P030 : Encouraging results of wound healing in diabetic mouse: autologously cultured dermal fibroblasts showed better wound healing on the diabetic mouse skin ulcers than nonself stem cell

( Ji Hae Lee ),( Jung Min Bae ),( Eu Seok Chung ),( Hanmi Chung ),( Sae Mi Park ),( Ju Hee Lee ),( Hee Jin Jeon ),( Seung Jun Hwang ),( Gyong Moon Kim ) 대한피부과학회 2014 대한피부과학회 학술발표대회집 Vol.66 No.2

Background: The Immunologically privileged autologously cultured dermal fibroblasts of diabetic mouse may have same or better functions than normally working fibroblasts or stem cells, and previous reports showed similar functioning abilities of diabetic dermal fibroblasts compared with that of normal origin. Objectives: We would like to show that immunologically privileged autologously sampled and cultured dermal fibroblasts might show better clinical and histological, immunohistochemical results than allogeneic mesenchymal stem cells in cell transplantation therapy for diabetic skin ulcers. Methods: Every mouse was given surgery which procedure resulted in 6 mm identical full thickness wound in both back area, and A group mouse were injected allogeneic normal stem cells in right-sided wounds with left sided wounds untreated (normal control). Simultaneously, B group mouse were injected autologous diabetic fibroblasts in right-sided wounds with left sided wounds untreated (normal control). Results: Compared with bare diabetic wounds and groups of diabetic wounds treated with allogeneic stem cells as control groups, autologous fibroblasts-transplanted diabetic wounds showed better wound healing with better, faster dermal granulation tissue regeneration and vascularization than allogeneic stem cell treated wounds. Conclusion: Immunologically privileged autologous dermal fibroblasts may be good therapeutics in nonhealing chronic, diabetic skin ulcers.

Effect of Vitamin A on Early Wound Healing in Diabetic Rats

Byeon, Jun Hee,Lee, Chong Kun,Hur, Gene,Kang, Yoon Jae,Rhie, Jong Won,Lim, Poong CATHOLIC MEDICAL CENTER 1996 Bulletin of the Clinical Research Institute Vol.24 No.2

Diabetes mellitus is a complex metabolic disorder of which components have several direct and indirect effects on wound healing. The inhibition mechanism of diabetes mellitus on wound healing remains unclear. Some previous studies on the relationships between vitamin A and the biological control of wound healing have shown that vitamin A increases inflammatory reaction by exerting an effect upon inflammatory cells in the early phase of wound healing, but the physiological action and the mechanism of vitamin A on wound healing in diabetic patients remains unclear. This study was undertaken to investigate the efficacy of vitamin A on delayed wound healing in diabetes mellitus. The experimental animals were ninety six Wistar rats, which were divided into four groups : normal control group, normal-vitamin A treated group, diabetic group, and vitamin A treated diabetic group. Experimental diabetes mellitus was induced by intravenous injection with streptozotocin (50㎎/㎏). An incisional wound about 5 cm in length was made on the back and was closed primarily. The normal-vitamin A treated group and diabetic-vitamin A treated group were received vitamin A intramuscularly in dose of 1000IU/㎏ once daily after operation. To compare the wound healing of each group, wound burst strength and histological findings were evaluated on the 3rd, 5th, 7th, and 14th postoperative days. The results were as follows; 1. The wound healing in diabetic group was delayed compared with that of normal control group grossly. 2. Wound burst strength was increased gradually as days elapsed in all groups and the increasing tendency of it in the diabetic group was less than that of the other groups. Wound burst strength in diabetic group was significantly less than that of normal control group on 5th, 7th, and 14th postoperative days(P<0.001). 3. Histologically, the amounts of collagen deposition and the numbers of infiltrated leukocytes were slightly decreased in the diabetic group and were slightly increased in the vitamin A treated diabetic group at 7th and 14th day postoperatively compared with those of the normal control groups. These results suggest that vitamin A treatment has beneficial influence on wound healing in the diabetes mellitus.

PVA/PVP Nanofibres Incorporated with Ecklonia cava Phlorotannins Exhibit Excellent Cytocompatibility and Accelerate Hyperglycaemic Wound Healing

Phang Shou Jin,Teh Huey Xhin,Looi Mee Lee,Fauzi Mh Busra,Neo Yun Ping,Arumugam Bavani,Kuppusamy Umah Rani 한국조직공학과 재생의학회 2024 조직공학과 재생의학 Vol.21 No.2

Background: Diabetic foot ulcer (DFU) is a major debilitating complication of diabetes. The lack of effective diabetic wound dressings has been a significant problem in DFU management. In this study, we aim to establish a phlorotannin-incorporated nanofibre system and determine its potential in accelerating hyperglycaemic wound healing. Methods: The effective dose of Ecklonia cava phlorotannins (ECP) for hyperglycaemic wound healing was determined prior to phlorotannin nanofibre fabrication using polyvinyl-alcohol (PVA), polyvinylpyrrolidone (PVP), and ECP. Vapour glutaraldehyde was used for crosslinking of the PVA/PVP nanofibres. The phlorotannin nanofibres were characterised, and their safety and cytocompatibility were validated. Next, the wound healing effect of phlorotannin nanofibres was determined with 2D wound scratch assay, whereas immunofluorescence staining of Collagen-I (Col-I) and Cytokeratin-14 (CK-14) was performed in human dermal fibroblasts (HDF) and human epidermal keratinocytes (HEK), respectively. Results: Our results demonstrated that 0.01 μg/mL ECP significantly improved hyperglycaemic wound healing without compromising cell viability and proliferation. Among all nanofibres, PVA/PVP/0.01 wt% ECP nanofibres exhibited the best hyperglycaemic wound healing effect. They displayed a diameter of 334.7 ± 10.1 nm, a porosity of 40.7 ± 3.3%, and a WVTR of 1718.1 ± 32.3 g/m2/day. Besides, the FTIR spectra and phlorotannin release profile validated the successful vapour glutaraldehyde crosslinking and ECP incorporation. We also demonstrated the potential of phlorotannin nanofibres as a non-cytotoxic wound dressing as they support the viability and proliferation of both HDF and HEK. Furthermore, phlorotannin nanofibres significantly ameliorated the impaired hyperglycaemic wound healing and restored the hyperglycaemic-induced Col-I reduction in HDF. Conclusion: Taken together, our findings show that phlorotannin nanofibres have the potential to be used as a diabetic wound dressing. Background: Diabetic foot ulcer (DFU) is a major debilitating complication of diabetes. The lack of effective diabetic wound dressings has been a significant problem in DFU management. In this study, we aim to establish a phlorotannin-incorporated nanofibre system and determine its potential in accelerating hyperglycaemic wound healing. Methods: The effective dose of Ecklonia cava phlorotannins (ECP) for hyperglycaemic wound healing was determined prior to phlorotannin nanofibre fabrication using polyvinyl-alcohol (PVA), polyvinylpyrrolidone (PVP), and ECP. Vapour glutaraldehyde was used for crosslinking of the PVA/PVP nanofibres. The phlorotannin nanofibres were characterised, and their safety and cytocompatibility were validated. Next, the wound healing effect of phlorotannin nanofibres was determined with 2D wound scratch assay, whereas immunofluorescence staining of Collagen-I (Col-I) and Cytokeratin-14 (CK-14) was performed in human dermal fibroblasts (HDF) and human epidermal keratinocytes (HEK), respectively. Results: Our results demonstrated that 0.01 μg/mL ECP significantly improved hyperglycaemic wound healing without compromising cell viability and proliferation. Among all nanofibres, PVA/PVP/0.01 wt% ECP nanofibres exhibited the best hyperglycaemic wound healing effect. They displayed a diameter of 334.7 ± 10.1 nm, a porosity of 40.7 ± 3.3%, and a WVTR of 1718.1 ± 32.3 g/m2/day. Besides, the FTIR spectra and phlorotannin release profile validated the successful vapour glutaraldehyde crosslinking and ECP incorporation. We also demonstrated the potential of phlorotannin nanofibres as a non-cytotoxic wound dressing as they support the viability and proliferation of both HDF and HEK. Furthermore, phlorotannin nanofibres significantly ameliorated the impaired hyperglycaemic wound healing and restored the hyperglycaemic-induced Col-I reduction in HDF. Conclusion: Taken together, our findings show that phlorotannin nanofibres have the potential to be used as a diabetic wound dressing.

피부이식술을 통한 만성 당뇨족 창상 치료의 효용성

김윤정,김보성,정호원,안재훈 대한족부족관절학회 2022 대한족부족관절학회지 Vol.26 No.2

Purpose: The purpose of this study was to evaluate the surgical outcome of split-thickness skin graft (STSG) for chronic diabetic wounds of the foot and ankle. Materials and Methods: The medical records of 20 patients who underwent surgery for chronic diabetic wounds of the foot and ankle between October 2013 and May 2018 were reviewed. Surgical management consisted of consecutive debridement, followed by negativepressure wound therapy and STSG. We used an acellular dermal matrix between the wound and the overlying STSG in some patients with wide or uneven wounds. Patient satisfaction, comorbidities, wound size and location, length of hospital stay, wound healing time, and complications were investigated. Results: Of 20 patients, 17 (85.0%) were satisfied with the surgical outcome. Eight patients had diabetic wounds associated with peripheral vascular disease (PVD), 7 patients had diabetic wounds without PVD, and 5 patients had acute infection superimposed with necrotizing abscesses. The mean size of the wound was 49.6 cm2 . The mean length of hospital stay was 33.3 days. The mean time to wound healing was 7.9 weeks. The mean follow-up period was 25.9 months. Complications included delayed wound healing (4 cases) and recurrence of the diabetic wounds (2 cases), which were resolved by meticulous wound dressing. Conclusion: STSG remains a good treatment strategy for chronic diabetic wounds of the foot and ankle.

Effect of Hominis Placenta on cutaneous wound healing in normal and diabetic mice

Ji-Yeun Park,Jiyoung Lee,Minsu Jeong,Seorim Min,Song-Yi Kim,Hyejung Lee,Yunsook Lim,Hi-Joon Park 한국영양학회 2014 Nutrition Research and Practice Vol.8 No.4

BACKGROUND/OBJECTIVES: The number of diabetic patients has recently shown a rapid increase, and delayed wound healing is a major clinical complication in diabetes. In this study, the wound healing effect of Hominis placenta (HP) treatment was investigated in normal and streptozotocin-induced diabetic mice. MATERIALS/METHODS: Four full thickness wounds were created using a 4 mm biopsy punch on the dorsum. HP was injected subcutaneously at the middle region of the upper and lower wounds. Wounds were digitally photographed and wound size was measured every other day until the 14th day. Wound closure rate was analyzed using CANVAS 7SE software. Wound tissues were collected on days 2, 6, and 14 after wounding for H/E, immunohistochemistry for FGF2, and Masson"s trichrome staining for collagen study. RESULTS: Significantly faster wound closure rates were observed in the HP treated group than in normal and diabetes control mice on days 6 and 8. Treatment with HP resulted in reduced localization of inflammatory cells in wounded skin at day 6 in normal mice and at day 14 in diabetic mice (P < 0.01). Expression of fibroblast growth factor (FGF) 2 showed a significant increase in the HP treated group on day 14 in both normal (P < 0.01) and diabetic mice (P < 0.05). In addition, HP treated groups showed a thicker collagen layer than no treatment groups, which was remarkable on the last day, day 14, in both normal and diabetic mice. CONCLUSIONS: Taken together, HP treatment has a beneficial effect on acceleration of cutaneous wound healing via regulation of the entire wound healing process, including inflammation, proliferation, and remodeling.

P024 : Autologous and allogeneic fibroblasts transplantation study in the diabetic mouse ulcer healing

( Gyong Moon Kim ),( Han Mi Jung ),( Ju Hee Lee ),( En Ah Cho ),( Young Min Park ) 대한피부과학회 2013 대한피부과학회 학술발표대회집 Vol.65 No.2

Background: The concept of induced pluripotent stem cells ( IPS) might suggest that genetically programmed or modified somatic cells such as IPS from somatic cells or somatic cells themselves as lipocytes, fibroblasts could be another source of cell therapy, especially in the poor diabetic wound healing. Objectives: The aim of this study was to evaluate the effectiveness about the autologous fibroblasts of diabetic mouse themselves as a alternatives of complex stem cell transplantation therapy. Methods: We chose diabetic wound model as a chronic nonhealing wound. We sampled and cultured dermal fibroblasts from each diabetic mouse. After 3rd passage of cell culture, each pellet of fibroblasts cultured autologously was transplanted into each wound of diabetic mouse themselves. Results: Wound healing of autologous diabetic dermal fibroblast-transplanted group showed better wound healing than that of allogeneic normal fibroblast-transplanted group. Induced diabetic dermal tissues showed similar growth factor activity with previously normal conditions. Immunohistochemical and real-time PCR about TGF-β and VEGF also showed better wound healing for the autologous wound group than that of the allogeneic normal fibroblasts cell transplanted group with statistical significance. Conclusion: Autologously cultured and transplanted wounds were seemed to show better healing in clinical, histochemical, immunohistochemical (TGF-beta, VEGF) and quantitative assays (TGF-beta, VEGF for the RT-PCR). Furthermore, diabetic fibroblasts can be expected to show similar effectiveness with normal conditions.

Polydeoxyribonucleotides Improve Diabetic Wound Healing in Mouse Animal Model for Experimental Validation

권태린,한성원,김종환,이병철,김재민,홍지연,김범준 대한피부과학회 2019 Annals of Dermatology Vol.31 No.4

Background: Wound healing mechanisms is believed to have effects similar to wound healing disorders in diabetic patients, including abnormal inflammatory cells, angiogenesis disorders, and reduced collagen synthesis. Therefore, reestablishment of structural and promoted angiogenesis could be beneficial to promote wound healing process. Objective: Therefore, we investigated whether the polydeoxyribonucleotide (PDRN) that was self-production in Korea, could be useful as an intradermal injection for promoting wound healing. Also, we validate for wound healing effect of PDRN using healing-impaired (db/db) mice. Methods: In this study, we confirmed the effects of PDRN by creating wound models in in vitro and in vivo model. Using an in vitro wound healing assay, we observed that PDRN stimulated closure of wounded monolayers of human fibroblast cells. PDRN (8.25 mg/ml) or phosphate-buffered saline (0.9% NaCl) was injected once daily into the dermis adjacent to the wound for 12 days after skin injury. Results: Time course observations revealed that mice treated with PDRN showed accelerated wound closure and epidermal and dermal regeneration, enhanced angiogenesis. The wound area and depth decreased at 3, 6, 9, and 12 days after skin injury. Histological evaluation showed an increase of vascular endothelial growth factor, CD31, and collagen fibers in the PDRN group compared with the control group, indicating that PDRN was effective in the treatment of delayed wound healing caused by diabetes. Conclusion: This study suggests that our PDRN has a wound healing effect in transgenic animal models with cells and diabetes through angiogenesis.

Polydeoxyribonucleotides Improve Diabetic Wound Healing in Mouse Animal Model for Experimental Validation

( Tae-rin Kwon ),( Sung Won Han ),( Jong Hwan Kim ),( Byung Chul Lee ),( Jae Min Kim ),( Ji Yeon Hong ),( Beom Joon Kim ) 대한피부과학회 2019 Annals of Dermatology Vol.31 No.4

Background: Wound healing mechanisms is believed to have effects similar to wound healing disorders in diabetic patients, including abnormal inflammatory cells, angiogenesis disorders, and reduced collagen synthesis. Therefore, reestablishment of structural and promoted angiogenesis could be beneficial to promote wound healing process. Objective: Therefore, we investigated whether the polydeoxyribonucleotide (PDRN) that was self-production in Korea, could be useful as an intradermal injection for promoting wound healing. Also, we validate for wound healing effect of PDRN using healing-impaired (db/db) mice. Methods: In this study, we confirmed the effects of PDRN by creating wound models in in vitro and in vivo model. Using an in vitro wound healing assay, we observed that PDRN stimulated closure of wounded monolayers of human fibroblast cells. PDRN (8.25 mg/ml) or phosphate-buffered saline (0.9% NaCl) was injected once daily into the dermis adjacent to the wound for 12 days after skin injury. Results: Time course observations revealed that mice treated with PDRN showed accelerated wound closure and epidermal and dermal regeneration, enhanced angiogenesis. The wound area and depth decreased at 3, 6, 9, and 12 days after skin injury. Histological evaluation showed an increase of vascular endothelial growth factor, CD31, and collagen fibers in the PDRN group compared with the control group, indicating that PDRN was effective in the treatment of delayed wound healing caused by diabetes. Conclusion: This study suggests that our PDRN has a wound healing effect in transgenic animal models with cells and diabetes through angiogenesis. (Ann Dermatol 31(4) 403∼413, 2019)

Therapeutic Effects of Amnion-Conjugated Chitosan-Alginate Membranes on Diabetic Wounds in an Induced Diabetic Swine Model: An In Vitro and In Vivo Study

Jeong Woonhyeok,Hong Jamin,Jung Minho,Jang Mijin,An Sanghyun,Jo Taehee,Kwon Sunyoung,손대구 대한성형외과학회 2022 Archives of Plastic Surgery Vol.49 No.2

Background Chitosan (CS) is a well-known antimicrobial dressing material. Moreover, widely used amniotic membranes contain growth factors beneficial for wound healing. Herein, we created a novel amnion-conjugated CS-alginate membrane dressing and tested its wound healing potency in a diabetic swine model.Methods The bovine amniotic powder growth factor contents were evaluated by protein assay, and the powder's wound healing effects were assessed in vitro by HaCaT cell scratch closure. In vivo, two minipigs developed streptozotocin-induced diabetes. Serial serum glucose measurements and intravenous glucose tolerance tests were performed to confirm their diabetic status. Twelve square-shaped wounds created on each pig's back were randomly divided into control (n = 4), CS (n = 4), and amnion-CS (AC; n = 4) groups and treated accordingly with different dressings. Wound healing in each group was assessed by measuring wound contraction over time, capturing wound perfusion with indocyanine green (ICG) angiography, and histologically analyzing inflammatory markers.Results Amniotic powder elution promoted HaCaT cell migration in the scratch wound model, suggesting its beneficial in vitro wound healing effects. In vivo, the CS and AC groups showed earlier wound contraction initiation and reepithelialization and earlier wound perfusion improvement by ICG angiography than the control group. Additionally, the wound size of the AC group at week 3 was significantly smaller than those in the control group. There was no significant difference in the numbers of acute and chronic inflammatory cells between the groups.Conclusion The amnion-conjugated CS-alginate membrane, as well as CS dressing alone, could be a favorable dressing option for diabetic wounds.

혈액은행의 혈소판농축액을 이용한 당뇨생쥐의 창상치유

한승규,정성호,이병일,김우경,Finn Gottrup 대한성형외과학회 2007 Archives of Plastic Surgery Vol.34 No.3

Purpose: Many clinical trials have shown the effectiveness of platelet releasate on chronic wounds. However, a large volume of blood must be aspirated from a patient and a platelet separator is required. Here, we hypothesized that platelet concentrate obtained from a blood bank (PCBB) would be also effective at stimulating wound healing. The purpose of this study was to investigate the effectiveness of PCBB on accelerating healing of diabetic wounds in vivo.Methods: Round wounds of 5mm diameter were made at four sites(two wounds on the left and two on the right side) on the backs of nine diabetic mice. Three hundred million platelets suspended in 0.05ml fibrinogen were dispersed on each wound on left sides. Same amount of fibrinogen without platelets was dispersed on right side control wounds. Thereafter, 0.05ml thrombin was applied to the each wound. Ten days after wound treatment, healed wounds were excised and the extent of wound healing in each group was compared. Results: Quantitative histologic analysis of epithelial gap distances revealed that PCBB treatment had greatly accelerated wound healing. Mean epithelial gap distances for PCBB treated and control wounds were 2.5 ×0.6mm and 3.6×0.5mm, respectively(p<0.05). Conclusion: Our results suggest that PCBB has potential to accelerate the healing of diabetic wounds.