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최성미(정형외과학교실) Acta Biomater
등록일 : 2017-12-07 오후 2:55:00       조회 : 24
첨   부 :
제1저자 최성미(정형외과학교실, BK21)
교선저자 이진우(정형외과학교실)
Acta Biomater. 2017 Dec 1. pii: S1742-7061(17)30742-0. doi: 10.1016/j.actbio.2017.11.045. [Epub ahead of print]

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

Choi SM1, Lee KM2, Kim HJ3, Park IK3, Kang HJ3, Shin HC4, Baek D1, Choi Y1, Park KH5, Lee JW6.

Author information
1Department of Orthopaedic Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea; Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea.2Department of Orthopaedic Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea.3R&D Center, Genewel Co., Ltd., Sungnam 13211, South Korea.4School of Systems Biomedical Science, Soongsil University, Seoul 156-743, South Korea.5Department of Orthopaedic Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea.6Department of Orthopaedic Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea; Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea. Electronic address: ljwos@yuhs.ac.

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.
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