF), such as short half-life and loss of activity after loading onto a matrix. Neither ST-EGF nor ST-bFGF was toxic, and both were more stable at higher temperatures than CA-EGF and CA-bFGF. We loaded ST-EGF and ST-bFGF onto a hyaluronate-collagen dressing (HCD) matrix, a biocompatible carrier, and tested the effectiveness of this system in promoting wound healing in a mouse model of diabetes. Wounds treated with HCD matrix loaded with 0.3 μg/cm2 ST-EGF or 1 μg/cm2 ST-bFGF showed a more rapid rate of tissue repair as compared to the control in type I and II diabetes models. Our results indicate that an HDC matrix loaded with 0.3 μg/cm2 ST-EGF or 1 μg/cm2 ST-bFGF can promote wound healing in diabetic ulcers and are suitable for use in wound dressings owing to their stability for long periods at room temperature. Statement of Significance Various types of dressing materials loaded with growth factors, such as VEGF, EGF, and bFGF, are widely used to effect wound repair. However, such growth factor-loaded materials have several limitations for use as therapeutic agents in healing-impaired diabetic wounds. To overcome these limitations, we have developed new materials containing structurally stabilized EGF (ST-EGF) and bFGF (ST-bFGF). To confirm the wound healing capacity of newly developed materials (ST-EGF and ST-bFGF-loaded hyaluronate-collagen dressing [HCD] matrix), we applied these matrices in type I and type II diabetic wounds. Notably, these matrices were able to accelerate wound healing including re-epithelialization, neovascularization, and collagen deposition. Consequentially, these ST-EGF and ST-bFGF-loaded HCD matrix may be used as future therapeutic agents in patients with diabetic foot ulcers.",
author = "Choi, {Seong Mi} and Lee, {Kyoung Mi} and Kim, {Hyun Jung} and Park, {Ik Kyu} and Kang, {Hwi Ju} and Shin, {Hang Cheol} and Dawoon Baek and Yoorim Choi and Park, {Kwang Hwan} and Lee, {Jin Woo}",
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Choi, SM, Lee, KM, Kim, HJ, Park, IK, Kang, HJ, Shin, HC, Baek, D, Choi, Y, Park, KH & Lee, JW 2018, 'Effects of structurally stabilized EGF and bFGF on wound healing in type I and type II diabetic mice', Acta Biomaterialia, vol. 66, pp. 325-334. https://doi.org/10.1016/j.actbio.2017.11.045

Effects of structurally stabilized EGF and bFGF on wound healing in type I and type II diabetic mice. / Choi, Seong Mi; Lee, Kyoung Mi; Kim, Hyun Jung; Park, Ik Kyu; Kang, Hwi Ju; Shin, Hang Cheol; Baek, Dawoon; Choi, Yoorim; Park, Kwang Hwan; Lee, Jin Woo.

In: Acta Biomaterialia, Vol. 66, 15.01.2018, p. 325-334.

Research output: Contribution to journalArticle

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T1 - Effects of structurally stabilized EGF and bFGF on wound healing in type I and type II diabetic mice

AU - Choi, Seong Mi

AU - Lee, Kyoung Mi

AU - Kim, Hyun Jung

AU - Park, Ik Kyu

AU - Kang, Hwi Ju

AU - Shin, Hang Cheol

AU - Baek, Dawoon

AU - Choi, Yoorim

AU - Park, Kwang Hwan

AU - Lee, Jin Woo

PY - 2018/1/15

Y1 - 2018/1/15

N2 - Diabetes mellitus comprises a multiple metabolic disorder that affects millions of people worldwide and consequentially poses challenges for clinical treatment. Among the various complications, diabetic ulcer constitutes the most prevalent associated disorder and leads to delayed wound healing. To enhance wound healing capacity, we developed structurally stabilized epidermal growth factor (ST-EGF) and basic fibroblast growth factor (ST-bFGF) to overcome limitations of commercially available EGF (CA-EGF) and bFGF (CA-bFGF), such as short half-life and loss of activity after loading onto a matrix. Neither ST-EGF nor ST-bFGF was toxic, and both were more stable at higher temperatures than CA-EGF and CA-bFGF. We loaded ST-EGF and ST-bFGF onto a hyaluronate-collagen dressing (HCD) matrix, a biocompatible carrier, and tested the effectiveness of this system in promoting wound healing in a mouse model of diabetes. Wounds treated with HCD matrix loaded with 0.3 μg/cm2 ST-EGF or 1 μg/cm2 ST-bFGF showed a more rapid rate of tissue repair as compared to the control in type I and II diabetes models. Our results indicate that an HDC matrix loaded with 0.3 μg/cm2 ST-EGF or 1 μg/cm2 ST-bFGF can promote wound healing in diabetic ulcers and are suitable for use in wound dressings owing to their stability for long periods at room temperature. Statement of Significance Various types of dressing materials loaded with growth factors, such as VEGF, EGF, and bFGF, are widely used to effect wound repair. However, such growth factor-loaded materials have several limitations for use as therapeutic agents in healing-impaired diabetic wounds. To overcome these limitations, we have developed new materials containing structurally stabilized EGF (ST-EGF) and bFGF (ST-bFGF). To confirm the wound healing capacity of newly developed materials (ST-EGF and ST-bFGF-loaded hyaluronate-collagen dressing [HCD] matrix), we applied these matrices in type I and type II diabetic wounds. Notably, these matrices were able to accelerate wound healing including re-epithelialization, neovascularization, and collagen deposition. Consequentially, these ST-EGF and ST-bFGF-loaded HCD matrix may be used as future therapeutic agents in patients with diabetic foot ulcers.

AB - Diabetes mellitus comprises a multiple metabolic disorder that affects millions of people worldwide and consequentially poses challenges for clinical treatment. Among the various complications, diabetic ulcer constitutes the most prevalent associated disorder and leads to delayed wound healing. To enhance wound healing capacity, we developed structurally stabilized epidermal growth factor (ST-EGF) and basic fibroblast growth factor (ST-bFGF) to overcome limitations of commercially available EGF (CA-EGF) and bFGF (CA-bFGF), such as short half-life and loss of activity after loading onto a matrix. Neither ST-EGF nor ST-bFGF was toxic, and both were more stable at higher temperatures than CA-EGF and CA-bFGF. We loaded ST-EGF and ST-bFGF onto a hyaluronate-collagen dressing (HCD) matrix, a biocompatible carrier, and tested the effectiveness of this system in promoting wound healing in a mouse model of diabetes. Wounds treated with HCD matrix loaded with 0.3 μg/cm2 ST-EGF or 1 μg/cm2 ST-bFGF showed a more rapid rate of tissue repair as compared to the control in type I and II diabetes models. Our results indicate that an HDC matrix loaded with 0.3 μg/cm2 ST-EGF or 1 μg/cm2 ST-bFGF can promote wound healing in diabetic ulcers and are suitable for use in wound dressings owing to their stability for long periods at room temperature. Statement of Significance Various types of dressing materials loaded with growth factors, such as VEGF, EGF, and bFGF, are widely used to effect wound repair. However, such growth factor-loaded materials have several limitations for use as therapeutic agents in healing-impaired diabetic wounds. To overcome these limitations, we have developed new materials containing structurally stabilized EGF (ST-EGF) and bFGF (ST-bFGF). To confirm the wound healing capacity of newly developed materials (ST-EGF and ST-bFGF-loaded hyaluronate-collagen dressing [HCD] matrix), we applied these matrices in type I and type II diabetic wounds. Notably, these matrices were able to accelerate wound healing including re-epithelialization, neovascularization, and collagen deposition. Consequentially, these ST-EGF and ST-bFGF-loaded HCD matrix may be used as future therapeutic agents in patients with diabetic foot ulcers.

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