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1
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Yilmaz EG, Hacıosmanoğlu N, Jordi SBU, Yilmaz B, Inci F. Revolutionizing IBD research with on-chip models of disease modeling and drug screening. Trends Biotechnol 2025; 43:1062-1078. [PMID: 39523166 DOI: 10.1016/j.tibtech.2024.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 08/30/2024] [Accepted: 10/03/2024] [Indexed: 11/16/2024]
Abstract
Inflammatory bowel disease (IBD) comprises chronic inflammatory conditions with complex mechanisms and diverse manifestations, posing significant clinical challenges. Traditional animal models and ethical concerns in human studies necessitate innovative approaches. This review provides an overview of human intestinal architecture in health and inflammation, emphasizing the role of microfluidics and on-chip technologies in IBD research. These technologies allow precise manipulation of cellular and microbial interactions in a physiologically relevant context, simulating the intestinal ecosystem microscopically. By integrating cellular components and replicating 3D tissue architecture, they offer promising models for studying host-microbe interactions, wound healing, and therapeutic approaches. Continuous refinement of these technologies promises to advance IBD understanding and therapy development, inspiring further innovation and cross-disciplinary collaboration.
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Affiliation(s)
- Eylul Gulsen Yilmaz
- UNAM-National Nanotechnology Research Center, Bilkent University, 06800 Ankara, Turkey; Institute of Materials Science and Nanotechnology, Bilkent University, 06800 Ankara, Turkey
| | - Nedim Hacıosmanoğlu
- UNAM-National Nanotechnology Research Center, Bilkent University, 06800 Ankara, Turkey; Institute of Materials Science and Nanotechnology, Bilkent University, 06800 Ankara, Turkey
| | - Sebastian Bruno Ulrich Jordi
- Department of Visceral Surgery and Medicine, Bern University Hospital, University of Bern, 3010, Bern, Switzerland; Maurice Müller Laboratories, Department for Biomedical Research, University of Bern, 3008, Bern, Switzerland
| | - Bahtiyar Yilmaz
- Department of Visceral Surgery and Medicine, Bern University Hospital, University of Bern, 3010, Bern, Switzerland; Maurice Müller Laboratories, Department for Biomedical Research, University of Bern, 3008, Bern, Switzerland.
| | - Fatih Inci
- UNAM-National Nanotechnology Research Center, Bilkent University, 06800 Ankara, Turkey; Institute of Materials Science and Nanotechnology, Bilkent University, 06800 Ankara, Turkey.
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2
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Cariba S, Srivastava A, Bronsema K, Kouthouridis S, Zhang B, Payne SL. Innervated Coculture Device to Model Peripheral Nerve-Mediated Fibroblast Activation. ACS Biomater Sci Eng 2024; 10:7566-7576. [PMID: 39601321 PMCID: PMC11633653 DOI: 10.1021/acsbiomaterials.4c01482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 11/06/2024] [Accepted: 11/20/2024] [Indexed: 11/29/2024]
Abstract
Cutaneous wound healing is a complex process involving various cellular and molecular interactions, resulting in the formation of a collagen-rich scar with imperfect function and morphology. Dermal fibroblasts are crucial to successful wound healing, migrating to the wound site where they are activated to provide extracellular matrix remodeling and wound closure. Peripheral nerves have been shown to play an important role in wound healing, with loss or damage to these nerves often leading to impaired healing and the formation of chronic nonhealing wounds. Previous research has suggested that sensory nerves secrete trophic factors that can regulate wound healing, including fibroblast activation; however, the direct cell-cell interaction between nerves and fibroblasts has not been extensively studied. To address this knowledge gap, we developed an in vitro co-culture model using a device called the IFlowPlate. This model supports the long-term viability of multiple cell types while allowing for direct contact between sensory nerve cells and dermal fibroblasts. Using the IFlowPlate, we demonstrate that co-culture of dorsal root ganglia with dermal fibroblasts increases fibroblast proliferation, collagen and α-smooth muscle actin expression, and secretion of pro-wound healing factors, suggesting that nerves can promote wound healing by modulating fibroblast activation. The IFlowPlate offers a user-friendly and high-throughput platform to study the in vitro interactions between nerves and a variety of cell types that can be applied to wound healing and other important biological processes.
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Affiliation(s)
- Solsa Cariba
- Department
of Biomedical Sciences, University of Guelph, Guelph N1G 2W1, Canada
| | - Avika Srivastava
- Department
of Biomedical Sciences, University of Guelph, Guelph N1G 2W1, Canada
| | - Kendra Bronsema
- Department
of Biomedical Sciences, University of Guelph, Guelph N1G 2W1, Canada
| | - Sonya Kouthouridis
- Department
of Chemical Engineering, McMaster University, Hamilton L8S 4L8, Canada
| | - Boyang Zhang
- Department
of Chemical Engineering, McMaster University, Hamilton L8S 4L8, Canada
- School
of Biomedical Engineering, McMaster University, Hamilton L8S 4L8, Canada
| | - Samantha L. Payne
- Department
of Biomedical Sciences, University of Guelph, Guelph N1G 2W1, Canada
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Liu X, Teng Y, Li H, Luo D, Li H, Shen J, Du S, Zhang Y, Wang D, Jing J. Identification of IGF2 promotes skin wound healing by co-expression analysis. Int Wound J 2024; 21:e14862. [PMID: 38572823 PMCID: PMC10993366 DOI: 10.1111/iwj.14862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Revised: 03/15/2024] [Accepted: 03/18/2024] [Indexed: 04/05/2024] Open
Abstract
Oral mucosa is an ideal model for studying scarless wound healing. Researchers have shown that the key factors which promote scarless wound healing already exist in basal state of oral mucosa. Thus, to identify the other potential factors in basal state of oral mucosa will benefit to skin wound healing. In this study, we identified eight gene modules enriched in wound healing stages of human skin and oral mucosa through co-expression analysis, among which the module M8 was only module enriched in basal state of oral mucosa, indicating that the genes in module M8 may have key factors mediating scarless wound healing. Through bioinformatic analysis of genes in module M8, we found IGF2 may be the key factor mediating scarless wound healing of oral mucosa. Then, we purified IGF2 protein by prokaryotic expression, and we found that IGF2 could promote the proliferation and migration of HaCaT cells. Moreover, IGF2 promoted wound re-epithelialization and accelerated wound healing in a full-thickness skin wound model. Our findings identified IGF2 as a factor to promote skin wound healing which provide a potential target for wound healing therapy in clinic.
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Affiliation(s)
- Xingyan Liu
- School and Hospital of Stomatology, Zunyi Medical UniversityZunyiChina
- Department of Burns and Plastic SurgeryAffiliated Hospital of Zunyi Medical UniversityZunyiChina
- The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical UniversityZunyiChina
| | - Ying Teng
- School and Hospital of Stomatology, Zunyi Medical UniversityZunyiChina
- Department of Burns and Plastic SurgeryAffiliated Hospital of Zunyi Medical UniversityZunyiChina
- The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical UniversityZunyiChina
| | - Huan Li
- School and Hospital of Stomatology, Zunyi Medical UniversityZunyiChina
| | - Ding Luo
- School and Hospital of Stomatology, Zunyi Medical UniversityZunyiChina
| | - Hongkun Li
- School and Hospital of Stomatology, Zunyi Medical UniversityZunyiChina
- Department of Burns and Plastic SurgeryAffiliated Hospital of Zunyi Medical UniversityZunyiChina
- The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical UniversityZunyiChina
| | - Jinghan Shen
- School and Hospital of Stomatology, Zunyi Medical UniversityZunyiChina
- Department of Burns and Plastic SurgeryAffiliated Hospital of Zunyi Medical UniversityZunyiChina
- The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical UniversityZunyiChina
| | - Simin Du
- School and Hospital of Stomatology, Zunyi Medical UniversityZunyiChina
- Department of Burns and Plastic SurgeryAffiliated Hospital of Zunyi Medical UniversityZunyiChina
- The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical UniversityZunyiChina
| | - Yuyue Zhang
- School and Hospital of Stomatology, Zunyi Medical UniversityZunyiChina
- Department of Burns and Plastic SurgeryAffiliated Hospital of Zunyi Medical UniversityZunyiChina
- The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical UniversityZunyiChina
| | - Dali Wang
- Department of Burns and Plastic SurgeryAffiliated Hospital of Zunyi Medical UniversityZunyiChina
- The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical UniversityZunyiChina
| | - Jie Jing
- School and Hospital of Stomatology, Zunyi Medical UniversityZunyiChina
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PARSPANCI A, KEÇECİ Y, TEMİZ P. The effect of human recombinant epidermal growth factor on neovascularization and pedicle division time in a rat interpolation flap model. Turk J Med Sci 2024; 54:471-482. [PMID: 39050389 PMCID: PMC11265903 DOI: 10.55730/1300-0144.5812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 04/04/2024] [Accepted: 01/05/2024] [Indexed: 07/27/2024] Open
Abstract
Background/aim In practice, waiting 2-3 weeks for interpolation flaps pedicle division result in certain morbidities and discomfort for patient. The division time of flap pedicle depends on neovascularization from the recipient bed and includes wound healing stages. We aimed to investigate the effect of recombinant human epidermal growth factor (rhEGF) on the flap viability during early pedicle division. Materials and methods Thirty-six rats were allocated to two main groups as control and study. A cranial based flap measuring 5 × 5 cm was elevated from the back, including all layers of the skin. While the cranial half of the defect was primarily closed, the flap was inset into the distal half. In the study group, a single dose of 20 μg EGF was injected into the recipient site and wound edges before the flap inset. The control group received no treatment. Each main group was divided into three subgroups based on pedicle division time of 8, 11 and 14 days. After pedicle division, each flap was monitored and photographed for 7 days, and histopathological samples were collected. Viable and necrotic areas were compared, and flaps were examined histopathologically. Results The necrosis area in the study group on the 11th day was significantly lower than that in the control group. The fibroblastic activity, granulation tissue and neovascularization on the 8th day, the granulation tissue level on the 11th day, and the neovascularization level on the 14th day were significantly higher in the study groups. Conclusion Following the application of EGF, the necrosis area decreased within the study group. Histopathological assessments revealed a statistically significant increase in parameters related to granulation tissue and fibroblastic activity, notably neovascularization, across all subgroups within the study. It was concluded that the use of EGF positively affected the neovascularization, and flaps could be divided earlier.
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Affiliation(s)
- Aziz PARSPANCI
- Department of Plastic, Reconstructive and Aesthetic Surgery, Bayburt State Hospital, Bayburt,
Turkiye
| | - Yavuz KEÇECİ
- Department of Plastic, Reconstructive and Aesthetic Surgery, Manisa Celal Bayar University, Manisa,
Turkiye
| | - Peyker TEMİZ
- Department of Pathology, Manisa Celal Bayar University, Manisa,
Turkiye
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Radzikowska-Büchner E, Łopuszyńska I, Flieger W, Tobiasz M, Maciejewski R, Flieger J. An Overview of Recent Developments in the Management of Burn Injuries. Int J Mol Sci 2023; 24:16357. [PMID: 38003548 PMCID: PMC10671630 DOI: 10.3390/ijms242216357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 11/09/2023] [Accepted: 11/13/2023] [Indexed: 11/26/2023] Open
Abstract
According to the World Health Organization (WHO), around 11 million people suffer from burns every year, and 180,000 die from them. A burn is a condition in which heat, chemical substances, an electrical current or other factors cause tissue damage. Burns mainly affect the skin, but can also affect deeper tissues such as bones or muscles. When burned, the skin loses its main functions, such as protection from the external environment, pathogens, evaporation and heat loss. Depending on the stage of the burn, the patient's condition and the cause of the burn, we need to choose the most appropriate treatment. Personalization and multidisciplinary collaboration are key to the successful management of burn patients. In this comprehensive review, we have collected and discussed the available treatment options, focusing on recent advances in topical treatments, wound cleansing, dressings, skin grafting, nutrition, pain and scar tissue management.
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Affiliation(s)
- Elżbieta Radzikowska-Büchner
- Department of Plastic, Reconstructive and Maxillary Surgery, National Medical Institute of the Ministry of the Interior and Administration, Wołoska 137 Street, 02-507 Warszawa, Poland;
| | - Inga Łopuszyńska
- Department of Plastic, Reconstructive and Maxillary Surgery, National Medical Institute of the Ministry of the Interior and Administration, Wołoska 137 Street, 02-507 Warszawa, Poland;
| | - Wojciech Flieger
- Department of Human Anatomy, Medical University of Lublin, Jaczewskiego 4 Street, 20-090 Lublin, Poland;
| | - Michał Tobiasz
- Department of Plastic Surgery, Reconstructive Surgery and Burn Treatment, Medical University of Lublin, Krasnystawska 52 Street, 21-010 Łęczna, Poland;
| | - Ryszard Maciejewski
- Faculty of Medicine, University of Warsaw, Żwirki i Wigury 101 Street, 02-089 Warszawa, Poland;
| | - Jolanta Flieger
- Department of Analytical Chemistry, Medical University of Lublin, Chodźki 4A Street, 20-093 Lublin, Poland
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Lee Y, Lim S, Kim JA, Chun YH, Lee HJ. Development of Thiol-Ene Reaction-Based HA Hydrogel with Sustained Release of EGF for Enhanced Skin Wound Healing. Biomacromolecules 2023; 24:5342-5352. [PMID: 37734002 DOI: 10.1021/acs.biomac.3c00810] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/23/2023]
Abstract
This study develops a novel drug delivery system using a hyaluronic acid (HA) hydrogel for controlled release of epidermal growth factor (EGF) to enhance skin wound healing. Conventional hydrogel-based methods suffer from a burst release and limited drug delivery times. To address this, we employ bioconjugation to introduce an acrylate group to EGF, enabling chemical bonding to the HA hydrogel matrix through thiol-ene cross-linking. This approach results in sustained-release delivery of EGF based on the degradation rate of the HA matrix, overcoming diffusion-based limitations. We confirm the introduction of the acrylate group using matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. We evaluated the hydrogel morphology and rheological properties following binding of acrylate-conjugated EGF to the HA matrix. Assessment of the EGF release profile demonstrates delayed release compared to unconjugated EGF. We evaluate the impact on cells through cell proliferation and scratch assays, indicating the system's efficacy. In a rat wound healing model, the sustained release of EGF from the hydrogel system promotes appropriate tissue healing and restores it to a normal state. These findings suggest that this practical drug delivery system, involving the modification of growth factors or drugs to chemically bind healing factors to hydrogels, can achieve long-lasting effects.
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Affiliation(s)
- Yerin Lee
- Department of Chemical and Biological Engineering, Gachon University, 1342 Seongnam-daero, Seongnam-si, Gyeonggi-do 13120, Republic of Korea
| | - Saebin Lim
- Department of Chemical and Biological Engineering, Gachon University, 1342 Seongnam-daero, Seongnam-si, Gyeonggi-do 13120, Republic of Korea
| | - Ji An Kim
- Department of Pediatrics, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon 21431, Republic of Korea
| | - Yoon Hong Chun
- Department of Pediatrics, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon 21431, Republic of Korea
| | - Hyun Jong Lee
- Department of Chemical and Biological Engineering, Gachon University, 1342 Seongnam-daero, Seongnam-si, Gyeonggi-do 13120, Republic of Korea
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Ali M, Kwak SH, Byeon JY, Choi HJ. In Vitro and In Vivo Evaluation of Epidermal Growth Factor (EGF) Loaded Alginate-Hyaluronic Acid (AlgHA) Microbeads System for Wound Healing. J Funct Biomater 2023; 14:403. [PMID: 37623648 PMCID: PMC10455903 DOI: 10.3390/jfb14080403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/11/2023] [Accepted: 07/25/2023] [Indexed: 08/26/2023] Open
Abstract
The management of skin injuries is one of the most common concerns in medical facilities. Different types of biomaterials with effective wound-healing characteristics have been studied previously. In this study, we used alginate (Alg) and hyaluronic acid (HA) composite (80:20) beads for the sustained release of epidermal growth factor (EGF) delivery. Heparin crosslinked AlgHA beads showed significant loading and entrapment of EGF. Encapsulated beads demonstrated biocompatibility with rat L929 cells and significant migration at the concentration of AlgHAEGF100 and AlgHAEGF150 within 24 h. Both groups significantly improved the expression of Fetal Liver Kinase 1 (FLK-1) along with the Intercellular Adhesion Molecule-1 (ICAM-1) protein in rat bone Mesenchymal stem cells (rbMSCs). In vivo assessment exhibited significant epithelialization and wound closure gaps within 2 weeks. Immunohistochemistry shows markedly significant levels of ICAM-1, FLK-1, and fibronectin (FN) in the AlgHAEGF100 and AlgHAEGF150 groups. Hence, we conclude that the EGF-loaded alginate-hyaluronic acid (AlgHA) bead system can be used to promote wound healing.
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Affiliation(s)
- Maqsood Ali
- Department of Regenerative Medicine, College of Medicine, Soonchunhyang University, Cheonan 31538, Republic of Korea
| | - Si Hyun Kwak
- Department of Plastic and Reconstructive Surgery, College of Medicine, Soonchunhyang University, Cheonan 31538, Republic of Korea
| | - Je Yeon Byeon
- Department of Plastic and Reconstructive Surgery, College of Medicine, Soonchunhyang University, Cheonan 31538, Republic of Korea
| | - Hwan Jun Choi
- Department of Plastic and Reconstructive Surgery, College of Medicine, Soonchunhyang University, Cheonan 31538, Republic of Korea
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Zheng SY, Wan XX, Kambey PA, Luo Y, Hu XM, Liu YF, Shan JQ, Chen YW, Xiong K. Therapeutic role of growth factors in treating diabetic wound. World J Diabetes 2023; 14:364-395. [PMID: 37122434 PMCID: PMC10130901 DOI: 10.4239/wjd.v14.i4.364] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/16/2023] [Accepted: 03/21/2023] [Indexed: 04/12/2023] Open
Abstract
Wounds in diabetic patients, especially diabetic foot ulcers, are more difficult to heal compared with normal wounds and can easily deteriorate, leading to amputation. Common treatments cannot heal diabetic wounds or control their many complications. Growth factors are found to play important roles in regulating complex diabetic wound healing. Different growth factors such as transforming growth factor beta 1, insulin-like growth factor, and vascular endothelial growth factor play different roles in diabetic wound healing. This implies that a therapeutic modality modulating different growth factors to suit wound healing can significantly improve the treatment of diabetic wounds. Further, some current treatments have been shown to promote the healing of diabetic wounds by modulating specific growth factors. The purpose of this study was to discuss the role played by each growth factor in therapeutic approaches so as to stimulate further therapeutic thinking.
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Affiliation(s)
- Shen-Yuan Zheng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, Hunan Province, China
| | - Xin-Xing Wan
- Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
| | - Piniel Alphayo Kambey
- Department of Neurobiology and Anatomy, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China
| | - Yan Luo
- Clinical Medicine Eight-Year Program, Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China
| | - Xi-Min Hu
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, Hunan Province, China
| | - Yi-Fan Liu
- Clinical Medicine Eight-Year Program, Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China
| | - Jia-Qi Shan
- Clinical Medicine Eight-Year Program, Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China
| | - Yu-Wei Chen
- Clinical Medicine Eight-Year Program, Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China
| | - Kun Xiong
- Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, Hunan Province, China
- Key Laboratory of Emergency and Trauma, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, Hainan Province, China
- Hunan Key Laboratory of Ophthalmology, Central South University, Changsha 410013, Hunan Province, China
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Ratanapokasatit Y, Sirithanabadeekul P. The Efficacy and Safety of Epidermal Growth Factor Combined with Fractional Carbon Dioxide Laser for Acne Scar Treatment: A Split-Face Trial. THE JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY 2022; 15:44-48. [PMID: 35942017 PMCID: PMC9345195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
BACKGROUND Epidermal growth factor (EGF) stimulates collagen production and supports the wound healing process. However, there are no studies on fractional carbon dioxide (CO2) laser combined with EGF for acne scar treatment. OBJECTIVE We sought to evaluate the efficacy and safety of fractional CO2 laser combined with topical EGF versus fractional CO2 laser alone in the treatment of acne scars. METHODS Twenty-three patients with atrophic acne scars underwent three monthly sessions of randomized split-face application of fractional CO2 laser combined with topical EGF or placebo twice daily for seven days following each laser session. Scar improvement was evaluated at one month and three months posttreatment by two blinded dermatologists and the Antera 3D® skin analysis system. Wound healing response and adverse events were also evaluated. RESULTS Twenty-one patients completed the trial. According to dermatologist grading and skin analysis system, EGF showed significant superiority at three months posttreatment compared to placebo. The wound healing response did not differ between the groups. Surprisingly, the melanin index on the EGF side showed a significant decrease at three months posttreatment, compared to placebo. There was no allergic reaction to the topical EGF. CONCLUSION Treatment with topical EGF after ablative fractional CO2 laser improves the clinical appearance of atrophic acne scars, and EGF may help decrease skin pigmentation after laser treatment. The use of topical EGF is safe when applied to post-laser ablation.
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Affiliation(s)
- Yanisa Ratanapokasatit
- Both authors are with the Department of Dermatology, Chulabhorn International College of Medicine at Thammasat University in Pathum Thani, Thailand
| | - Punyaphat Sirithanabadeekul
- Both authors are with the Department of Dermatology, Chulabhorn International College of Medicine at Thammasat University in Pathum Thani, Thailand
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Kaur G, Narayanan G, Garg D, Sachdev A, Matai I. Biomaterials-Based Regenerative Strategies for Skin Tissue Wound Healing. ACS APPLIED BIO MATERIALS 2022; 5:2069-2106. [PMID: 35451829 DOI: 10.1021/acsabm.2c00035] [Citation(s) in RCA: 66] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Skin tissue wound healing proceeds through four major stages, including hematoma formation, inflammation, and neo-tissue formation, and culminates with tissue remodeling. These four steps significantly overlap with each other and are aided by various factors such as cells, cytokines (both anti- and pro-inflammatory), and growth factors that aid in the neo-tissue formation. In all these stages, advanced biomaterials provide several functional advantages, such as removing wound exudates, providing cover, transporting oxygen to the wound site, and preventing infection from microbes. In addition, advanced biomaterials serve as vehicles to carry proteins/drug molecules/growth factors and/or antimicrobial agents to the target wound site. In this review, we report recent advancements in biomaterials-based regenerative strategies that augment the skin tissue wound healing process. In conjunction with other medical sciences, designing nanoengineered biomaterials is gaining significant attention for providing numerous functionalities to trigger wound repair. In this regard, we highlight the advent of nanomaterial-based constructs for wound healing, especially those that are being evaluated in clinical settings. Herein, we also emphasize the competence and versatility of the three-dimensional (3D) bioprinting technique for advanced wound management. Finally, we discuss the challenges and clinical perspective of various biomaterial-based wound dressings, along with prospective future directions. With regenerative strategies that utilize a cocktail of cell sources, antimicrobial agents, drugs, and/or growth factors, it is expected that significant patient-specific strategies will be developed in the near future, resulting in complete wound healing with no scar tissue formation.
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Affiliation(s)
- Gurvinder Kaur
- Materials Science and Sensor Applications, Central Scientific Instruments Organization, Chandigarh 160030, India
| | - Ganesh Narayanan
- Fiber and Polymer Science Program, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Deepa Garg
- Materials Science and Sensor Applications, Central Scientific Instruments Organization, Chandigarh 160030, India
| | - Abhay Sachdev
- Materials Science and Sensor Applications, Central Scientific Instruments Organization, Chandigarh 160030, India
| | - Ishita Matai
- Department of Biotechnology, School of Biological Sciences, Amity University Punjab, Mohali 140306, India
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11
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Sari NMA, Saputro ID, Hutagalung MR. Vascular Endothelial Growth Factor, Epidermal Growth Factor, and Epithelialization Analysis on Full-Thickness Wound Applied with Topical Erythropoietin. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.8476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND: Skin wounds are a major challenge, such as full-thickness wounds that need a long time to heal. However, the addition of erythropoietin can accelerate the wound healing process.
AIM: This study was aimed to determine the effect of topical erythropoietin administration on vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and epithelialization in the wound healing process.
METHODS: This was randomized controlled trial. Full-thickness wounds were created on the back of each white rat. No treatment was administered in the control group (n=16), and topical erythropoietin was applied in the treatment group (n=16). The rats were euthanized on day 3 and day 6 post-surgery, respectively. The expression levels of VEGF, EGF, and microscopic epithelialization rate were examined.
RESULTS: The level of EGF expression in the treatment group increased significantly on day 3 by 2.84 times compared to the control group and on day 6 increased to 4.89 times compared to the control group (p < 0.001). The level of VEGF expression in the treatment group on day 3 increased 2.18 times compared to the control group and on day 6 increased to 2.65 times compared to the control group (p < 0.001). Meanwhile, epithelialization in the treatment group on day 3 increased 1.3 times compared to the control group and on day 6 increased up to 7.62 times compared to the control group (p < 0.001).
CONLUSION: Topical administration of erythropoietin could increase the expression of VEGF, EGF, and epithelialization in both early inflammatory and proliferative phases.
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12
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Tsai HC, Sheng C, Chang LS, Wen ZH, Ho CY, Chen CM. Chitosan-microencapsulated rhEGF in promoting wound healing. J Wound Care 2021; 30:IXi-IXxi. [PMID: 34570632 DOI: 10.12968/jowc.2021.30.sup9a.ix] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
AIMS Chitosan and epidermal growth factor (EGF) have been shown to improve wound healing. This study investigates the healing effects of a spray solution (NewEpi, JoyCom Bio-Chem Co. Ltd., Taiwan) containing recombinant human EGF (rhEGF) delivered via a newly patented technology-chitosan microencapsulated nanoparticles. METHODS On Wistar rats, two full-thickness wounds on the dorsum bilateral of the spine were created. The rats were randomised to the following treatment groups: hydrogel, wet dressing, foam, rhEGF spray and rhEGF spray+foam. Sterile dressings were applied and changed daily. A total of 2μg of rhEGF was administered in two sprays during each dressing change. All animals were euthanised on day 14. Tissue samples were taken from the wound bed, including an area of 2cm surrounding the wound margin for histological evaluations. RESULTS Wounds treated with the rhEGF spray achieved the greatest size reduction by day 14 compared with other types of conventional dressings. An overall significant difference in levels of collagen synthesis existed between groups (p<0.01). Pair-wise comparisons showed that the rhEGF spray treatment significantly promoted higher levels of mature Type I collagen than any other conventional dressings (p<0.01), whereas non-rhEGF treatments resulted in higher levels of Type III collagen. The regenerated tissue in rhEGF spray treatment groups was also in alignment with that of normal skin. Epidermis, dermis and hair follicles were easily observed in wounds treated with the rhEGF spray. CONCLUSION The major challenge of topical application of rhEGF was overcome by using a new drug delivery technology: chitosan-rhEGF nanoparticles. The positive healing effects observed in this study suggest the therapeutic potentials of this novel rhEGF topical spray solution.
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Affiliation(s)
- Hsin-Chung Tsai
- Department of Surgery, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan.,Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan
| | - Christine Sheng
- Rutgers Honors College, School of Arts and Science, Department of Cell Biology and Neuroscience, New Brunswick, New Jersey, US
| | - Le-Shin Chang
- Department of Research and Development, Joycom Biochem Co., Ltd. Kaohsiung, Taiwan
| | - Zhi-Hong Wen
- Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Ching-Yin Ho
- Department of Otolaryngology, Cheng-Hsin General Hospital, Taipei, Taiwan
| | - Chuan-Mu Chen
- Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.,Taichung Veterans General Hospital, Taichung, Taiwan.,iEGG and Animal Biotechnology Center, National Chung Hsing University, Taichung, Taiwan
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13
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Sommer K, Wiendl M, Müller TM, Heidbreder K, Voskens C, Neurath MF, Zundler S. Intestinal Mucosal Wound Healing and Barrier Integrity in IBD-Crosstalk and Trafficking of Cellular Players. Front Med (Lausanne) 2021; 8:643973. [PMID: 33834033 PMCID: PMC8021701 DOI: 10.3389/fmed.2021.643973] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Accepted: 02/24/2021] [Indexed: 12/12/2022] Open
Abstract
The intestinal epithelial barrier is carrying out two major functions: restricting the entry of potentially harmful substances while on the other hand allowing the selective passage of nutrients. Thus, an intact epithelial barrier is vital to preserve the integrity of the host and to prevent development of disease. Vice versa, an impaired intestinal epithelial barrier function is a hallmark in the development and perpetuation of inflammatory bowel disease (IBD). Besides a multitude of genetic, molecular and cellular alterations predisposing for or driving barrier dysintegrity in IBD, the appearance of intestinal mucosal wounds is a characteristic event of intestinal inflammation apparently inducing breakdown of the intestinal epithelial barrier. Upon injury, the intestinal mucosa undergoes a wound healing process counteracting this breakdown, which is controlled by complex mechanisms such as epithelial restitution, proliferation and differentiation, but also immune cells like macrophages, granulocytes and lymphocytes. Consequently, the repair of mucosal wounds is dependent on a series of events including coordinated trafficking of immune cells to dedicated sites and complex interactions among the cellular players and other mediators involved. Therefore, a better understanding of the crosstalk between epithelial and immune cells as well as cell trafficking during intestinal wound repair is necessary for the development of improved future therapies. In this review, we summarize current concepts on intestinal mucosal wound healing introducing the main cellular mediators and their interplay as well as their trafficking characteristics, before finally discussing the clinical relevance and translational approaches to therapeutically target this process in a clinical setting.
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Affiliation(s)
- Katrin Sommer
- Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Maximilian Wiendl
- Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Tanja M Müller
- Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Karin Heidbreder
- Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Caroline Voskens
- Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.,Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany
| | - Markus F Neurath
- Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.,Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany
| | - Sebastian Zundler
- Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.,Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany
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14
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An Injectable Fibrin Scaffold Rich in Growth Factors for Skin Repair. BIOMED RESEARCH INTERNATIONAL 2021; 2021:8094932. [PMID: 33628814 PMCID: PMC7884109 DOI: 10.1155/2021/8094932] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 11/18/2020] [Accepted: 01/11/2021] [Indexed: 12/21/2022]
Abstract
Platelet aggregates, such as PRP, PRF, and CGF, have been used alone or in combination with other grafting materials to enhance restoration outcomes. The process for preparing these autografting materials requires two-step centrifugation or specific centrifuges. In this study, we obtained an injectable fibrin scaffold (IFS) rich in growth factors by one-step centrifugation of whole blood from rabbits. The purpose of this study is to introduce some characteristics of IFS. This scaffold was characterized using various techniques, including Masson's trichrome staining, scanning electron microscopy, porosity measurements, and cell counting. The sustained release of growth factors, including PDGF, VEGF, TGF-β1, IGF, FGF, and EGF, was quantified using ELISA assay. The obtained IFS was tested for its effects on cell proliferation, extracellular matrix deposition, and full-thickness skin defect repair. The prepared IFS is characterized by a loose fibrin network structure with white blood cells and platelets that slowly release growth factors and can promote the healing of skin defects via the promotion of cell proliferation, collagen deposition, and tissue revascularization. In addition, its liquid properties and porous structure are conducive to its application as a therapeutic component in tissue engineering.
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15
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Rouabhia M, Park HJ, Abedin‐Do A, Douville Y, Méthot M, Zhang Z. Electrical stimulation promotes the proliferation of human keratinocytes, increases the production of keratin 5 and 14, and increases the phosphorylation of ERK1/2 and p38 MAP kinases. J Tissue Eng Regen Med 2020; 14:909-919. [DOI: 10.1002/term.3040] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Revised: 03/14/2020] [Accepted: 03/23/2020] [Indexed: 12/26/2022]
Affiliation(s)
- Mahmoud Rouabhia
- Groupe de Recherche en Écologie Buccale, Faculté de Médecine DentaireUniversité Laval Quebec Canada
| | - Hyun Jin Park
- Groupe de Recherche en Écologie Buccale, Faculté de Médecine DentaireUniversité Laval Quebec Canada
- Département de Chirurgie, Faculté de Médecine, Axe Médecine Régénératrice, Centre de Recherche du CHU de QuébecUniversité Laval Quebec Canada
| | - Atieh Abedin‐Do
- Groupe de Recherche en Écologie Buccale, Faculté de Médecine DentaireUniversité Laval Quebec Canada
- Département de Chirurgie, Faculté de Médecine, Axe Médecine Régénératrice, Centre de Recherche du CHU de QuébecUniversité Laval Quebec Canada
| | - Yvan Douville
- Département de Chirurgie, Faculté de Médecine, Axe Médecine Régénératrice, Centre de Recherche du CHU de QuébecUniversité Laval Quebec Canada
| | - Mireille Méthot
- Département de Chirurgie, Faculté de Médecine, Axe Médecine Régénératrice, Centre de Recherche du CHU de QuébecUniversité Laval Quebec Canada
| | - Ze Zhang
- Département de Chirurgie, Faculté de Médecine, Axe Médecine Régénératrice, Centre de Recherche du CHU de QuébecUniversité Laval Quebec Canada
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16
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Kaya O, Orhan E, Sapmaz-Metin M, Topçu-Tarladaçalışır Y, Gündüz Ö, Aydın B. The effects of epidermal growth factor on early burn-wound progression in rats. Dermatol Ther 2019; 33:e13196. [PMID: 31849151 DOI: 10.1111/dth.13196] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 11/01/2019] [Accepted: 12/15/2019] [Indexed: 12/13/2022]
Abstract
After burns, protecting tissues by medicines in the zone of stasis reduces the width and depth of injury. This study's goal was to reduce burned tissue damage in the zone of stasis using epidermal growth factor (EGF). Forty-eight Wistar rats were separated into three groups. In all groups, the burn procedure was applied following the comb burn model. In Group 1, no postburn treatment was administered. In Group 2, physiological saline solution (0.3 cc) was injected intradermally and in Group 3, EGF (0.3 cc) was injected intradermally into stasis zone tissues after the burn procedure. Surviving tissue rates were 24.0% in Group 1, 25.3% in Group 2, and 70.2% in Group 3. The average numbers of cells stained with Nrf2, HO-1, and the number of apoptotic cells were 230, 150, and 17.5 in Group 1, 230, 145, and 15.0 in Group 2, and 370, 230, and 0 in Group 3, respectively. Values in Group 3 were found to be statistically significantly different than those of Groups 1 and 2; there was no difference between Groups 1 and 2. This study shows that EGF protects zone of stasis tissue from burn damage.
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Affiliation(s)
- Oktay Kaya
- Department of Physiology, Trakya University School of Medicine, Edirne, Turkey
| | - Erkan Orhan
- Department of Plastic Surgery, Gaziantep University, School of Medicine, Gaziantep, Turkey
| | - Melike Sapmaz-Metin
- Department of Histology and Embryology, Trakya University, School of Medicine, Edirne, Turkey
| | | | - Özgür Gündüz
- Department of Medical Pharmacology, Trakya University, School of Medicine, Edirne, Turkey
| | - Bilgehan Aydın
- Department of Plastic Surgery, Yeditepe University School of Medicine, Istanbul, Turkey
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17
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Uluer ET, Vatansever HS, Aydede H, Ozbilgin MK. Keratinocytes derived from embryonic stem cells induce wound healing in mice. Biotech Histochem 2018; 94:189-198. [PMID: 30460873 DOI: 10.1080/10520295.2018.1541479] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
The skin plays an important role in defending the body against the environment. Treatments for burns and skin injuries that use autologous or allogenic skin grafts derived from adult or embryonic stem cells are promising. Embryonic stem cells are candidates for regenerative and reparative medicine. We investigated the utility of keratinocyte-like cells, which are differentiated from mouse embryonic stem cells, for wound healing using a mouse surgical wound model. Mice were allocated to the following groups: experimental, in which dressing and differentiated cells were applied after the surgical wound was created; control, in which only the surgical wound was created; sham, in which only the dressing was applied after the surgical wound was created; and untreated animal controls with healthy skin. Biopsies were taken from each group on days 3, 5 and 7 after cell transfer. Samples were fixed in formalin, then stained with Masson's trichrome and primary antibodies to interleukin-8 (IL-8), fibroblast growth factor-2 (FGF-2), monocyte chemoattractant protein-1 (MCP-1), collagen-1 and epidermal growth factor (EGF) using the indirect immunoperoxidase technique for light microscopy. Wound healing was faster in the experimental group compared to the sham and control groups. The experimental group exhibited increased expression of IL-8, FGF-2 and MCP-1 during early stages of wound healing (inflammation) and collagen-1 and EGF expression during late stages of wound healing (proliferation and remodeling). Keratinocytes derived from embryonic stem cells improved wound healing and influenced the wound healing stages.
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Affiliation(s)
- E T Uluer
- a Departments of Histology and Embryology, Faculty of Medicine , Manisa Celal Bayar University , Manisa , Turkey
| | - H S Vatansever
- a Departments of Histology and Embryology, Faculty of Medicine , Manisa Celal Bayar University , Manisa , Turkey
| | - H Aydede
- b Departments of General Surgery, Faculty of Medicine , Manisa Celal Bayar University , Manisa , Turkey
| | - M K Ozbilgin
- a Departments of Histology and Embryology, Faculty of Medicine , Manisa Celal Bayar University , Manisa , Turkey
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18
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Tomic-Canic M, Wong LL, Smola H. The epithelialisation phase in wound healing: options to enhance wound closure. J Wound Care 2018; 27:646-658. [DOI: 10.12968/jowc.2018.27.10.646] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Majana Tomic-Canic
- Professor and Vice Chair of Research; Director, Wound Healing and Regenerative Medicine Research Program; Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, University of Miami, Miller School of Medicine, Miami, Florida, US
| | - Lulu L. Wong
- MD Candidate; Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, University of Miami, Miller School of Medicine, Miami, Florida, US
| | - Hans Smola
- Professor of Dermatology, Medical Director, PAUL HARTMANN AG, Heidenheim and Department of Dermatology, University of Cologne, Cologne, Germany
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19
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Stone Ii R, Natesan S, Kowalczewski CJ, Mangum LH, Clay NE, Clohessy RM, Carlsson AH, Tassin DH, Chan RK, Rizzo JA, Christy RJ. Advancements in Regenerative Strategies Through the Continuum of Burn Care. Front Pharmacol 2018; 9:672. [PMID: 30038569 PMCID: PMC6046385 DOI: 10.3389/fphar.2018.00672] [Citation(s) in RCA: 78] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Accepted: 06/05/2018] [Indexed: 01/09/2023] Open
Abstract
Burns are caused by several mechanisms including flame, scald, chemical, electrical, and ionizing and non-ionizing radiation. Approximately half a million burn cases are registered annually, of which 40 thousand patients are hospitalized and receive definitive treatment. Burn care is very resource intensive as the treatment regimens and length of hospitalization are substantial. Burn wounds are classified based on depth as superficial (first degree), partial-thickness (second degree), or full-thickness (third degree), which determines the treatment necessary for successful healing. The goal of burn wound care is to fully restore the barrier function of the tissue as quickly as possible while minimizing infection, scarring, and contracture. The aim of this review is to highlight how tissue engineering and regenerative medicine strategies are being used to address the unique challenges of burn wound healing and define the current gaps in care for both partial- and full-thickness burn injuries. This review will present the current standard of care (SOC) and provide information on various treatment options that have been tested pre-clinically or are currently in clinical trials. Due to the complexity of burn wound healing compared to other skin injuries, burn specific treatment regimens must be developed. Recently, tissue engineering and regenerative medicine strategies have been developed to improve skin regeneration that can restore normal skin physiology and limit adverse outcomes, such as infection, delayed re-epithelialization, and scarring. Our emphasis will be centered on how current clinical and pre-clinical research of pharmacological agents, biomaterials, and cellular-based therapies can be applied throughout the continuum of burn care by targeting the stages of wound healing: hemostasis, inflammation, cell proliferation, and matrix remodeling.
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Affiliation(s)
- Randolph Stone Ii
- Combat Trauma and Burn Injury Research, US Army Institute of Surgical Research San Antonio, TX, United States
| | - Shanmugasundaram Natesan
- Combat Trauma and Burn Injury Research, US Army Institute of Surgical Research San Antonio, TX, United States
| | - Christine J Kowalczewski
- Combat Trauma and Burn Injury Research, US Army Institute of Surgical Research San Antonio, TX, United States
| | - Lauren H Mangum
- Combat Trauma and Burn Injury Research, US Army Institute of Surgical Research San Antonio, TX, United States.,Extremity Trauma and Regenerative Medicine, US Army Institute of Surgical Research San Antonio, TX, United States
| | - Nicholas E Clay
- Combat Trauma and Burn Injury Research, US Army Institute of Surgical Research San Antonio, TX, United States
| | - Ryan M Clohessy
- Combat Trauma and Burn Injury Research, US Army Institute of Surgical Research San Antonio, TX, United States
| | - Anders H Carlsson
- Dental and Craniofacial Trauma Research, US Army Institute of Surgical Research San Antonio, TX, United States
| | - David H Tassin
- Dental and Craniofacial Trauma Research, US Army Institute of Surgical Research San Antonio, TX, United States
| | - Rodney K Chan
- Dental and Craniofacial Trauma Research, US Army Institute of Surgical Research San Antonio, TX, United States
| | - Julie A Rizzo
- Burn Flight Team, US Army Institute of Surgical Research San Antonio, TX, United States
| | - Robert J Christy
- Combat Trauma and Burn Injury Research, US Army Institute of Surgical Research San Antonio, TX, United States
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20
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Campos JC, Cunha JD, Ferreira DC, Reis S, Costa PJ. Challenges in the local delivery of peptides and proteins for oral mucositis management. Eur J Pharm Biopharm 2018; 128:131-146. [PMID: 29702221 DOI: 10.1016/j.ejpb.2018.04.025] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2018] [Revised: 04/21/2018] [Accepted: 04/23/2018] [Indexed: 12/20/2022]
Abstract
Oral mucositis, a common inflammatory side effect of oncological treatments, is a disorder of the oral mucosa that can cause painful ulcerations, local motor disabilities, and an increased risk of infections. Due to the discomfort it produces and the associated health risks, it can lead to cancer treatment restrains, such as the need for dose reduction, cycle delays or abandonment. Current mucositis management has low efficiency in prevention and treatment. A topical drug application for a local action can be a more effective approach than systemic routes when addressing oral cavity pathologies. Local delivery of growth factors, antibodies, and anti-inflammatory cytokines have shown promising results. However, due to the peptide and protein nature of these novel agents, and the several anatomic, physiological and environmental challenges of the oral cavity, their local action might be limited when using traditional delivering systems. This review is an awareness of the issues and strategies in the local delivery of macromolecules for the management of oral mucositis.
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Affiliation(s)
- João C Campos
- UCIBIO, REQUIMTE, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Portugal(1).
| | - João D Cunha
- UCIBIO, REQUIMTE, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Portugal(1)
| | - Domingos C Ferreira
- UCIBIO, REQUIMTE, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Portugal(1)
| | - Salette Reis
- LAQV, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Portugal(1)
| | - Paulo J Costa
- UCIBIO, REQUIMTE, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Portugal(1)
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21
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Yoon D, Yoon D, Cha HJ, Lee JS, Chun W. Enhancement of wound healing efficiency mediated by artificial dermis functionalized with EGF or NRG1. ACTA ACUST UNITED AC 2018; 13:045007. [PMID: 29386409 DOI: 10.1088/1748-605x/aaac37] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
The use of artificial dermis as a skin substitute is a field of active study, as acellular dermal matrices from cadavers are susceptible to infection owing to their human origin. One such alternative dermal replacement scaffold, INSUREGRAF®, is derived primarily from extracellular matrix proteins such as collagen and elastin and has been clinically used to treat severe skin wounds such as burns. This scaffold has proven to be useful to minimize wound contraction and scar formation owing to its biocompatibility, interconnected pore structure, sufficient biodegradability, and suitable mechanical properties. However, INSUREGRAF® does not provide scar-free wound healing in cases of severe skin damage such as full-thickness (FT) excision. Considering that the efficient recruitment of fibroblasts and keratinocytes into a wound site represents a critical step in the regeneration of damaged skin, we attempted to enhance the efficiency for wound healing by fabricating growth factor-functionalized INSUREGRAF®. In particular, we utilized epidermal growth factor (EGF) and an EGF family member, neuregulin-1 (NRG1), not previously studied in the context of wound healing, whose cellular role is to promote proliferation and migration in fibroblasts and keratinocytes. Both artificial dermis-growth factor combinations led to efficient recruitment of fibroblasts and keratinocytes into a wound site during the early steps of skin regeneration. Notably, EGF- or NRG1-functionalized INSUREGRAF® induced rapid proliferation of skin cells in an ERK pathway-dependent manner and exhibited efficient wound healing in a Sprague-Dawley rat FT excision and grafting model. These results provide the foundation for expanding the use of growth factor-functionalized INSUREGRAF® to clinical application in cases of severe skin injury.
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Affiliation(s)
- Dogeon Yoon
- Burn Institute, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Republic of Korea
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22
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Andrews CJ, Cuttle L. Comparing the reported burn conditions for different severity burns in porcine models: a systematic review. Int Wound J 2017; 14:1199-1212. [PMID: 28736990 PMCID: PMC7949960 DOI: 10.1111/iwj.12786] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Accepted: 05/31/2017] [Indexed: 12/25/2022] Open
Abstract
There are many porcine burn models that create burns using different materials (e.g. metal, water) and different burn conditions (e.g. temperature and duration of exposure). This review aims to determine whether a pooled analysis of these studies can provide insight into the burn materials and conditions required to create burns of a specific severity. A systematic review of 42 porcine burn studies describing the depth of burn injury with histological evaluation is presented. Inclusion criteria included thermal burns, burns created with a novel method or material, histological evaluation within 7 days post-burn and method for depth of injury assessment specified. Conditions causing deep dermal scald burns compared to contact burns of equivalent severity were disparate, with lower temperatures and shorter durations reported for scald burns (83°C for 14 seconds) compared to contact burns (111°C for 23 seconds). A valuable archive of the different mechanisms and materials used for porcine burn models is presented to aid design and optimisation of future models. Significantly, this review demonstrates the effect of the mechanism of injury on burn severity and that caution is recommended when burn conditions established by porcine contact burn models are used by regulators to guide scald burn prevention strategies.
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Affiliation(s)
- Christine J Andrews
- Centre for Children's Burns and Trauma ResearchThe University of Queensland, Centre for Children's Health ResearchSouth BrisbaneQLDAustralia
| | - Leila Cuttle
- Centre for Children's Burns and Trauma ResearchQueensland University of Technology, Institute of Health and Biomedical Innovation and Centre for Children's Health ResearchSouth BrisbaneQLDAustralia
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23
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Zhu Q, Mangukiya HB, Mashausi DS, Guo H, Negi H, Merugu SB, Wu Z, Li D. Anterior gradient 2 is induced in cutaneous wound and promotes wound healing through its adhesion domain. FEBS J 2017; 284:2856-2869. [PMID: 28665039 DOI: 10.1111/febs.14155] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2017] [Revised: 06/19/2017] [Accepted: 06/27/2017] [Indexed: 12/17/2022]
Abstract
Anterior gradient 2 (AGR2), a member of protein disulfide isomerase (PDI) family, is both located in cytoplasm and secreted into extracellular matrix. The orthologs of AGR2 have been linked to limb regeneration in newt and wound healing in zebrafish. In mammals, AGR2 influences multiple cell signaling pathways in tumor formation and in normal cell functions related to new tissue formation like angiogenesis. However, the function of AGR2 in mammalian wound healing remains unknown. This study aimed to investigate AGR2 expression and its function during skin wound healing and the possible application of external AGR2 in cutaneous wound to accelerate the healing process. Our results showed that AGR2 expression was induced in the migrating epidermal tongue and hyperplastic epidermis after skin excision. Topical application of recombinant AGR2 significantly accelerated wound-healing process by increasing the migration of keratinocytes (Kera.) and the recruitment of fibroblasts (Fibro.) near the wounded area. External AGR2 also promoted the migration of Kera. and Fibro. in vitro in a dose-dependent manner. The adhesion domain of AGR2 was required for the formation of focal adhesions in migrating Fibro., leading to the directional migration along AGR2 gradient. These results indicate that recombinant AGR2 accelerates skin wound healing through regulation of Kera. and Fibro. migration, thus demonstrating its potential utility as an alternative strategy of the therapeutics to accelerate the healing of acute or chronic skin wounds.
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Affiliation(s)
- Qi Zhu
- School of Pharmacy, Shanghai Jiao Tong University, China
| | | | | | - Hao Guo
- School of Pharmacy, Shanghai Jiao Tong University, China
| | - Hema Negi
- School of Pharmacy, Shanghai Jiao Tong University, China
| | | | - Zhenghua Wu
- School of Pharmacy, Shanghai Jiao Tong University, China
| | - Dawei Li
- School of Pharmacy, Shanghai Jiao Tong University, China.,Engineering Research Center of Cell and Therapeutic Antibody of Ministry of Education, Shanghai Jiao Tong University, China
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24
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Shin S, Shin JU, Lee Y, Chung WY, Nam KH, Kwon TG, Lee JH. The Effects of Multi-Growth Factors-Containing Cream on Post-Thyroidectomy Scars: A Preliminary Study. Ann Dermatol 2017; 29:314-320. [PMID: 28566908 PMCID: PMC5438938 DOI: 10.5021/ad.2017.29.3.314] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Revised: 07/29/2016] [Accepted: 08/29/2016] [Indexed: 11/08/2022] Open
Abstract
Background Growth factors play important roles in wound healing. However, the evidence for the effects of growth factors on post-thyroidectomy scars is limited. Objective We performed a prospective study to assess the preventive and therapeutic effect of a multi-growth factor (MGF)-containing cream on post-thyroidectomy scars. Methods Twenty-one patients with thyroidectomy scars applied MGF cream twice a day. We assessed the changes in erythema, pigmentation, skin elasticity, and skin hydration status using the erythema index, melanin index, cutometer, and corneometer, respectively. In addition, Vancouver scar scale (VSS) and patient satisfaction were assessed at 10 days after surgery (baseline), 2 weeks, 6 weeks, and 12 weeks after baseline. Results The mean total VSS scores were significantly lower at 6 weeks (3.24±1.51 vs. 1.91±1.38) and 12 weeks (3.24±1.51 vs. 1.71±1.59) compared to the baseline. The degree of pigmentation was significantly lower at 12 weeks compared to the baseline, and the skin elasticity, and the skin hydration status were significantly higher at 12 weeks compared to the baseline. Over 85% of the patients were satisfied with the use of MGF cream without any adverse effect. Conclusion MGF cream might have additive or supportive effect for scar formation after thyroidectomy.
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Affiliation(s)
- Sungsik Shin
- Department of Dermatology, Severance Hospital, Seoul, Korea.,Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Jung U Shin
- Department of Dermatology, Severance Hospital, Seoul, Korea.,Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Youngin Lee
- Department of Dermatology, Severance Hospital, Seoul, Korea.,Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Woong Youn Chung
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.,Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
| | - Kee-Hyun Nam
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.,Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
| | - Tae Gwang Kwon
- Department of Dermatology, Severance Hospital, Seoul, Korea.,Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Ju Hee Lee
- Department of Dermatology, Severance Hospital, Seoul, Korea.,Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea
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Pang C, Ibrahim A, Bulstrode NW, Ferretti P. An overview of the therapeutic potential of regenerative medicine in cutaneous wound healing. Int Wound J 2017; 14:450-459. [PMID: 28261962 DOI: 10.1111/iwj.12735] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Revised: 02/05/2017] [Accepted: 02/10/2017] [Indexed: 12/14/2022] Open
Abstract
The global burden of disease associated with wounds is an increasingly significant public health concern. Current treatments are often expensive, time-consuming and limited in their efficacy in chronic wounds. The challenge of overcoming current barriers associated with wound care requires innovative management techniques. Regenerative medicine is an emerging field of research that focuses on the repair, replacement or regeneration of cells, tissues or organs to restore impaired function. This article provides an overview of the pathophysiology of wound healing and reviews the latest evidence on the application of the principal components of regenerative medicine (growth factors, stem cell transplantation, biomaterials and tissue engineering) as therapeutic targets. Improved knowledge and understanding of the pathophysiology of wound healing has pointed to new therapeutic targets. Regenerative medicine has the potential to underpin the design of specific target therapies in acute and chronic wound healing. This personalised approach could eventually reduce the burden of disease associated with wound healing. Further evidence is required in the form of large animal studies and clinical trials to assess long-term efficacy and safety of these new treatments.
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Affiliation(s)
- Calver Pang
- Department of Surgery Surgical Research, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Amel Ibrahim
- Stem Cells and Regenerative Medicine Section, UCL GOS Institute of Child Health, University College London, London, UK.,Great Ormond Street Hospital for Children, London, UK
| | - Neil W Bulstrode
- Stem Cells and Regenerative Medicine Section, UCL GOS Institute of Child Health, University College London, London, UK.,Great Ormond Street Hospital for Children, London, UK
| | - Patrizia Ferretti
- Stem Cells and Regenerative Medicine Section, UCL GOS Institute of Child Health, University College London, London, UK.,Great Ormond Street Hospital for Children, London, UK
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Abstract
BACKGROUND Keloid and hypertrophic scars represent an aberrant response to the wound healing process. These scars are characterized by dysregulated growth with excessive collagen formation, and can be cosmetically and functionally disruptive to patients. OBJECTIVE Objectives are to describe the pathophysiology of keloid and hypertrophic scar, and to compare differences with the normal wound healing process. The classification of keloids and hypertrophic scars are then discussed. Finally, various treatment options including prevention, conventional therapies, surgical therapies, and adjuvant therapies are described in detail. MATERIALS AND METHODS Literature review was performed identifying relevant publications pertaining to the pathophysiology, classification, and treatment of keloid and hypertrophic scars. RESULTS Though the pathophysiology of keloid and hypertrophic scars is not completely known, various cytokines have been implicated, including interleukin (IL)-6, IL-8, and IL-10, as well as various growth factors including transforming growth factor-beta and platelet-derived growth factor. Numerous treatments have been studied for keloid and hypertrophic scars,which include conventional therapies such as occlusive dressings, compression therapy, and steroids; surgical therapies such as excision and cryosurgery; and adjuvant and emerging therapies including radiation therapy, interferon, 5-fluorouracil, imiquimod, tacrolimus, sirolimus, bleomycin, doxorubicin, transforming growth factor-beta, epidermal growth factor, verapamil, retinoic acid, tamoxifen, botulinum toxin A, onion extract, silicone-based camouflage, hydrogel scaffold, and skin tension offloading device. CONCLUSION Keloid and hypertrophic scars remain a challenging condition, with potential cosmetic and functional consequences to patients. Several therapies exist which function through different mechanisms. Better understanding into the pathogenesis will allow for development of newer and more targeted therapies in the future.
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Kim JW, Kim MG, Lee HJ, Koh Y, Kwon JH, Kim I, Park S, Kim BK, Oh JM, Kim KI, Yoon SS. Topical Recombinant Human Epidermal Growth Factor for Oral Mucositis Induced by Intensive Chemotherapy with Hematopoietic Stem Cell Transplantation: Final Analysis of a Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial. PLoS One 2017; 12:e0168854. [PMID: 28045958 PMCID: PMC5207736 DOI: 10.1371/journal.pone.0168854] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2016] [Accepted: 11/22/2016] [Indexed: 01/23/2023] Open
Abstract
The aim of this study was to evaluate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) oral spray for oral mucositis (OM) induced by intensive chemotherapy with hematopoietic stem cell transplantation. In this phase 2 study, patients were randomized to either rhEGF (50 microg/mL) or placebo in a 1:1 ratio. The primary endpoint was incidence of National Cancer Institute (NCI) grade ≥2 OM. A total of 138 patients were enrolled in this study. In the intention-to-treat analysis, rhEGF did not reduce the incidence of NCI grade ≥2 OM (p = 0.717) nor reduce its duration (p = 0.725). Secondary endpoints including the day of onset and duration of NCI grade ≥2 OM, the incidence of NCI grade ≥3 OM and its duration, and patient-reported quality of life were also similar between the two groups. In the per-protocol analysis, however, the duration of opioid analgesic use was shorter in the rhEGF group (p = 0.036), and recipients in the rhEGF group required a lower cumulative dose of opioid analgesics than those in the placebo group (p = 0.046), among patients with NCI grade ≥2 OM. Adverse events were mild and transient. This study found no evidence to suggest that rhEGF oral spray reduces the incidence of OM. However, further studies are needed to investigate the effect of rhEGF on OM-induced pain reduction after intensive chemotherapy.
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Affiliation(s)
- Ji-Won Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Myeong Gyu Kim
- College of Pharmacy, Seoul National University, Seoul, Republic of Korea
| | - Hyun Jung Lee
- Department of Internal Medicine, Dongguk University Ilsan Medical Center, Goyang, Republic of Korea
| | - Youngil Koh
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
- Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
- Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Ji-Hyun Kwon
- Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea
| | - Inho Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
- Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
- Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Seonyang Park
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
- Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
- Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Byoung Kook Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
- Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
- Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jung Mi Oh
- College of Pharmacy, Seoul National University, Seoul, Republic of Korea
- Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
| | - Kyung Im Kim
- College of Pharmacy, Korea University, Sejong, Republic of Korea
- Biomedical Research Center, Korea University Guro Hospital, Seoul, Republic of Korea
- * E-mail: (SSY); (KIK)
| | - Sung-Soo Yoon
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
- Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
- Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
- * E-mail: (SSY); (KIK)
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Razzak MA, Hossain MS, Radzi ZB, Yahya NAB, Czernuszka J, Rahman MT. Cellular and Molecular Responses to Mechanical Expansion of Tissue. Front Physiol 2016; 7:540. [PMID: 27899897 PMCID: PMC5111402 DOI: 10.3389/fphys.2016.00540] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Accepted: 10/27/2016] [Indexed: 01/08/2023] Open
Abstract
The increased use of tissue expander in the past decades and its potential market values in near future give enough reasons to sum up the consequences of tissue expansion. Furthermore, the patients have the right to know underlying mechanisms of adaptation of inserted biomimetic, its bioinspired materials and probable complications. The mechanical strains during tissue expansion are related to several biological phenomena. Tissue remodeling during the expansion is highly regulated and depends on the signal transduction. Any alteration may lead to tumor formation, necrosis and/or apoptosis. In this review, stretch induced cell proliferation, apoptosis, the roles of growth factors, stretch induced ion channels, and roles of second messengers are organized. It is expected that readers from any background can understand and make a decision about tissue expansion.
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Affiliation(s)
- Muhammad Abdur Razzak
- Department of Children's Dentistry and Orthodontics, Faculty of Dentistry, University of Malaya Kuala Lumpur, Malaysia
| | - Md Sanower Hossain
- Department of Children's Dentistry and Orthodontics, Faculty of Dentistry, University of Malaya Kuala Lumpur, Malaysia
| | - Zamri Bin Radzi
- Department of Children's Dentistry and Orthodontics, Faculty of Dentistry, University of Malaya Kuala Lumpur, Malaysia
| | - Noor Azlin B Yahya
- Department of Children's Dentistry and Orthodontics, Faculty of Dentistry, University of Malaya Kuala Lumpur, Malaysia
| | - Jan Czernuszka
- Department of Materials, University of Oxford Oxford, UK
| | - Mohammad T Rahman
- Department of Children's Dentistry and Orthodontics, Faculty of Dentistry, University of Malaya Kuala Lumpur, Malaysia
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Shin S, Shin JU, Lee Y, Kwon TG, Lee JH. The effects of a multigrowth factor-containing cream on recovery after laser treatment: a double-blinded, randomized, split-face controlled study. J Cosmet Dermatol 2016; 16:76-83. [DOI: 10.1111/jocd.12285] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/18/2016] [Indexed: 12/13/2022]
Affiliation(s)
- Sungsik Shin
- Department of Dermatology; Severance Hospital & Cutaneous Biology Research Institute; Yonsei University College of Medicine; Seoul Korea
| | - Jung U Shin
- Department of Dermatology; Severance Hospital & Cutaneous Biology Research Institute; Yonsei University College of Medicine; Seoul Korea
| | - Youngin Lee
- Department of Dermatology; Severance Hospital & Cutaneous Biology Research Institute; Yonsei University College of Medicine; Seoul Korea
| | - Tae Gwang Kwon
- Department of Dermatology; Severance Hospital & Cutaneous Biology Research Institute; Yonsei University College of Medicine; Seoul Korea
| | - Ju Hee Lee
- Department of Dermatology; Severance Hospital & Cutaneous Biology Research Institute; Yonsei University College of Medicine; Seoul Korea
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Birincioğlu İ, Akbaba M, Alver A, Kul S, Özer E, Turan N, Şentürk A, İnce İ. Determination of skin wound age by using cytokines as potential markers. J Forensic Leg Med 2016; 44:14-19. [PMID: 27589380 DOI: 10.1016/j.jflm.2016.08.011] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Revised: 08/16/2016] [Accepted: 08/23/2016] [Indexed: 12/20/2022]
Abstract
Interleukin-1 beta (IL-1β), IL-6, tumour necrosis factor-alpha (TNF-α) and epidermal growth factor (EGF) play important roles in the wound healing process. In the present study, human wound specimens (n = 50) were collected from cases of death due to injuries from firearms, penetrating trauma by sharp objects and blunt trauma with a known time of injury and death identified by forensic autopsy. Full-thickness tissue specimens were obtained from injured skin sites, and equally sized intact tissues obtained from the same person were used as controls. Protein determination was performed using ELISA according to the Bradford method for each specimen, and results were provided for individual proteins. IL-1β levels did not reach statistical significance in any of the wound groups and were not markedly higher than those in the control group. However, IL-6 showed a biphasic pattern and reached statistical significance in the group with wounds less than 30 min old and in the group with wounds more than 18 h old. IL-6 was consistently higher in all wound groups than in the control group. TNF-α showed a statistically significant increase within the first 30 min and remained at a high level in all groups except for those with wounds 2-4 h old. On the other hand, EGF was high in all groups excluding those with wounds 2-4 h old and more than 18 h old, but statistical significance was not reached. Our results suggest that IL-6 and TNF-α in particular may be used as early-phase markers. We believe that IL-1β and EGF should be more extensively evaluated in further studies.
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Affiliation(s)
- İsmail Birincioğlu
- Department of Forensic Medicine, Faculty of Medicine, Karadeniz Technical University, Turkey
| | - Murat Akbaba
- Department of Forensic Medicine, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey.
| | - Ahmet Alver
- Department of Medical Chemistry, Faculty of Medicine, Karadeniz Technical University, Turkey
| | - Seval Kul
- Department of Biostatistics, Faculty of Medicine, University of Gaziantep, Turkey
| | - Erdal Özer
- Department of Forensic Medicine, Faculty of Medicine, Karadeniz Technical University, Turkey
| | - Nurşen Turan
- Department of Forensic Medicine, Faculty of Medicine, Marmara University, Turkey
| | - Ayşe Şentürk
- Department of Medical Chemistry, Faculty of Medicine, Karadeniz Technical University, Turkey
| | - İmran İnce
- Department of Medical Chemistry, Faculty of Medicine, Karadeniz Technical University, Turkey
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31
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Ricotti G, Tucci M, Pugnaloni A, Biagini G, Belligolli A, Bertani A, Castagnani R, Castaldini C. Epidermal Growth Factor in Cutaneous Repair Processes. J BIOACT COMPAT POL 2016. [DOI: 10.1177/088391159200700107] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Donor areas on patients undergoing plastic surgery were treated with epidermal growth factor (EGF) to stimulate tissue regeneration. Mor phometric analyses showed that cutaneous explants, treated with EGF, pre sented a higher number of microvessels ( p < 0.01) and mesenchimal cells ( p < 0.01), than untreated areas, while EGF did not improve epidermal thick ening. By electron microscopy, better histoarchitectural maturation of cellular and extracellular dermal compartments was observed after EGF application. This work provides evidence that EGF does stimulate skin repair by promoting the formation of mature cutaneous tissue.
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Affiliation(s)
- G. Ricotti
- Faculty of Medicine University of Ancona Via P. Ranieri-Monte d'Ago 60131 Ancona Italy
| | - M.G. Tucci
- Faculty of Medicine University of Ancona Via P. Ranieri-Monte d'Ago 60131 Ancona Italy
| | - A. Pugnaloni
- Faculty of Medicine University of Ancona Via P. Ranieri-Monte d'Ago 60131 Ancona Italy
| | - G. Biagini
- Faculty of Medicine University of Ancona Via P. Ranieri-Monte d'Ago 60131 Ancona Italy
| | - A. Belligolli
- Faculty of Medicine University of Ancona Via P. Ranieri-Monte d'Ago 60131 Ancona Italy
| | - A. Bertani
- Faculty of Medicine University of Ancona Via P. Ranieri-Monte d'Ago 60131 Ancona Italy
| | - R. Castagnani
- C.E.D.U.A. Faculty of Engineering University of Ancona Italy
| | - C. Castaldini
- Institute of Histology Faculty of Medicine University of Bologna Italy
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Esquirol Caussa J, Herrero Vila E. Un enfoque para el tratamiento de las úlceras de origen vascular: revisión y papel del factor de crecimiento epidérmico. ANGIOLOGIA 2016. [DOI: 10.1016/j.angio.2015.10.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Kim CS, Mitchell IP, Desotell AW, Kreeger PK, Masters KS. Immobilized epidermal growth factor stimulates persistent, directed keratinocyte migration via activation of PLCγ1. FASEB J 2016; 30:2580-90. [PMID: 27025961 DOI: 10.1096/fj.201600252] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 03/21/2016] [Indexed: 01/19/2023]
Abstract
Epidermal growth factor (EGF) is a critical element in dermal repair, but EGF-containing wound dressings have not been successful clinically. However, these dressings have delivered only soluble EGF, and the native environment provides both soluble and matrix-bound EGF. To address our hypothesis that tethered EGF can stimulate cell behaviors not achievable with soluble EGF, we examined single-cell movement and signaling in human immortalized HaCaT keratinocytes treated with soluble or immobilized EGF. Although both EGF treatments increased collective sheet displacement and individual cell speed, only cells treated with immobilized EGF exhibited directed migration, as well as 2-fold greater persistence compared with soluble EGF. Immunofluorescence showed altered EGF receptor (EGFR) trafficking, where EGFR remained membrane-localized in the immobilized EGF condition. Cells treated with soluble EGF demonstrated higher phosphorylated ERK1/2, and cells on immobilized EGF exhibited higher pPLCγ1, which was localized at the leading edge. Treatment with U0126 inhibited migration in both conditions, demonstrating that ERK1/2 activity was necessary but not responsible for the observed differences. In contrast, PLCγ1 inhibition with U73122 significantly decreased persistence on immobilized EGF. Combined, these results suggest that immobilized EGF increases collective keratinocyte displacement via an increase in single-cell migration persistence resulting from altered EGFR trafficking and PLCγ1 activation.-Kim, C. S., Mitchell, I. P., Desotell, A. W., Kreeger, P. K., Masters, K. S. Immobilized epidermal growth factor stimulates persistent, directed keratinocyte migration via activation of PLCγ1.
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Affiliation(s)
- Chloe S Kim
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Isaiah P Mitchell
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Anthony W Desotell
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Pamela K Kreeger
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Kristyn S Masters
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA
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Theunissen D, Seymour B, Forder M, Cox SG, Rode H. Measurements in wound healing with observations on the effects of topical agents on full thickness dermal incised wounds. Burns 2016; 42:556-63. [PMID: 26899619 DOI: 10.1016/j.burns.2015.09.014] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Revised: 05/29/2015] [Accepted: 09/19/2015] [Indexed: 10/22/2022]
Abstract
INTRODUCTION A multitude of topical wound treatments are used today. Although it is well established that the micro-environment of healing wounds can be altered to improve healing, it is difficult to measure the subtle differences in outcome where therapies are compared. METHOD We compared wound healing properties between four different topical agents in surgically incised wounds in a pig model. The four topical agents, 5% Povidone-Iodine cream, 1% Silver-Sulphadiazine, 2% Mupirocin, and 1% Silver-Sulphadiazine plus 1mg/100g recombinant-human epithelial growth factor (EGF) were randomly assigned to four test animals each. Test agents were compared to each other and to untreated controls. We investigated existing and new methodologies of measurement of wound healing: clinical and histological visual scoring systems, immuno-histochemistry, and computerized image analysis of the wounds on days 3, 7, and 28. RESULTS All agents were found to have improved healing rates with better cellular architecture. Healing was faster, histological appearance resembled normal architecture sooner, clinical appearance improved, mitotic activity was stimulated and more collagen was deposited in comparison to the wounds with no agents. EGF-treated wounds showed an increased rate of epithelisation, but the rate of healing did not correlate well with evaluation of cosmetic outcome. CONCLUSION Topical agents improve all aspects of wound healing. The addition of a human recombinant EGF to Silver-Sulphadiazine increases epithelial growth and amounts of collagen in the regenerating wounds at day 7.
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Affiliation(s)
- D Theunissen
- Department of Paediatric Surgery, Red Cross War Memorial Children's Hospital, University of Cape Town, South Africa
| | - B Seymour
- Department of Anatomical Pathology, Groote Schuur Hospital, NHLS, University of Cape Town, South Africa
| | - M Forder
- Department of Anatomical Pathology, Groote Schuur Hospital, NHLS, University of Cape Town, South Africa
| | - S G Cox
- Department of Paediatric Surgery, Red Cross War Memorial Children's Hospital, University of Cape Town, South Africa
| | - H Rode
- Department of Paediatric Surgery, Red Cross War Memorial Children's Hospital, University of Cape Town, South Africa.
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Mitchell AC, Briquez PS, Hubbell JA, Cochran JR. Engineering growth factors for regenerative medicine applications. Acta Biomater 2016; 30:1-12. [PMID: 26555377 PMCID: PMC6067679 DOI: 10.1016/j.actbio.2015.11.007] [Citation(s) in RCA: 243] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2015] [Revised: 10/27/2015] [Accepted: 11/06/2015] [Indexed: 01/10/2023]
Abstract
Growth factors are important morphogenetic proteins that instruct cell behavior and guide tissue repair and renewal. Although their therapeutic potential holds great promise in regenerative medicine applications, translation of growth factors into clinical treatments has been hindered by limitations including poor protein stability, low recombinant expression yield, and suboptimal efficacy. This review highlights current tools, technologies, and approaches to design integrated and effective growth factor-based therapies for regenerative medicine applications. The first section describes rational and combinatorial protein engineering approaches that have been utilized to improve growth factor stability, expression yield, biodistribution, and serum half-life, or alter their cell trafficking behavior or receptor binding affinity. The second section highlights elegant biomaterial-based systems, inspired by the natural extracellular matrix milieu, that have been developed for effective spatial and temporal delivery of growth factors to cell surface receptors. Although appearing distinct, these two approaches are highly complementary and involve principles of molecular design and engineering to be considered in parallel when developing optimal materials for clinical applications. STATEMENT OF SIGNIFICANCE Growth factors are promising therapeutic proteins that have the ability to modulate morphogenetic behaviors, including cell survival, proliferation, migration and differentiation. However, the translation of growth factors into clinical therapies has been hindered by properties such as poor protein stability, low recombinant expression yield, and non-physiological delivery, which lead to suboptimal efficacy and adverse side effects. To address these needs, researchers are employing clever molecular and material engineering and design strategies to both improve the intrinsic properties of growth factors and effectively control their delivery into tissue. This review highlights examples of interdisciplinary tools and technologies used to augment the therapeutic potential of growth factors for clinical applications in regenerative medicine.
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Affiliation(s)
- Aaron C Mitchell
- Department of Bioengineering, Stanford University, Stanford, CA, USA
| | - Priscilla S Briquez
- Institute for Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - Jeffrey A Hubbell
- Institute for Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Institute for Molecular Engineering, University of Chicago, Chicago, IL, USA; Materials Science Division, Argonne National Laboratory, Argonne, IL, USA.
| | - Jennifer R Cochran
- Department of Bioengineering, Stanford University, Stanford, CA, USA; Department of Chemical Engineering, Stanford University, Stanford, CA, USA.
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Huang X, Tang J, Xu J, Jia G, Liu G, Chen X, Cai J, Shang H, Zhao H. Supranutritional dietary selenium induced hyperinsulinemia and dyslipidemia via affected expression of selenoprotein genes and insulin signal-related genes in broiler. RSC Adv 2016. [DOI: 10.1039/c6ra14932d] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
The purpose of this study was to investigate the effects of supranutritional selenium (Se) on the mRNA expression of selenoprotein genes and insulin signal-related genes in the liver, muscle and pancreas of the broiler.
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Affiliation(s)
- Xiaofeng Huang
- Animal Nutrition Institute
- Sichuan Agricultural University
- Chengdu
- China
| | - Jiayong Tang
- Animal Nutrition Institute
- Sichuan Agricultural University
- Chengdu
- China
| | - Jingyang Xu
- Animal Nutrition Institute
- Sichuan Agricultural University
- Chengdu
- China
| | - Gang Jia
- Animal Nutrition Institute
- Sichuan Agricultural University
- Chengdu
- China
| | - Guangmang Liu
- Animal Nutrition Institute
- Sichuan Agricultural University
- Chengdu
- China
| | - Xiaoling Chen
- Animal Nutrition Institute
- Sichuan Agricultural University
- Chengdu
- China
| | - Jingyi Cai
- Animal Nutrition Institute
- Sichuan Agricultural University
- Chengdu
- China
| | - Haiying Shang
- Animal Nutrition Institute
- Sichuan Agricultural University
- Chengdu
- China
| | - Hua Zhao
- Animal Nutrition Institute
- Sichuan Agricultural University
- Chengdu
- China
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Songur MK, Akdemir O, Lineaweaver WC, Cavusoglu T, Ozsarac M, Aktug H, Songur E, Tiftikcioglu YO. Comparison of skin effects of immediate treatment modalities in experimentally induced hydrofluoric acid skin burns. Int Wound J 2015; 12:716-723. [PMID: 24618130 PMCID: PMC7950442 DOI: 10.1111/iwj.12214] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2013] [Revised: 12/10/2013] [Accepted: 12/12/2013] [Indexed: 02/03/2023] Open
Abstract
Hydrofluoric acid (HF) burns cause immediate damage and painful long-term sequellae. Traditionally, chelating agents have been used as the initial treatment for such burns. We have introduced epidermal growth factor (EGF) into an HF model to compare EGF with Ca(2+) and Mg(2+) treatments; 40 Sprague Dawley rats were divided into five groups. Each rat suffered a 6 × 4 cm(2) burn induced by 40% HF. Group 1 had no treatment, group 2 had saline injected beneath the burn, group 3 received magnesium sulphate injections, group 4 received calcium gluconate and group 5 received EGF. Specimens were evaluated via planimetry and biopsy at intervals of 4, 8, 24 and 72 hours. Fluid losses were significantly less in the Mg(2+) and EGF groups. The EGF group had the smallest burn area, least oedema, least polymorphonuclear granulocyte (PMN) infiltration, most angiogenesis and highest fibroblast proliferation of any group (P < 0·005). EGF limited HF damage morphologically and histologically more effectively than Ca(2+) or Mg(2+). This finding indicates that HF treatment via growth factors may be an improvement over chelation therapy.
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Affiliation(s)
- Meltem K Songur
- Department of Emergency Medicine, Ege University, Izmir, Turkey
| | - Ovunc Akdemir
- Department of Plastic Surgery, Ege University, Izmir, Turkey
| | - William C Lineaweaver
- Department Of Plastic, Reconstructive And Aesthetic Surgery, Joseph M. Still Burn and Reconstructive Center, Brandon, MS, USA
| | - Turker Cavusoglu
- Department of Histology and Embryology, Ege University, Izmir, Turkey
| | - Murat Ozsarac
- Department of Emergency Medicine, Ege University, Izmir, Turkey
| | - Huseyin Aktug
- Department of Histology and Embryology, Ege University, Izmir, Turkey
| | - Ecmel Songur
- Department of Plastic Surgery, Ege University, Izmir, Turkey
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Woo HD, Park KT, Kim EH, Heo Y, Jeong JH, Pyun DG, Choi CS, Lee JG, Han DK, Nah JW, Son TI. Preparation of UV-curable gelatin derivatives for drug immobilization on polyurethane foam: Development of wound dressing foam. Macromol Res 2015. [DOI: 10.1007/s13233-015-3131-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Phase II trial of epidermal growth factor ointment for patients with Erlotinib-related skin effects. Support Care Cancer 2015; 24:301-309. [PMID: 26041481 DOI: 10.1007/s00520-015-2783-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Accepted: 05/17/2015] [Indexed: 10/23/2022]
Abstract
PURPOSE The efficacy of erlotinib, the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has been demonstrated in patients with non-small cell lung cancer (NSCLC) and pancreatic cancer (PC). In the present study, we evaluated the effect of epidermal growth factor (EGF) ointment on erlotinib-related skin effects (ERSEs). METHODS This was an open-label, non-comparative, multicenter, phase II trial. The patients included those diagnosed with NSCLC or PC who were treated with erlotinib. The effectiveness of the ointment was defined as follows: (1) grade 2, 3, or 4 ERSEs downgraded to ≤ grade 1 or (2) grade 3 or 4 ERSEs downgraded to grade 2 and persisted for at least 2 weeks. RESULTS Fifty-two patients from seven institutes in Korea were enrolled with informed consent. The final assessment included 46 patients (30 males, 16 females). According to the definition of effectiveness, the EGF ointment was effective in 36 (69.2%) intention to treat patients. There were no statistically significant differences in the effectiveness of the EGF ointment by gender (p = 0.465), age (p = 0.547), tumor type (p = 0.085), erlotinib dosage (p = 0.117), and number of prior chemotherapy sessions (p = 0.547). The grading for the average National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) rating of rash/acne and itching improved from 2.02 ± 0.83 to 1.13 ± 0.89 and 1.52 ± 0.84 to 0.67 ± 0.90, respectively (p < 0.001). The most common reason for discontinuing the study was progression of cancer (37%). CONCLUSIONS Based on the results, the EGF ointment is effective for ERSEs, regardless of gender, age, type of tumor, and dosage of erlotinib. The EGF ointment evenly improved all kinds of symptoms of ERSEs. CLINICAL TRIAL REGISTRATION NO ClinicalTrials.gov identifier: NCT01593995.
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40
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Kim D, Kim SY, Mun SK, Rhee S, Kim BJ. Epidermal growth factor improves the migration and contractility of aged fibroblasts cultured on 3D collagen matrices. Int J Mol Med 2015; 35:1017-25. [PMID: 25647660 DOI: 10.3892/ijmm.2015.2088] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Accepted: 01/12/2015] [Indexed: 11/06/2022] Open
Abstract
Epidermal growth factor (EGF) plays a critical role in fibroblasts by stimulating the production of collagen and supports cell renewal through the interaction between keratinocytes and fibroblasts. It is well known that the contractile activity of fibroblasts is required for the remodeling of the extracellular matrix (ECM), which contributes to skin elasticity. However, the role of EGF in the contraction of aged fibroblasts under 3-dimensional (3D) culture conditions is not yet fully understood. In the present study, we demonstrated that young fibroblasts spread and proliferated more rapidly than aged fibroblasts under 2-dimensional (2D) culture conditions. Cell migration assay using a nested collagen matrix revealed that the migration of young fibroblasts was also greater than that of aged fibroblasts under 3D culture conditions. However, the addition of recombinant human EGF (rhEGF) resulted in the enhanced migration of aged fibroblasts; the migration rate was similar to that of the young fibroblasts. The aged fibroblasts showed decreased cluster formation compared with the young fibroblasts on the collagen matrix, which was improved by the addition of rhEGF. Furthermore, cell contraction assay revealed that the basal contractility of the aged fibroblasts was lower than that of the young fibroblasts; however, following treatment with rhEGF, the contractility was restored to levels similar or even higher to those of the young fibroblasts. Taken together, our results suggest that rhEGF is a potential renewal agent that acts to improve the migration and contraction of aged fibroblasts more efficiently than young fibroblasts under 3D culture conditions; thus, EGF may have valuable regenerative effects on aged skin.
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Affiliation(s)
- Daehwan Kim
- Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul, Republic of Korea
| | - So Young Kim
- Major in Biomedical Science, Department of Medicine, Graduate School, Chung-Ang University, Seoul, Republic of Korea
| | - Seog Kyun Mun
- Department of Otolaryngology-Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Sangmyung Rhee
- Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul, Republic of Korea
| | - Beom Joon Kim
- Major in Biomedical Science, Department of Medicine, Graduate School, Chung-Ang University, Seoul, Republic of Korea
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Dinh T, Braunagel S, Rosenblum BI. Growth factors in wound healing: the present and the future? Clin Podiatr Med Surg 2015; 32:109-19. [PMID: 25440422 DOI: 10.1016/j.cpm.2014.09.010] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Numerous clinical studies have confirmed the pivotal role growth factors play in wound healing and their diminished levels in the chronic wound. Despite promising early studies treating chronic wounds with growth factors, results with traditional bolus dosing of a single growth factor have yielded insignificant results. Disappointing results have been theorized to be the result of growth factors inherent short half-life, a hostile microenvironment rich in protease activity, and poor delivery mechanisms failing to deliver effective dosages in an appropriate temporal manner. Advances in tissue engineering and regenerative medicine have provided technologies capable of delivering multiple growth factors in a spatially oriented approach. These technologies include polymer systems, scaffolds, and hydrogels that have demonstrated improved response by target tissues when growth factors are delivered in this biomimetic fashion. With improved delivery systems, treatment of chronic wounds with growth factors has the potential to accelerate healing in a manner not previously realized with traditional delivery approaches.
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Affiliation(s)
- Thanh Dinh
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
| | | | - Barry I Rosenblum
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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42
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Shibata Y, Tanimoto Y. A review of improved fixation methods for dental implants. Part I: Surface optimization for rapid osseointegration. J Prosthodont Res 2015; 59:20-33. [DOI: 10.1016/j.jpor.2014.11.007] [Citation(s) in RCA: 74] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2014] [Revised: 11/05/2014] [Accepted: 11/17/2014] [Indexed: 10/24/2022]
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Bae IH, Park JW, Kim DY. Enhanced regenerative healing efficacy of a highly skin-permeable growth factor nanocomplex in a full-thickness excisional mouse wound model. Int J Nanomedicine 2014; 9:4551-67. [PMID: 25288883 PMCID: PMC4184407 DOI: 10.2147/ijn.s68399] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Exogenous administration of growth factors has potential benefits in wound healing; however, limited percutaneous absorption, inconsistent efficacy, and the need for high doses have hampered successful clinical use. To overcome these restrictions, we focused on the development of a topical formulation composed of highly skin-permeable multimeric nanocomplex of growth factors. In the present study, we fused low-molecular-weight protamine (LMWP) with epidermal growth factor (EGF), insulin-like growth factor 1 (IGF-I), and platelet-derived growth factor A ligand (PDGF-A) (producing recombinant [r]LMWP-EGF, rLMWP-IGF-I, and rLMWP-PDGF-A, respectively) via genetic modification. Then, we used in vitro cell proliferation studies to assess the biological activity and the benefits of the combination. The LMWP-conjugated growth factors were complexed with low-molecular-weight heparin (LMWH) and formulated with Poloxamer 188 as a delivery vehicle. After confirming the enhanced skin permeability, in vivo studies were performed to assess whether the LMWP-conjugated growth factor nanocomplex formulations accelerated the healing of full-thickness wounds in mice. The LMWP-conjugated growth factors were biologically equivalent to their native forms, and their combination induced greater fibroblast proliferation. rLMWP-EGF showed significantly enhanced permeability and cumulative permeation, and the rates for rLMWP-IGF-I and rLMWP-PDGF-A, across excised mouse skin, were 124% and 164% higher, respectively, than for the native forms. The LMWP-fused growth factors resulted in formation of nanocomplexes (23.51±1.12 nm in diameter) in combination with LMWH. Topical delivery of growth factors fused with LMWP accelerated wound re-epithelialization significantly, accompanied by the formation of healthy granulation tissue within 9 days compared with a free–growth factor complex or vehicle. Thus, the LMWP-conjugated growth factor nanocomplex can induce rapid, comprehensive healing and may be a candidate wound-healing therapeutic.
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Affiliation(s)
- Il-Hong Bae
- College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea
| | - Jin Woo Park
- College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Muan-gun, Jeonnam, Republic of Korea
| | - Dae-Yong Kim
- College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea
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Effect of recombinant human epidermal growth factor impregnated chitosan film on hemostasis and healing of blood vessels. Arch Plast Surg 2014; 41:466-71. [PMID: 25276636 PMCID: PMC4179348 DOI: 10.5999/aps.2014.41.5.466] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2014] [Revised: 04/11/2014] [Accepted: 05/08/2014] [Indexed: 11/30/2022] Open
Abstract
Background Bleeding can be a problem in wound debridement. In search for an effective hemostatic agent, we experimented with a chitosan film combined with the recombinant human epidermal growth factor (rh-EGF), hypothesizing that it would achieve effective hemostasis and simultaneously enhance arterial healing. Methods Forty-eight Sprague-Dawley rats were used, and 96 puncture wounds were made. The wounds were divided into the following four groups: treated with sterile gauze, treated with gelatin sponge, treated with chitosan, and treated with chitosan combined with rh-EGF. Immediate hemostasis was evaluated, and arterial healing was observed histologically. Results Groups B, C, and D showed a significant rate of immediate hemostasis as compared to group A (P<0.05), but there were no significant differences among groups B, C, and D. Histologically, only group D showed good continuity of the vessel wall after 1 week. It was the only group to show smooth muscle cell nuclei of the vessel wall. Conclusions We observed that chitosan has an effective hemostatic potential and the mix of rh-EGF and chitosan does not interfere with chitosan's hemostatic capabilities. We also identified enhanced healing of vessel walls when rh-EGF was added to chitosan. Further research based on these positive findings is needed to evaluate the potential use of this combination on difficult wounds like chronic diabetic ulcerations.
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Using recombinant human epidermal growth factor for the successful treatment of an excisional wound without a primary closure. Dermatol Surg 2014; 40:706-8. [PMID: 24852481 DOI: 10.1097/01.dss.0000450924.44391.d2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Zhang Y, Wang T, He J, Dong J. Growth factor therapy in patients with partial-thickness burns: a systematic review and meta-analysis. Int Wound J 2014; 13:354-66. [PMID: 25040572 DOI: 10.1111/iwj.12313] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2014] [Revised: 05/05/2014] [Accepted: 05/14/2014] [Indexed: 12/29/2022] Open
Abstract
Growth factor (GF) therapy has shown promise in treating a variety of refractory wounds. However, evidence supporting its routine use in burn injury remains uncertain. We performed this systematic review and meta-analysis assessing randomised controlled trials (RCTs) to investigate efficacy and safety of GFs in the management of partial-thickness burns. Electronic searches were conducted in PubMed and the Cochrane databases. Endpoint results analysed included wound healing and scar formation. Thirteen studies comprising a total of 1924 participants with 2130 wounds (1131 GF receiving patients versus 999 controls) were identified and included, evaluating the effect of fibroblast growth factor (FGF), epidermal growth factor (EGF) and granulocyte macrophage-colony stimulating factor (GM-CSF) on partial-thickness burns. Topical application of these agents significantly reduced healing time by 5·02 (95% confidence interval, 2·62 to 7·42), 3·12 (95% CI, 1·11 to 5·13) and 5·1 (95% CI, 4·02 to 6·18) days, respectively, compared with standard wound care alone. In addition, scar improvement following therapy with FGF and EGF was evident in terms of pigmentation, pliability, height and vascularity. No significant increase in adverse events was observed in patients receiving GFs. These results suggested that GF therapy could be an effective and safe add-on to standard wound care for partial-thickness burns. High-quality, adequately powered trials are needed to further confirm the conclusion.
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Affiliation(s)
- Yi Zhang
- Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tao Wang
- Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jinguang He
- Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiasheng Dong
- Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Şimşek G, Ciftci O, Karadag N, Karatas E, Kizilay A. Effects of topical phenytoin on nasal wound healing after mechanical trauma: An experimental study. Laryngoscope 2014; 124:E449-54. [PMID: 24978057 DOI: 10.1002/lary.24811] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Revised: 05/13/2014] [Accepted: 06/04/2014] [Indexed: 11/09/2022]
Abstract
OBJECTIVES/HYPOTHESIS Impaired postoperative wound healing is the second most common morbidity after synechia formation in endoscopic sinus surgery. The aim of this experimental study was to investigate the potential effects of topical phenytoin on wound healing after nasal mucosal trauma in rats. STUDY DESIGN An experimental study at the Inonu University Faculty of Medicine. METHODS Twenty-four rats were randomized into three groups: 1) phenytoin group (n = 8), 2) control group (n = 8), and 3) vehicle group (n = 8). After damaging the right nasal cavity, in the phenytoin group, 1% topical phenytoin cream was applied for 7 days. The rats in the control group did not receive any treatment. The vehicle group was treated with daily topical cold cream for 1 week. The rats were sacrificed at the end, and the nasal cavities were excised. Tissue edema and inflammatory cell infiltration were compared among the groups. Additionally, proliferating cell nuclear antigen (PCNA) and cluster of differentiation 31 (CD31) immunoexpression levels were evaluated. Furthermore, in biochemical analysis, the tissue levels of vascular endothelial growth factor and (EGF) of the groups were investigated. RESULTS In the phenytoin group, tissue edema and inflammatory cell infiltration were significantly decreased, and PCNA and CD31 immunoexpression levels were more prominent (P < .001) and the tissue EGF levels were significantly higher (P < .01). CONCLUSIONS Topical phenytoin treatment may alter the nasal wound healing after mechanical trauma. The potential beneficial effects of topical phenytoin on nasal mucosa should be investigated by further experimental and human trials. LEVEL OF EVIDENCE NA.
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Affiliation(s)
- Gökçe Şimşek
- Faculty of Medicine, Department of Otolaryngology-Head & Neck Surgery, Kirikkale University Kirikkale, Turkey
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Kim HK, Yeo IK, Li K, Kim BJ, Kim MN, Hong CK. Topical epidermal growth factor for the improvement of acne lesions: a randomized, double-blinded, placebo-controlled, split-face trial. Int J Dermatol 2014; 53:1031-6. [DOI: 10.1111/ijd.12488] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Hyun Kyu Kim
- Department of Dermatology; Chung-Ang University College of Medicine; Seoul Korea
| | - In Kwon Yeo
- Department of Dermatology; Chung-Ang University College of Medicine; Seoul Korea
| | - Kapsok Li
- Department of Dermatology; Chung-Ang University College of Medicine; Seoul Korea
| | - Beom Joon Kim
- Department of Dermatology; Chung-Ang University College of Medicine; Seoul Korea
| | - Myeung Nam Kim
- Department of Dermatology; Chung-Ang University College of Medicine; Seoul Korea
| | - Chang Kwun Hong
- Department of Dermatology; Chung-Ang University College of Medicine; Seoul Korea
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Shin JU, Kang SW, Jeong JJ, Nam KH, Chung WY, Lee JH. Effect of recombinant human epidermal growth factor on cutaneous scar quality in thyroidectomy patients. J DERMATOL TREAT 2014; 26:159-64. [DOI: 10.3109/09546634.2014.906034] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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50
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Xia CY, Yu AX, Qi B, Zhou M, Li ZH, Wang WY. Analysis of blood flow and local expression of angiogenesis‑associated growth factors in infected wounds treated with negative pressure wound therapy. Mol Med Rep 2014; 9:1749-54. [PMID: 24584462 DOI: 10.3892/mmr.2014.1997] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2013] [Accepted: 02/19/2014] [Indexed: 11/06/2022] Open
Abstract
Angiogenesis is involved in the wound healing process. Increased angiogenesis and blood flow constitute a major mechanism of negative pressure wound therapy (NPWT), which has been shown to facilitate the healing of infected wounds. However, the effect on the expression of angiogensis‑related growth factor remains unknown. The goal of the current study was to investigate the angiogenic factor levels prior to and following NPWT in infected wounds. A total of 20 patients with infected wounds treated with NPWT were included in the study. Patients acted as their own control; the postoperative measurements of patients were considered as the experimental group, while preoperative measurements were considered as the controlled group. Blood flow was recorded prior to and during NPWT. A total of 10 angiogensis‑related growth factors were detected using a protein biochip array to analyze the change in protein levels prior to NPWT, and on the third day during NPWT. All wounds were successfully reconstructed by skin grafting or using local flaps following NPWT. NPWT resulted in significantly increased blood flow in the wound. There was a significant increase in vascular endothelial growth factor (VEGF), EGF, platelet‑derived growth factor and angiotesin‑2 following NPWT, while basic fibroblast growth factor decreased significantly. NPWT affects the local expression of angiogenesis‑associated growth factors, which represents another mechanism to explain how NPWT accelerates wound healing.
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Affiliation(s)
- Cheng-Yan Xia
- Department of Micro‑Orthopaedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Ai-Xi Yu
- Department of Micro‑Orthopaedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Baiwen Qi
- Department of Micro‑Orthopaedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Min Zhou
- Department of Micro‑Orthopaedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Zong-Huan Li
- Department of Micro‑Orthopaedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Wei-Yang Wang
- Department of Micro‑Orthopaedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
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