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1
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Workman VL, Giblin AV, Green NH, MacNeil S, Hearnden V. Adipose tissue and adipose-derived stromal cells can reduce skin contraction in an in vitro tissue engineered full thickness skin model. Adipocyte 2025; 14:2473367. [PMID: 40104883 DOI: 10.1080/21623945.2025.2473367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 02/10/2025] [Accepted: 02/17/2025] [Indexed: 03/20/2025] Open
Abstract
Skin contracts during wound healing to facilitate wound closure. In some patients, skin contraction can lead to the formation of skin contractures that limit movement, impair function, and significantly impact well-being. Current treatment options for skin contractures are burdensome for patients, and there is a high risk of recurrence. Autologous fat grafting can improve the structure and function of scarred skin; however, relatively little is known about the effect of fat on skin contraction. In this study, an in vitro tissue-engineered model of human skin was used to test the effects of adipose tissue and adipose-derived stromal cells on skin contraction. Untreated tissue-engineered skin contracted to approximately 60% of the original area over 14 days in culture. The addition of adipose tissue reduced this contraction by 50%. Adipose tissue, which was emulsified or concentrated and high doses of adipose-derived stromal cells (ADSC) were able to inhibit contraction to a similar degree; however, lower doses of ADSC did not show the same effect. In conclusion, the subcutaneous application of adipose tissue has the potential to inhibit skin contraction. This study provides in vitro evidence to support the use of autologous fat grafting to prevent skin contraction in patients most at risk.
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Affiliation(s)
- Victoria L Workman
- Department of Materials Science and Engineering, University of Sheffield, Sheffield, UK
| | - Anna-Victoria Giblin
- Department of Plastic Surgery, Sheffield Teaching Hospitals, NHS Foundation Trust, Sheffield, UK
| | - Nicola H Green
- Department of Materials Science and Engineering, University of Sheffield, Sheffield, UK
- INSIGNEO Institute, University of Sheffield, Sheffield, UK
| | - Sheila MacNeil
- Department of Materials Science and Engineering, University of Sheffield, Sheffield, UK
| | - Vanessa Hearnden
- Department of Materials Science and Engineering, University of Sheffield, Sheffield, UK
- INSIGNEO Institute, University of Sheffield, Sheffield, UK
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2
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Tang SKY, Marshall WF. Physical Forces in Regeneration of Cells and Tissues. Cold Spring Harb Perspect Biol 2025; 17:a041527. [PMID: 38806241 PMCID: PMC11602525 DOI: 10.1101/cshperspect.a041527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/30/2024]
Abstract
The ability to regenerate after the loss of a part is a hallmark of living systems and occurs at both the tissue and organ scales, but also within individual cells. Regeneration entails many processes that are physical and mechanical in nature, including the closure of wounds, the repositioning of material from one place to another, and the restoration of symmetry following perturbations. However, we currently know far more about the genetics and molecular signaling pathways involved in regeneration, and there is a need to investigate the role of physical forces in the process. Here, we will provide an overview of how physical forces may play a role in wound healing and regeneration, in which we compare and contrast regenerative processes at the tissue and cell scales.
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Affiliation(s)
- Sindy K Y Tang
- Department of Mechanical Engineering, Stanford University, Stanford, California 94305-3030, USA
| | - Wallace F Marshall
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158-2517, USA
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3
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Allen RS, Seifert AW. Spiny mice (Acomys) have evolved cellular features to support regenerative healing. Ann N Y Acad Sci 2025; 1544:5-26. [PMID: 39805008 PMCID: PMC11830558 DOI: 10.1111/nyas.15281] [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] [Indexed: 01/16/2025]
Abstract
Spiny mice (Acomys spp.) are warm-blooded (homeothermic) vertebrates whose ability to restore missing tissue through regenerative healing has coincided with the evolution of unique cellular and physiological adaptations across different tissue types. This review seeks to explore how these bizarre rodents deploy unique or altered injury response mechanisms to either enhance tissue repair or fully regenerate excised tissue compared to closely related, scar-forming mammals. First, we examine overall trends in healing Acomys tissues, including the cellular stress response, the ability to activate and maintain cell cycle progression, and the expression of certain features in reproductive adults that are normally associated with embryos. Second, we focus on specific cell types that exhibit precisely regulated proliferation to restore missing tissue. While Acomys utilize many of the same cell types involved in scar formation, these cells exhibit divergent activation profiles during regenerative healing. Considered together, current lines of evidence support sustained deployment of proregenerative pathways in conjunction with transient activation of fibrotic pathways to facilitate regeneration and improve tissue repair in Acomys.
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Affiliation(s)
- Robyn S. Allen
- Department of Biology, University of Kentucky, Lexington, Kentucky, USA
| | - Ashley W. Seifert
- Department of Biology, University of Kentucky, Lexington, Kentucky, USA
- The Spinal Cord and Brain Injury Research Center (SCoBIRC), University of Kentucky, Lexington, Kentucky, USA
- Department of Veterinary Anatomy and Physiology, University of Nairobi, Nairobi, Kenya
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4
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Ghasempour A, Dehghan H, Mahmoudi M, Lavi Arab F. Biomimetic scaffolds loaded with mesenchymal stem cells (MSCs) or MSC-derived exosomes for enhanced wound healing. Stem Cell Res Ther 2024; 15:406. [PMID: 39522032 PMCID: PMC11549779 DOI: 10.1186/s13287-024-04012-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024] Open
Abstract
Since wound healing is one of the most important medical challenges and common dressings have not been able to manage this challenge well today, efforts have been increased to achieve an advanced dressing. Mesenchymal stem cells and exosomes derived from them have shown high potential in healing and regenerating wounds due to their immunomodulatory, anti-inflammatory, immunosuppressive, and high regenerative capacities. However, challenges such as the short life of these cells, the low durability of these cells in the wound area, and the low stability of exosomes derived from them have resulted in limitations in their use for wound healing. Nowadays, different scaffolds are considered suitable biomaterials for wound healing. These scaffolds are made of natural or synthetic polymers and have shown promising potential for an ideal dressing that does not have the disadvantages of common dressings. One of the strategies that has attracted much attention today is using these scaffolds for seeding and delivering MSCs and their exosomes. This combined strategy has shown a high potential in enhancing the shelf life of cells and increasing the stability of exosomes. In this review, the combination of different scaffolds with different MSCs or their exosomes for wound healing has been comprehensively discussed.
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Affiliation(s)
- Alireza Ghasempour
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamideh Dehghan
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Mahmoud Mahmoudi
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fahimeh Lavi Arab
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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5
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Miao C, Zheng Y, Ma Z, Bai L, Hong G, Li L, Li C. Functional and aesthetic results of the Z-shaped and straight lower lip-splitting incision: a randomized clinical trial. Sci Rep 2024; 14:18699. [PMID: 39134573 PMCID: PMC11319339 DOI: 10.1038/s41598-024-63983-z] [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: 10/03/2023] [Accepted: 06/04/2024] [Indexed: 08/15/2024] Open
Abstract
The lip-splitting approach enables excellent access to all areas of the mouth and pharynx to remove tumors; however, traditional lower lip-splitting incisions produce an unsatisfactory scar. To achieve better functional and aesthetic results, we used a Z-shaped incision and compared the functional and aesthetic outcomes of the straight and Z-shaped incisions. Sixty patients who fulfilled the inclusion criteria were randomly divided into two groups and underwent lip-splitting between March 2021 and September 2023. Eventually, 77 patients were reviewed within 6 months and evaluated using the lip function assessment scale, patient and observer scar assessment scale, naïve observer scar assessment scale, and a clinical examination. The Z-shaped incision group performed better in terms of the lip pout movement at 3 months and in the subjective overall opinion, color, irregularity, and pigmentation at 6 months. The Z-shaped incision group had a lower incidence of notched vermilion. In conclusion, Z-shaped lower lip-splitting incisions have better functional and aesthetic outcomes than traditional straight incisions.Trial registration: Public title: Difference between the effect of Z-shaped and vertical incisions of labiobuccal flap on the recovery of lower lip scars. Registration date: 09/03/2021. Registration number: ChiCTR2100044084. Registry URL: http://www.chictr.org.cn .
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Affiliation(s)
- Cheng Miao
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Division for Globalization Initiative, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Ying Zheng
- Chengdu Sixth People's Hospital, Chengdu, Sichuan, China
- West China School of Nursing, Sichuan University, Chengdu, China
| | - Zhongkai Ma
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Lu Bai
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- West China School of Nursing, Sichuan University, Chengdu, China
| | - Guang Hong
- Division for Globalization Initiative, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Longjiang Li
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
- Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
| | - Chunjie Li
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
- Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
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6
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Mohsin F, Javaid S, Tariq M, Mustafa M. Molecular immunological mechanisms of impaired wound healing in diabetic foot ulcers (DFU), current therapeutic strategies and future directions. Int Immunopharmacol 2024; 139:112713. [PMID: 39047451 DOI: 10.1016/j.intimp.2024.112713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 07/02/2024] [Accepted: 07/15/2024] [Indexed: 07/27/2024]
Abstract
Diabetic foot ulcer (DFU) is a foremost cause of amputation in diabetic patients. Consequences of DFU include infections, decline in limb function, hospitalization, amputation, and in severe cases, death. Immune cells including macrophages, regulatory T cells, fibroblasts and other damage repair cells work in sync for effective healing and in establishment of a healthy skin barrier post-injury. Immune dysregulation during the healing of wounds can result in wound chronicity. Hyperglycemic conditions in diabetic patients influence the pathophysiology of wounds by disrupting the immune system as well as promoting neuropathy and ischemic conditions, making them difficult to heal. Chronic wound microenvironment is characterized by increased expression of matrix metalloproteinases, reactive oxygen species as well as pro-inflammatory cytokines, resulting in persistent inflammation and delayed healing. Novel treatment modalities including growth factor therapies, nano formulations, microRNA based treatments and skin grafting approaches have significantly augmented treatment efficiency, demonstrating creditable efficacy in clinical practices. Advancements in local treatments as well as invasive methodologies, for instance formulated wound dressings, stem cell applications and immunomodulatory therapies have been successful in targeting the complex pathophysiology of chronic wounds. This review focuses on elucidating the intricacies of emerging physical and non-physical therapeutic interventions, delving into the realm of advanced wound care and comprehensively summarizing efficacy of evidence-based therapies for DFU currently available.
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Affiliation(s)
- Fatima Mohsin
- KAM School of Life Sciences, Forman Christian College (A Chartered University), Lahore, Pakistan.
| | - Sheza Javaid
- KAM School of Life Sciences, Forman Christian College (A Chartered University), Lahore, Pakistan.
| | - Mishal Tariq
- KAM School of Life Sciences, Forman Christian College (A Chartered University), Lahore, Pakistan.
| | - Muhammad Mustafa
- KAM School of Life Sciences, Forman Christian College (A Chartered University), Lahore, Pakistan.
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7
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Chen J, Zhang T, Liu D, Yang F, Feng Y, Wang A, Wang Y, He X, Luo F, Li J, Tan H, Jiang L. General Semi-Solid Freeze Casting for Uniform Large-Scale Isotropic Porous Scaffolds: An Application for Extensive Oral Mucosal Reconstruction. SMALL METHODS 2024; 8:e2301518. [PMID: 38517272 DOI: 10.1002/smtd.202301518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 02/29/2024] [Indexed: 03/23/2024]
Abstract
Ice-templated porous biomaterials possess transformative potential in regenerative medicine; yet, scaling up ice-templating processes for broader applications-owing to inconsistent pore formation-remains challenging. This study reports an innovative semi-solid freeze-casting technique that draws inspiration from semi-solid metal processing (SSMP) combined with ice cream-production routines. This versatile approach allows for the large-scale assembly of various materials, from polymers to inorganic particles, into isotropic 3D scaffolds featuring uniformly equiaxed pores throughout the centimeter scale. Through (cryo-)electron microscopy, X-ray tomography, and finite element modeling, the structural evolution of ice grains/pores is elucidated, demonstrating how the method increases the initial ice nucleus density by pre-fabricating a semi-frozen slurry, which facilitates a transition from columnar to equiaxed grain structures. For a practical demonstration, as-prepared scaffolds are integrated into a bilayer tissue patch using biodegradable waterborne polyurethane (WPU) for large-scale oral mucosal reconstruction in minipigs. Systematic analyses, including histology and RNA sequencing, prove that the patch modulates the healing process toward near-scarless mucosal remodeling via innate and adaptive immunomodulation and activation of pro-healing genes converging on matrix synthesis and epithelialization. This study not only advances the field of ice-templating fabrication but sets a promising precedent for scaffold-based large-scale tissue regeneration.
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Affiliation(s)
- Jinlin Chen
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Med-X center of materials, Sichuan University, Chengdu, Sichuan, 610065, P. R. China
| | - Tianyu Zhang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, P. R. China
| | - Dan Liu
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, P. R. China
| | - Fan Yang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, P. R. China
| | - Yuan Feng
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Med-X center of materials, Sichuan University, Chengdu, Sichuan, 610065, P. R. China
| | - Ao Wang
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Med-X center of materials, Sichuan University, Chengdu, Sichuan, 610065, P. R. China
| | - Yanchao Wang
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610000, P. R. China
| | - Xueling He
- Editorial Board of Journal of Sichuan University (Medical Sciences), Sichuan University, Chengdu, Sichuan, 610000, P. R. China
| | - Feng Luo
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Med-X center of materials, Sichuan University, Chengdu, Sichuan, 610065, P. R. China
| | - Jiehua Li
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Med-X center of materials, Sichuan University, Chengdu, Sichuan, 610065, P. R. China
| | - Hong Tan
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Med-X center of materials, Sichuan University, Chengdu, Sichuan, 610065, P. R. China
| | - Lu Jiang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, P. R. China
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8
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V Yannas I. Unusual cell-cell cooperative mechanical activity elucidates the process of tissue regeneration. J Biomech 2024; 171:112174. [PMID: 38852483 DOI: 10.1016/j.jbiomech.2024.112174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 05/08/2024] [Accepted: 05/23/2024] [Indexed: 06/11/2024]
Abstract
We have studied wound contraction in three model wounds in animals: excised skin (guinea pig), transected peripheral nerve (rat) and the excised conjunctiva (rabbit). Wound contraction is driven by myofibroblasts bound together by adherens junctions (AJ) that confer cooperative activity to myofibroblasts during wound contraction and synthesis of scar. Grafting with the dermis regeneration template (DRT) cancels cell cooperativity by abolishing AJ connections in myofibroblasts, while also cancelling wound contraction, preventing synthesis of scar and inducing regeneration of excised tissues. The observed definitive prevention of scar synthesis suggests the exploration of DRT scaffolds to regenerate tissues in several other organs and to prevent fibrosis in humans.
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Tabatabaei Hosseini BS, Meadows K, Gabriel V, Hu J, Kim K. Biofabrication of Cellulose-based Hydrogels for Advanced Wound Healing: A Special Emphasis on 3D Bioprinting. Macromol Biosci 2024; 24:e2300376. [PMID: 38031512 DOI: 10.1002/mabi.202300376] [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: 08/17/2023] [Revised: 10/26/2023] [Indexed: 12/01/2023]
Abstract
Even with the current advancements in wound management, addressing most skin injuries and wounds continues to pose a significant obstacle for the healthcare industry. As a result, researchers are now focusing on creating innovative materials utilizing cellulose and its derivatives. Cellulose, the most abundant biopolymer in nature, has unique properties that make it a promising material for wound healing, such as biocompatibility, tunable physiochemical characteristics, accessibility, and low cost. 3D bioprinting technology has enabled the production of cellulose-based wound dressings with complex structures that mimic the extracellular matrix. The inclusion of bioactive molecules such as growth factors offers the ability to aid in promoting wound healing, while cellulose creates an ideal environment for controlled release of these biomolecules and moisture retention. The use of 3D bioprinted cellulose-based wound dressings has potential benefits for managing chronic wounds, burns, and painful wounds by promoting wound healing and reducing the risk of infection. This review provides an up-to-date summary of cellulose-based dressings manufactured by 3D bioprinting techniques by looking into wound healing biology, biofabrication methods, cellulose derivatives, and the existing cellulose bioinks targeted toward wound healing.
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Affiliation(s)
| | - Kieran Meadows
- Department of Biomedical Engineering, University of Calgary, Calgary, Alberta, T2N 1N4, Canada
| | - Vincent Gabriel
- Calgary Firefighters Burn Treatment Centre, Cumming School of Medicine, University of Calgary, Calgary, Alberta, T2N 1N4, Canada
| | - Jinguang Hu
- Department of Petroleum and Chemical Engineering, University of Calgary, Calgary, Alberta, T2N 1N4, Canada
| | - Keekyoung Kim
- Department of Biomedical Engineering, University of Calgary, Calgary, Alberta, T2N 1N4, Canada
- Department of Mechanical and Manufacturing Engineering, University of Calgary, Calgary, Alberta, T2N 1N4, Canada
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10
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Kumar AAW, Lawson-Smith M. Pillar Pain After Minimally Invasive and Standard Open Carpal Tunnel Release: A Systematic Review and Meta-analysis. JOURNAL OF HAND SURGERY GLOBAL ONLINE 2024; 6:212-221. [PMID: 38903842 PMCID: PMC11185895 DOI: 10.1016/j.jhsg.2023.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 12/13/2023] [Indexed: 06/22/2024] Open
Abstract
Purpose Pillar pain is a recognized postoperative complication of carpal tunnel release (CTR). Minimally invasive and alternative surgical techniques can theoretically prevent pillar pain, and the aim of this review was to compare the incidence of pillar pain after standard open CTR and alternative surgical techniques. Methods MEDLINE, Embase, and Scopus databases were thoroughly searched. Randomized controlled trials comparing minimally invasive surgical techniques to standard open CTR were identified. Data, including surgical technique, number of hands, incidence of pillar pain, and follow-up intervals, were extracted. Odds ratios (OR) were expressed as pillar pain incidence in the intervention group relative to standard open CTR. Results There were 12 studies included. No statistically significant differences were noted among endoscopic (OR = 0.53, P = .20), flexor retinaculum lengthening (OR = 1.00, P = 1.00), short incision (OR = 0.41, P = .07) or illuminated knife techniques (OR = 0.18, P = .16). There was a statistically significant decrease in pillar pain after minimally invasive CTR (OR = 0.41, 95% confidence interval 0.20-0.86, I2 = 0%, P = .02) between 3- and 6-months follow-up; however, analyses at all other follow-up periods failed to reach statistical significance. Conclusions Although our findings suggest that standard open CTR may be associated with an increased duration of pillar pain between 3 and 6 months postoperatively, our results suggest that minimally invasive CTR techniques do not affect either the initial development or persistence of pillar pain. Clinical relevance Our results illustrate the natural history of pillar pain with the majority of cases resolving after 6 months, highlighting the utility of symptomatic and conservative treatments and patient education in the management of pillar pain.
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Affiliation(s)
| | - Matthew Lawson-Smith
- The University of Western Australia, Crawley, Western Australia, Australia
- The University of Notre Dame, Fremantle, Western Australia, Australia
- Department of Hand Surgery, Fremantle Hospital, Fremantle, Western Australia, Australia
- Department of Orthopaedic Surgery, Fremantle Hospital, Fremantle, Western Australia, Australia
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11
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Tekinay SH, Tekinay AB. Stem Cells and Nanofibers for Skin Regeneration and Wound Healing. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1470:19-30. [PMID: 38904750 DOI: 10.1007/5584_2024_814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/22/2024]
Abstract
Stem cells have been attractive targets for tissue regeneration due to their inherent ability to differentiate into various specialized cell types; however, efforts for stem cell transplantation for the treatment of degenerated tissues have been hampered by the propensity of some stem cell types to form teratomas and the lessened viability of stem cells after transplantation. These disadvantages can be prevented using tailored extracellular matrix-like materials that can be used as an aid for the transplantation of stem cells. Nanomaterials, in particular nanofibers, have great potential to be used as extracellular matrix-like materials for this purpose. In this article, we will review the use of stem cells and nanofibers for skin regeneration and wound healing.
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Affiliation(s)
- Sarah H Tekinay
- Yildirim Beyazit University, School of Medicine, Ankara, Türkiye
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12
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Dong L, Li X, Leng W, Guo Z, Cai T, Ji X, Xu C, Zhu Z, Lin J. Adipose stem cells in tissue regeneration and repair: From bench to bedside. Regen Ther 2023; 24:547-560. [PMID: 37854632 PMCID: PMC10579872 DOI: 10.1016/j.reth.2023.09.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 09/21/2023] [Accepted: 09/28/2023] [Indexed: 10/20/2023] Open
Abstract
ADSCs are a large number of mesenchymal stem cells in Adipose tissue, which can be applied to tissue engineering. ADSCs have the potential of multi-directional differentiation, and can differentiate into bone tissue, cardiac tissue, urothelial cells, skin tissue, etc. Compared with other mesenchymal stem cells, ADSCs have a multitude of promising advantages, such as abundant number, accessibility in cell culture, stable function, and less immune rejection. There are two main methods to use ADSCs for tissue repair and regeneration. One is to implant the "ADSCs-scaffold composite" into the injured site to promote tissue regeneration. The other is cell-free therapy: using ADSC-exos or ADSC-CM alone to release a large number of miRNAs, cytokines and other bioactive substances to promote tissue regeneration. The tissue regeneration potential of ADSCs is regulated by a variety of cytokines, signaling molecules, and external environment. The differentiation of ADSCs into different tissues is also induced by growth factors, ions, hormones, scaffold materials, physical stimulation, and other factors. The specific mechanisms are complex, and most of the signaling pathways need to be further explored. This article reviews and summarizes the mechanism and clinical application of ADSCs in tissue injury repair so far, and puts forward further problems that need to be solved in this field, hoping to provide directions for further research in this field.
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Affiliation(s)
- Lei Dong
- Department of Urology, Peking University First Hospital, Beijing, 100034, China
- Institute of Urology, Peking University, Beijing, 100034, China
- National Urological Cancer Center, Beijing, 100034, China
- Beijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing, 100034, China
| | - Xiaoyu Li
- Department of Urology, Peking University First Hospital, Beijing, 100034, China
- Institute of Urology, Peking University, Beijing, 100034, China
- National Urological Cancer Center, Beijing, 100034, China
- Beijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing, 100034, China
| | - Wenyuan Leng
- Department of Urology, Peking University First Hospital, Beijing, 100034, China
- Institute of Urology, Peking University, Beijing, 100034, China
- National Urological Cancer Center, Beijing, 100034, China
- Beijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing, 100034, China
| | - Zhenke Guo
- Department of Urology, Peking University First Hospital, Beijing, 100034, China
- Institute of Urology, Peking University, Beijing, 100034, China
- National Urological Cancer Center, Beijing, 100034, China
- Beijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing, 100034, China
| | - Tianyu Cai
- Department of Urology, Peking University First Hospital, Beijing, 100034, China
- Institute of Urology, Peking University, Beijing, 100034, China
- National Urological Cancer Center, Beijing, 100034, China
- Beijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing, 100034, China
| | - Xing Ji
- Department of Urology, Peking University First Hospital, Beijing, 100034, China
- Institute of Urology, Peking University, Beijing, 100034, China
- National Urological Cancer Center, Beijing, 100034, China
- Beijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing, 100034, China
| | - Chunru Xu
- Department of Urology, Peking University First Hospital, Beijing, 100034, China
- Institute of Urology, Peking University, Beijing, 100034, China
- National Urological Cancer Center, Beijing, 100034, China
- Beijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing, 100034, China
| | - Zhenpeng Zhu
- Department of Urology, Peking University First Hospital, Beijing, 100034, China
- Institute of Urology, Peking University, Beijing, 100034, China
- National Urological Cancer Center, Beijing, 100034, China
- Beijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing, 100034, China
| | - Jian Lin
- Department of Urology, Peking University First Hospital, Beijing, 100034, China
- Institute of Urology, Peking University, Beijing, 100034, China
- National Urological Cancer Center, Beijing, 100034, China
- Beijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing, 100034, China
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13
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Zhao Q, Wang J, Qu S, Gong Z, Duan Y, Han L, Wang J, Wang C, Tan J, Yuan Q, Zhang Y. Neuro-Inspired Biomimetic Microreactor for Sensory Recovery and Hair Follicle Neogenesis under Skin Burns. ACS NANO 2023; 17:23115-23131. [PMID: 37934769 DOI: 10.1021/acsnano.3c09107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2023]
Abstract
Deep burns are one of the most severe skin wounds, with typical symptoms being a contradiction between initial severe pain and a subsequent loss of sensation. Although it has long been known that sensory nerves promote skin regeneration and modulate skin function, no proven burn management strategies target sensory nerves. Here, a neuro-inspired biomimetic microreactor is designed based on the immune escape outer membrane of neuroblastoma cells and neural-associated intracellular proteins. The microreactor is constructed on a metal-organic framework (MOF) with a neuroblastoma membrane coating the surface and intracellular proteins loaded inside, called Neuro-MOF. It is loaded into a therapeutic hydrogel and triggers the release of its content proteins upon excitation by near-infrared light. The proteins compensate the skin microenvironment for permanent neurological damage after burns to initiate peripheral nerve regeneration and hair follicle niche formation. In addition, the neuroblastoma cell membrane is displayed on the surface of the Neuro-MOF microreactor, decreasing its immunogenicity and suppressing local inflammation. In a mouse model of deep skin burns, the Neuro-MOF microreactor exhibited significant functional skin regeneration effects, particularly sensory recovery and hair follicle neogenesis.
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Affiliation(s)
- Qin Zhao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430079, China
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
| | - Jinyang Wang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430079, China
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
| | - Shuyuan Qu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430079, China
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
| | - Zijian Gong
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430079, China
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
| | - Yiling Duan
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430079, China
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
| | - Litian Han
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430079, China
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
| | - Jiaolong Wang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430079, China
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
| | - Can Wang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430079, China
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
| | - Jie Tan
- Institute of Chemical Biology and Nanomedicine, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China
| | - Quan Yuan
- Institute of Chemical Biology and Nanomedicine, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China
| | - Yufeng Zhang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430079, China
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
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14
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Wang W, Chen DS, Guo ZD, Yu D, Cao Q, Zhu XW. Artificial dermis combined with skin grafting for the treatment of hand skin and soft tissue defects and exposure of bone and tendon. World J Clin Cases 2023; 11:8003-8012. [DOI: 10.12998/wjcc.v11.i33.8003] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 10/25/2023] [Accepted: 10/30/2023] [Indexed: 11/24/2023] Open
Abstract
BACKGROUND The recovery time of hand wounds is long, which can easily result in chronic and refractory wounds, making the wounds unable to be properly repaired. The treatment cycle is long, the cost is high, and it is prone to recurrence and disability. Double layer artificial dermis combined with autologous skin transplantation has been used to repair hypertrophic scars, deep burn wounds, exposed bone and tendon wounds, and post tumor wounds.
AIM To investigate the therapeutic efficacy of autologous skin graft transplantation in conjunction with double-layer artificial dermis in treating finger skin wounds that are chronically refractory and soft tissue defects that expose bone and tendon.
METHODS Sixty-eight chronic refractory patients with finger skin and soft tissue defects accompanied by bone and tendon exposure who were admitted from July 2021 to June 2022 were included in this study. The observation group was treated with double layer artificial dermis combined with autologous skin graft transplantation (n = 49), while the control group was treated with pedicle skin flap transplantation (n = 17). The treatment status of the two groups of patients was compared, including the time between surgeries and hospital stay. The survival rate of skin grafts/flaps and postoperative wound infections were evaluated using the Vancouver Scar Scale (VSS) for scar scoring at 6 mo after surgery, as well as the sensory injury grading method and two-point resolution test to assess the recovery of skin sensation at 6 mo. The satisfaction of the two groups of patients was also compared.
RESULTS Wound healing time in the observation group was significantly longer than that in the control group (P < 0.05, 27.92 ± 3.25 d vs 19.68 ± 6.91 d); there was no significant difference in the survival rate of skin grafts/flaps between the two patient groups (P > 0.05, 95.1 ± 5.0 vs 96.3 ± 5.6). The interval between two surgeries (20.0 ± 4.3 d) and hospital stay (21.0 ± 10.1 d) in the observation group were both significantly shorter than those in the control group (27.5 ± 9.3 d) and (28.4 ± 17.7 d), respectively (P < 0.05). In comparison to postoperative infection (23.5%) and subcutaneous hematoma (11.8%) in the control group, these were considerably lower at (10.2%) and (6.1%) in the observation group. When comparing the two patient groups at six months post-surgery, the excellent and good rate of sensory recovery (91.8%) was significantly higher in the observation group than in the control group (76.5%) (P < 0.05). There was also no statistically significant difference in two point resolution (P > 0.05). The VSS score in the observation group (2.91 ± 1.36) was significantly lower than that in the control group (5.96 ± 1.51), and group satisfaction was significantly higher (P < 0.05, 90.1 ± 6.3 vs 76.3 ± 5.2).
CONCLUSION The combination of artificial dermis and autologous skin grafting for the treatment of hand tendon exposure wounds has a satisfactory therapeutic effect. It is a safe, effective, and easy to operate treatment method, which is worthy of clinical promotion.
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Affiliation(s)
- Wei Wang
- Department of Operating Room, The First People Hospital of Jiangxia District, Wuhan 430200, Hubei Province, China
| | - Dong-Sheng Chen
- Department of Operating Room, The First People Hospital of Jiangxia District, Wuhan 430200, Hubei Province, China
| | - Zhao-Di Guo
- Department of Hand Surgery, The First People Hospital of Jiangxia District, Wuhan 430200, Hubei Province, China
| | - Dan Yu
- Department of Operating Room, The First People Hospital of Jiangxia District, Wuhan 430200, Hubei Province, China
| | - Qin Cao
- Department of Hand Surgery, The First People Hospital of Jiangxia District, Wuhan 430200, Hubei Province, China
| | - Xiao-Wei Zhu
- Department of Operating Room, The First People Hospital of Jiangxia District, Wuhan 430200, Hubei Province, China
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15
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Wu JM, Yang H, Li Q, Luo TF, Yang P, Huang WC. [Clinical efficacy of local injection of platelet-rich plasma combined with double-layer artificial dermis in treating wounds with exposed tendon on extremity]. ZHONGHUA SHAO SHANG YU CHUANG MIAN XIU FU ZA ZHI 2023; 39:849-856. [PMID: 37805801 DOI: 10.3760/cma.j.cn501225-20230420-00134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 10/09/2023]
Abstract
Objective: To investigate the clinical efficacy of local injection of platelet-rich plasma (PRP) combined with double-layer artificial dermis in treating wounds with exposed tendon on extremity. Methods: A retrospective observational study was conducted. From December 2017 to October 2022, 16 patients were admitted to Department of Orthopaedic Trauma of the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, and 32 patients were admitted to Department of Burns and Plastic Surgery of Guiyang Steel Factory Staff Hospital. All the patients had wounds with exposed tendon on extremity caused by various reasons and met the inclusion criteria. There were 39 males and 9 females, aged 26 to 58 years. The patients were divided into PRP alone group, artificial dermis alone group, and PRP+artificial dermis group, with 16 patients in each group. The wounds were treated with autologous PRP, double-layer artificial dermis, or thei combination of autologous PRP and double-layer artificial dermis, followed by autologous split-thickness scalp grafting after good growth of granulation tissue. On the 7th day after the secondary surgery, the autograft survival was observed, and the survival rate was calculated. The wound healing time and length of hospital stay of patients were recorded. At 3 and 6 months after wound healing, the Vancouver scar scale (VSS) was used to score the pigmentation, height, vascularity, and pliability of scars, and the total score was calculated. Adverse reactions during the entire treatment process were recorded. Data were statistically analyzed with chi-square test, Fisher's exact probability test, one-way analysis of variance, least significant difference test, Kruskal-Wallis H test, Nemenyi test, and Bonferroni correction. Results: On the 7th day after the secondary surgery, there was no statistically significant difference in the autograft survival rate of patients among PRP alone group, artificial dermis alone group, and PRP+artificial dermis group (P>0.05). The wound healing time and length of hospital stay of patients in PRP+artificial dermis group were (20.1±3.0) and (24±4) d, respectively, which were significantly shorter than (24.4±5.5) and (30±8) d in PRP alone group (P<0.05) and (24.8±4.9) and (32±8) d in artificial dermis alone group (P<0.05). At 3 and 6 months after wound healing, the pliability scores of patients in PRP+artificial dermis group were significantly lower than those in PRP alone group (with Z values of 12.91 and 15.69, respectively, P<0.05) and artificial dermis alone group (with Z values of 12.50 and 12.91, respectively, P<0.05). There were no statistically significant differences in pigmentation, vascularity, height scores, and total score of scar of patients among the three groups (P>0.05). In artificial dermis alone group, one patient experienced partial liquefaction and detachment of the double-layer artificial dermis due to local infection of Staphylococcus epidermidis, which received wound dressing change, second artificial dermis transplantation, and subsequent treatment as before. No adverse reactions occurred in the remaining patients during the whole treatment process. Conclusions: Local injection of PRP combined with double-layer artificial dermis is effective in treating wounds with exposed tendon on extremity, which can not only significantly shorten wound healing time and length of hospital stay, but also improve scar pliability after wound healing to some extent in the long term. It is a clinically valuable treatment technique that is worth promoting and applying.
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Affiliation(s)
- J M Wu
- Department of Burns and Plastic Surgery, the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, China Department of Burns and Plastic Surgery, Guiyang Steel Factory Staff Hospital, Guiyang 550005, China
| | - H Yang
- Department of Burns and Plastic Surgery, Guiyang Steel Factory Staff Hospital, Guiyang 550005, China
| | - Q Li
- Department of Burns and Plastic Surgery, Guiyang Steel Factory Staff Hospital, Guiyang 550005, China
| | - T F Luo
- Department of Burns and Plastic Surgery, Guiyang Steel Factory Staff Hospital, Guiyang 550005, China
| | - P Yang
- Department of Orthopaedic Trauma, the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, China
| | - W C Huang
- Department of Orthopaedic Trauma, the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, China
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16
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Yang T, Hei R, Li X, Ma T, Shen Y, Liu C, He W, Zhu L, Gu Y, Hu Y, Wei W, Shen Y. The role of NPY2R/NFATc1/DYRK1A regulatory axis in sebaceous glands for sebum synthesis. Cell Mol Biol Lett 2023; 28:60. [PMID: 37501148 PMCID: PMC10375735 DOI: 10.1186/s11658-023-00467-4] [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: 04/27/2023] [Accepted: 06/15/2023] [Indexed: 07/29/2023] Open
Abstract
BACKGROUND Sebaceous glands (SGs) synthesize and secret sebum to protect and moisturize the dermal system via the complicated endocrine modulation. Dysfunction of SG are usually implicated in a number of dermal and inflammatory diseases. However, the molecular mechanism behind the differentiation, development and proliferation of SGs is far away to fully understand. METHODS Herein, the rat volar and mammary tissues with abundant SGs from female SD rats with (post-natal day (PND)-35) and without puberty onset (PND-25) were arrested, and conducted RNA sequencing. The protein complex of Neuropeptide Y receptor Y2 (NPY2R)/NPY5R/Nuclear factor of activated T cells 1 (NFATc1) was performed by immunoprecipitation, mass spectrum and gel filtration. Genome-wide occupancy of NFATc1 was measured by chromatin immunoprecipitation sequencing. Target proteins' expression and localization was detected by western blot and immunofluorescence. RESULTS NPY2R gene was significantly up-regulated in volar and mammary SGs of PND-25. A special protein complex of NPY2R/NPY5R/NFATc1 in PND-25. NFATc1 was dephosphorylated and activated, then localized into nucleus to exert as a transcription factor in volar SGs of PND-35. NFATc1 was especially binding at enhancer regions to facilitate the distal SG and sebum related genes' transcription. Dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) contributed to NFATc1 phosphorylation in PND-25, and inactivated of DYRK1A resulted in NFATc1 dephosphorylation and nuclear localization in PND-35. CONCLUSIONS Our findings unmask the new role of NPY2R/NFATc1/DYRK1A in pubertal SG, and are of benefit to advanced understanding the molecular mechanism of SGs' function after puberty, and provide some theoretical basis for the treatment of acne vulgaris from the perspective of hormone regulation.
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Affiliation(s)
- Tao Yang
- Department of Medical Cosmetology, Suzhou Ninth People's Hospital, Suzhou, 215200, Jiangsu, China
| | - Renyi Hei
- Department of Otolaryngology-Head and Neck Surgery, General Hospital of Shenyang Military Area Command, Shenyang, 110016, Liaoning, China
| | - Xiaosong Li
- Department of Anorectal Surgery, Suzhou Ninth People's Hospital, Suzhou, 215200, Jiangsu, China
| | - Tianhua Ma
- Graduate School of Soochow University, Suzhou, 215031, Jiangsu, China
| | - Yifen Shen
- Central Laboratory, Suzhou Ninth People's Hospital, 2666, Ludang Road, Suzhou, 215200, Jiangsu, China
| | - Chao Liu
- Central Laboratory, Suzhou Ninth People's Hospital, 2666, Ludang Road, Suzhou, 215200, Jiangsu, China
| | - Wen He
- Central Laboratory, Suzhou Ninth People's Hospital, 2666, Ludang Road, Suzhou, 215200, Jiangsu, China
| | - Lin Zhu
- Central Laboratory, Suzhou Ninth People's Hospital, 2666, Ludang Road, Suzhou, 215200, Jiangsu, China
| | - Yongchun Gu
- Central Laboratory, Suzhou Ninth People's Hospital, 2666, Ludang Road, Suzhou, 215200, Jiangsu, China
| | - Yanping Hu
- Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, 450008, Henan, China
| | - Wenbin Wei
- Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, No. 639 Zhizaoju Road, Huangpu District, Shanghai, 200013, China.
| | - Yihang Shen
- Central Laboratory, Suzhou Ninth People's Hospital, 2666, Ludang Road, Suzhou, 215200, Jiangsu, China.
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17
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Zhang GK, Ren J, Li JP, Wang DX, Wang SN, Shi LY, Li CY. Injectable hydrogel made from antler mesenchyme matrix for regenerative wound healing via creating a fetal-like niche. World J Stem Cells 2023; 15:768-780. [PMID: 37545751 PMCID: PMC10401419 DOI: 10.4252/wjsc.v15.i7.768] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 06/09/2023] [Accepted: 07/11/2023] [Indexed: 07/25/2023] Open
Abstract
BACKGROUND Scar formation and loss of cutaneous appendages are the greatest challenges in cutaneous wound healing. Previous studies have indicated that antler reserve mesenchyme (RM) cells and their conditioned medium improved regenerative wound healing with partial recovery of cutaneous appendages.
AIM To develop hydrogels from the antler RM matrix (HARM) and evaluate the effect on wound healing.
METHODS We prepared the hydrogels from the HARM via enzymatic solubilization with pepsin. Then we investigated the therapeutic effects of HARM on a full-thickness cutaneous wound healing rat model using both local injections surrounding the wound and topical wound application.
RESULTS The results showed that HARM accelerated wound healing rate and reduced scar formation. Also, HARM stimulated the regeneration of cutaneous appendages and blood vessels, and reduced collagen fiber aggregation. Further study showed that these functions might be achieved via creating a fetal-like niche at the wound site. The levels of fetal wound healing-related genes, including Collagen III and TGFβ3 treated with HARM were all increased, while the expression levels of Collagen I, TGFβ1, and Engrailed 1 were decreased in the healing. Moreover, the number of stem cells was increased in the fetal-like niche created by HARM, which may contribute to the regeneration of cutaneous appendages.
CONCLUSION Overall, we successfully developed an injectable hydrogel made from antler RM matrix for the regenerative repair of full-thickness cutaneous wounds. We uncovered the molecular mechanism of the hydrogels in promoting regenerative wound healing, and thus pave the way for HARM to be developed for the clinic use.
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Affiliation(s)
- Guo-Kun Zhang
- Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Changchun 130600, Jilin Province, China
| | - Jing Ren
- Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Changchun 130600, Jilin Province, China
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, Jilin Province, China
| | - Ji-Ping Li
- Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Changchun 130600, Jilin Province, China
| | - Dong-Xu Wang
- Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Changchun 130600, Jilin Province, China
| | - Sheng-Nan Wang
- Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Changchun 130600, Jilin Province, China
| | - Li-Yan Shi
- China-Japan Union Hospital, Jilin University, Changchun 130033, Jilin Province, China
| | - Chun-Yi Li
- Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Changchun 130600, Jilin Province, China
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, Jilin Province, China
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18
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Iacopetti I, Perazzi A, Patruno M, Contiero B, Carolo A, Martinello T, Melotti L. Assessment of the quality of the healing process in experimentally induced skin lesions treated with autologous platelet concentrate associated or unassociated with allogeneic mesenchymal stem cells: preliminary results in a large animal model. Front Vet Sci 2023; 10:1219833. [PMID: 37559892 PMCID: PMC10407250 DOI: 10.3389/fvets.2023.1219833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 07/13/2023] [Indexed: 08/11/2023] Open
Abstract
Regenerative medicine for the treatment of skin lesions is an innovative and rapidly developing field that aims to promote wound healing and restore the skin to its original condition before injury. Over the years, different topical treatments have been evaluated to improve skin wound healing and, among them, mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) have shown promising results for this purpose. This study sought to evaluate the quality of the healing process in experimentally induced full-thickness skin lesions treated with PRP associated or unassociated with MSCs in a sheep second intention wound healing model. After having surgically created full-thickness wounds on the back of three sheep, the wound healing process was assessed by performing clinical evaluations, histopathological examinations, and molecular analysis. Treated wounds showed a reduction of inflammation and contraction along with an increased re-epithelialization rate and better maturation of the granulation tissue compared to untreated lesions. In particular, the combined treatment regulated the expression of collagen types I and III resulting in a proper resolution of the granulation tissue contrary to what was observed in untreated wounds; moreover, it led to a better maturation and organization of skin adnexa and collagen fibers in the repaired skin compared to untreated and PRP-treated wounds. Overall, both treatments improved the wound healing process compared to untreated wounds. Wounds treated with PRP and MSCs showed a healing progression that qualitatively resembles a restitutio ad integrum of the repaired skin, showing features typical of a mature healthy dermis.
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Affiliation(s)
- Ilaria Iacopetti
- Department of Animal Medicine, Production and Health, University of Padua, Padova, Italy
| | - Anna Perazzi
- Department of Animal Medicine, Production and Health, University of Padua, Padova, Italy
| | - Marco Patruno
- Department of Comparative Biomedicine and Food Science, University of Padua, Padova, Italy
| | - Barbara Contiero
- Department of Animal Medicine, Production and Health, University of Padua, Padova, Italy
| | - Anna Carolo
- Department of Comparative Biomedicine and Food Science, University of Padua, Padova, Italy
| | | | - Luca Melotti
- Department of Comparative Biomedicine and Food Science, University of Padua, Padova, Italy
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Borbolla-Jiménez FV, Peña-Corona SI, Farah SJ, Jiménez-Valdés MT, Pineda-Pérez E, Romero-Montero A, Del Prado-Audelo ML, Bernal-Chávez SA, Magaña JJ, Leyva-Gómez G. Films for Wound Healing Fabricated Using a Solvent Casting Technique. Pharmaceutics 2023; 15:1914. [PMID: 37514100 PMCID: PMC10384592 DOI: 10.3390/pharmaceutics15071914] [Citation(s) in RCA: 43] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 06/10/2023] [Accepted: 06/27/2023] [Indexed: 07/30/2023] Open
Abstract
Wound healing is a complex process that involves restoring the structure of damaged tissues through four phases: hemostasis, inflammation, proliferation, and remodeling. Wound dressings are the most common treatment used to cover wounds, reduce infection risk and the loss of physiological fluids, and enhance wound healing. Despite there being several types of wound dressings based on different materials and fabricated through various techniques, polymeric films have been widely employed due to their biocompatibility and low immunogenicity. Furthermore, they are non-invasive, easy to apply, allow gas exchange, and can be transparent. Among different methods for designing polymeric films, solvent casting represents a reliable, preferable, and highly used technique due to its easygoing and relatively low-cost procedure compared to sophisticated methods such as spin coating, microfluidic spinning, or 3D printing. Therefore, this review focuses on the polymeric dressings obtained using this technique, emphasizing the critical manufacturing factors related to pharmaceuticals, specifically discussing the formulation variables necessary to create wound dressings that demonstrate effective performance.
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Affiliation(s)
- Fabiola V Borbolla-Jiménez
- Laboratorio de Medicina Genómica, Departamento de Genómica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México 14389, Mexico
- Tecnologico de Monterrey, Campus Ciudad de México, Ciudad de México 14380, Mexico
| | - Sheila I Peña-Corona
- Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico
| | - Sonia J Farah
- Laboratorio de Medicina Genómica, Departamento de Genómica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México 14389, Mexico
- Tecnologico de Monterrey, Campus Ciudad de México, Ciudad de México 14380, Mexico
| | - María Teresa Jiménez-Valdés
- Laboratorio de Medicina Genómica, Departamento de Genómica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México 14389, Mexico
- Tecnologico de Monterrey, Campus Ciudad de México, Ciudad de México 14380, Mexico
| | - Emiliano Pineda-Pérez
- Laboratorio de Medicina Genómica, Departamento de Genómica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México 14389, Mexico
- Tecnologico de Monterrey, Campus Ciudad de México, Ciudad de México 14380, Mexico
| | - Alejandra Romero-Montero
- Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico
| | | | - Sergio Alberto Bernal-Chávez
- Departamento de Ciencias Químico-Biológicas, Universidad de las Américas Puebla, Ex-Hda. de Sta. Catarina Mártir, Cholula 72820, Puebla, Mexico
| | - Jonathan J Magaña
- Laboratorio de Medicina Genómica, Departamento de Genómica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México 14389, Mexico
- Tecnologico de Monterrey, Campus Ciudad de México, Ciudad de México 14380, Mexico
| | - Gerardo Leyva-Gómez
- Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico
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20
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Gao S, Zhou R, Gao W. Repairing Small Facial Soft Tissue Defects by Tissue Regeneration in Asians. J Craniofac Surg 2023; 34:708-711. [PMID: 36260432 DOI: 10.1097/scs.0000000000008812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2023] Open
Abstract
BACKGROUND A variety of options are available to repair the small facial soft tissue defects after surgical removal of cutaneous tumor, including direct suture, skin grafts, local, regional or free flaps. However, tissue regeneration is another option for repairing facial defects. This study proposes the clinical application of the principle of tissue regeneration priority in small defects (diameter <1.3 cm) of facial soft tissue. METHODS A retrospective study of 33 patients whose facial defects were repaired by tissue regeneration healing in situ from January 2019 to January 2022. In this group, the facial soft tissue defects were treated with wound moist theory in order to promote wound regeneration. RESULT All patients underwent 1 month follow-up at least and the longest follow-up time was 6 months. Hundred percent of the patients were satisfied with their cosmetic outcome. Only some patients formed small depression scars after surgery, the appearance of which were similar to acne scar. In this situation, re-resection and laser treatment could be used as complementary procedures. However, no patient underwent the secondary treatments including laser and re-resection. CONCLUSION Healing by tissue regeneration is an effective option for the facial defects in Asians. For most of the small soft tissue defects of the face, tissue regeneration in situ can achieve satisfactory effects. More importantly, it has the advantages of simple operation and fewer complications.
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Affiliation(s)
- Shenzhen Gao
- Department of Plastic and Cosmetic Surgery, The Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
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21
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Singh SK, Dwivedi SD, Yadav K, Shah K, Chauhan NS, Pradhan M, Singh MR, Singh D. Novel Biotherapeutics Targeting Biomolecular and Cellular Approaches in Diabetic Wound Healing. Biomedicines 2023; 11:biomedicines11020613. [PMID: 36831151 PMCID: PMC9952895 DOI: 10.3390/biomedicines11020613] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 02/12/2023] [Accepted: 02/15/2023] [Indexed: 02/22/2023] Open
Abstract
Wound healing responses play a major role in chronic inflammation, which affects millions of people around the world. One of the daunting tasks of creating a wound-healing drug is finding equilibrium in the inflammatory cascade. In this study, the molecular and cellular mechanisms to regulate wound healing are explained, and recent research is addressed that demonstrates the molecular and cellular events during diabetic wound healing. Moreover, a range of factors or agents that facilitate wound healing have also been investigated as possible targets for successful treatment. It also summarises the various advances in research findings that have revealed promising molecular targets in the fields of therapy and diagnosis of cellular physiology and pathology of wound healing, such as neuropeptides, substance P, T cell immune response cDNA 7, miRNA, and treprostinil growth factors such as fibroblast growth factor, including thymosin beta 4, and immunomodulators as major therapeutic targets.
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Affiliation(s)
- Suraj Kumar Singh
- University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur 492010, Chhattisgarh, India
| | - Shradha Devi Dwivedi
- University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur 492010, Chhattisgarh, India
| | - Krishna Yadav
- Raipur Institute of Pharmaceutical Educations and Research, Sarona, Raipur 492010, Chhattisgarh, India
| | - Kamal Shah
- Institute of Pharmaceutical Research, GLA University, Mathura 281406, Uttar Pradesh, India
| | | | - Madhulika Pradhan
- Gracious College of Pharmacy Abhanpur Raipur, Village-Belbhata, Taluka, Abhanpur 493661, Chhattisgarh, India
| | - Manju Rawat Singh
- University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur 492010, Chhattisgarh, India
| | - Deependra Singh
- University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur 492010, Chhattisgarh, India
- Correspondence:
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22
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Fascia Layer-A Novel Target for the Application of Biomaterials in Skin Wound Healing. Int J Mol Sci 2023; 24:ijms24032936. [PMID: 36769257 PMCID: PMC9917695 DOI: 10.3390/ijms24032936] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 01/28/2023] [Accepted: 01/31/2023] [Indexed: 02/05/2023] Open
Abstract
As the first barrier of the human body, the skin has been of great concern for its wound healing and regeneration. The healing of large, refractory wounds is difficult to be repaired by cell proliferation at the wound edges and usually requires manual intervention for treatment. Therefore, therapeutic tools such as stem cells, biomaterials, and cytokines have been applied to the treatment of skin wounds. Skin microenvironment modulation is a key technology to promote wound repair and skin regeneration. In recent years, a series of novel bioactive materials that modulate the microenvironment and cell behavior have been developed, showing the ability to efficiently facilitate wound repair and skin attachment regeneration. Meanwhile, our lab found that the fascial layer has an indispensable role in wound healing and repair, and this review summarizes the research progress of related bioactive materials and their role in wound healing.
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23
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Linntam D, Klett A. Laissez-faire Technique in Periocular Reconstructive Surgery following Tumour Resection. Klin Monbl Augenheilkd 2023; 240:39-43. [PMID: 36368664 DOI: 10.1055/a-1947-5458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
The laissez-faire technique, although not widely used by oculoplastic surgeons, is a valuable option in the reconstruction of periocular defects following tumour resection. In the authors' experience, the most suitable location is the medial canthal area. Primary surgery is often simpler and better tolerated by the patient compared with alternative, more complex surgical procedures. The final functional and cosmetic outcome is highly dependent on patient selection and for an excellent result, certain modifications in surgical technique and additional manipulations in the early postoperative period must be considered. The technique is not usually the first choice, due to fear of a prolonged and complicated wound healing period. The unpredictability of the results may also be of concern to oculoplastic surgeons. This case series illustrates some modifications of surgery and postoperative care that can help optimise the outcome and reduce postoperative complications. As wound healing and scarring are influenced by contraction in the wound bed, tension guiding sutures are a valuable adjunct to laissez-faire techniques. They improve the predictability of the result after healing, and this is important primarily in reducing the risk of cicatricial ectropium, but also in the cosmetic result. Although there is a risk of infection with any open wound, in general, thorough patient education usually suffices to avoid postoperative complications. Appropriate wound care in the laissez-faire technique is fairly simple and easily achievable.
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Affiliation(s)
- Delis Linntam
- Eye Clinic, East Tallinn Central Hospital, Tallinn, Estonia
| | - Artur Klett
- Eye Clinic, East Tallinn Central Hospital, Tallinn, Estonia
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24
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Hosseini M, Dalley AJ, Shafiee A. Convergence of Biofabrication Technologies and Cell Therapies for Wound Healing. Pharmaceutics 2022; 14:pharmaceutics14122749. [PMID: 36559242 PMCID: PMC9785239 DOI: 10.3390/pharmaceutics14122749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 12/01/2022] [Accepted: 12/04/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Cell therapy holds great promise for cutaneous wound treatment but presents practical and clinical challenges, mainly related to the lack of a supportive and inductive microenvironment for cells after transplantation. Main: This review delineates the challenges and opportunities in cell therapies for acute and chronic wounds and highlights the contribution of biofabricated matrices to skin reconstruction. The complexity of the wound healing process necessitates the development of matrices with properties comparable to the extracellular matrix in the skin for their structure and composition. Over recent years, emerging biofabrication technologies have shown a capacity for creating complex matrices. In cell therapy, multifunctional material-based matrices have benefits in enhancing cell retention and survival, reducing healing time, and preventing infection and cell transplant rejection. Additionally, they can improve the efficacy of cell therapy, owing to their potential to modulate cell behaviors and regulate spatiotemporal patterns of wound healing. CONCLUSION The ongoing development of biofabrication technologies promises to deliver material-based matrices that are rich in supportive, phenotype patterning cell niches and are robust enough to provide physical protection for the cells during implantation.
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Affiliation(s)
- Motaharesadat Hosseini
- School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology, Brisbane, QLD 4059, Australia
- ARC Industrial Transformation Training Centre for Multiscale 3D Imaging, Modelling and Manufacturing (M3D), Queensland University of Technology, Brisbane, QLD 4059, Australia
| | - Andrew J. Dalley
- Herston Biofabrication Institute, Metro North Hospital and Health Service, Brisbane, QLD 4029, Australia
- Royal Brisbane and Women’s Hospital, Metro North Hospital and Health Service, Brisbane, QLD 4029, Australia
| | - Abbas Shafiee
- Herston Biofabrication Institute, Metro North Hospital and Health Service, Brisbane, QLD 4029, Australia
- Royal Brisbane and Women’s Hospital, Metro North Hospital and Health Service, Brisbane, QLD 4029, Australia
- Frazer Institute, Translational Research Institute, The University of Queensland, Brisbane, QLD 4102, Australia
- Correspondence: or
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25
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Miyazawa M, Aikawa M, Takashima J, Kobayashi H, Ohnishi S, Ikada Y. Pitfalls and promises of bile duct alternatives: A narrative review. World J Gastroenterol 2022; 28:5707-5722. [PMID: 36338889 PMCID: PMC9627420 DOI: 10.3748/wjg.v28.i39.5707] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 08/18/2022] [Accepted: 09/23/2022] [Indexed: 02/06/2023] Open
Abstract
Biliodigestive anastomosis between the extrahepatic bile duct and the intestine for bile duct disease is a gastrointestinal reconstruction that abolishes duodenal papilla function and frequently causes retrograde cholangitis. This chronic inflammation can cause liver dysfunction, liver abscess, and even bile duct cancer. Although research has been conducted for over 100 years to directly repair bile duct defects with alternatives, no bile duct substitute (BDS) has been developed. This narrative review confirms our understanding of why bile duct alternatives have not been developed and explains the clinical applicability of BDSs in the near future. We searched the PubMed electronic database to identify studies conducted to develop BDSs until December 2021 and identified studies in English. Two independent reviewers reviewed studies on large animals with 8 or more cases. Four types of BDSs prevail: Autologous tissue, non-bioabsorbable material, bioabsorbable material, and others (decellularized tissue, 3D-printed structures, etc.). In most studies, BDSs failed due to obstruction of the lumen or stenosis of the anastomosis with the native bile duct. BDS has not been developed primarily because control of bile duct wound healing and regeneration has not been elucidated. A BDS expected to be clinically applied in the near future incorporates a bioabsorbable material that allows for regeneration of the bile duct outside the BDS.
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Affiliation(s)
- Mitsuo Miyazawa
- Department of Surgery, Teikyo University Mizonokuch Hospital, Kanagawa 213-8507, Japan
| | - Masayasu Aikawa
- Department of Surgery, Saitama Medical University International Medical Center, Saitama 350-1298, Japan
| | - Junpei Takashima
- Department of Surgery, Teikyo University Mizonokuch Hospital, Kanagawa 213-8507, Japan
| | - Hirotoshi Kobayashi
- Department of Surgery, Teikyo University Mizonokuch Hospital, Kanagawa 213-8507, Japan
| | - Shunsuke Ohnishi
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Yoshito Ikada
- Department of Bioenvironmental Medicine, Nara Medical University, Nara 634-8521, Japan
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Aderibigbe BA. Hybrid-Based Wound Dressings: Combination of Synthetic and Biopolymers. Polymers (Basel) 2022; 14:3806. [PMID: 36145951 PMCID: PMC9502880 DOI: 10.3390/polym14183806] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/03/2022] [Accepted: 09/05/2022] [Indexed: 11/16/2022] Open
Abstract
Most commercialized wound dressings are polymer-based. Synthetic and natural polymers have been utilized widely for the development of wound dressings. However, the use of natural polymers is limited by their poor mechanical properties, resulting in their combination with synthetic polymers and other materials to enhance their mechanical properties. Natural polymers are mostly affordable, biocompatible, and biodegradable with promising antimicrobial activity. They have been further tailored into unique hybrid wound dressings when combined with synthetic polymers and selected biomaterials. Some important features required in an ideal wound dressing include the capability to prevent bacteria invasion, reduce odor, absorb exudates, be comfortable, facilitate easy application and removal as well as frequent changing, prevent further skin tear and irritation when applied or removed, and provide a moist environment and soothing effect, be permeable to gases, etc. The efficacy of polymers in the design of wound dressings cannot be overemphasized. This review article reports the efficacy of wound dressings prepared from a combination of synthetic and natural polymers.
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27
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Hosseini M, Brown J, Khosrotehrani K, Bayat A, Shafiee A. Skin biomechanics: a potential therapeutic intervention target to reduce scarring. BURNS & TRAUMA 2022; 10:tkac036. [PMID: 36017082 PMCID: PMC9398863 DOI: 10.1093/burnst/tkac036] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 04/27/2022] [Indexed: 12/19/2022]
Abstract
Pathological scarring imposes a major clinical and social burden worldwide. Human cutaneous wounds are responsive to mechanical forces and convert mechanical cues to biochemical signals that eventually promote scarring. To understand the mechanotransduction pathways in cutaneous scarring and develop new mechanotherapy approaches to achieve optimal scarring, the current study highlights the mechanical behavior of unwounded and scarred skin as well as intra- and extracellular mechanisms behind keloid and hypertrophic scars. Additionally, the therapeutic interventions that promote optimal scar healing by mechanical means at the molecular, cellular or tissue level are extensively reviewed. The current literature highlights the significant role of fibroblasts in wound contraction and scar formation via differentiation into myofibroblasts. Thus, understanding myofibroblasts and their responses to mechanical loading allows the development of new scar therapeutics. A review of the current clinical and preclinical studies suggests that existing treatment strategies only reduce scarring on a small scale after wound closure and result in poor functional and aesthetic outcomes. Therefore, the perspective of mechanotherapies needs to consider the application of both mechanical forces and biochemical cues to achieve optimal scarring. Moreover, early intervention is critical in wound management; thus, mechanoregulation should be conducted during the healing process to avoid scar maturation. Future studies should either consider combining mechanical loading (pressure) therapies with tension offloading approaches for scar management or developing more effective early therapies based on contraction-blocking biomaterials for the prevention of pathological scarring.
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Affiliation(s)
- Motaharesadat Hosseini
- Centre for Biomedical Technologies, School of Mechanical, Medical and Process Engineering (MMPE), Faculty of Engineering, Queensland University of Technology, Brisbane, QLD 4059, Australia
| | - Jason Brown
- Herston Biofabrication Institute, Metro North Hospital and Health Service, Brisbane, QLD 4029, Australia
| | - Kiarash Khosrotehrani
- The University of Queensland Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, QLD 4102, Australia
| | - Ardeshir Bayat
- Centre for Dermatology Research, NIHR Manchester Biomedical Research Centre, Stopford Building, University of Manchester, Oxford Road, Manchester, M13 9PT, England, UK
| | - Abbas Shafiee
- Herston Biofabrication Institute, Metro North Hospital and Health Service, Brisbane, QLD 4029, Australia
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28
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Brown SJ, Surti F, Sibbons P, Hook L. Wound healing properties of a fibrin-based dermal replacement scaffold. Biomed Phys Eng Express 2021; 8. [PMID: 34883468 DOI: 10.1088/2057-1976/ac4176] [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] [Received: 09/08/2021] [Accepted: 12/09/2021] [Indexed: 11/11/2022]
Abstract
When serious cutaneous injury occurs, the innate wound healing process attempts to restore the skin's appearance and function. Wound healing outcome is affected by factors such as contraction, revascularisation, regeneration versus fibrosis and re-epithelialisation and is also strongly influenced by the pattern and extent of damage to the dermal layer. Dermal replacement scaffolds have been designed to substitute for lost tissue, provide a structure to promote dermal regeneration, and aid skin grafting, resulting in a superior healing outcome. In this study the wound healing properties of a novel fibrin-alginate dermal scaffold were assessed in the porcine wound healing model and also compared to two widely used dermal scaffolds and grafting alone. The fibrin-alginate scaffold, unlike the other scaffolds tested, is not used in combination with an overlying skin graft. Fibrin scaffold treated wounds showed increased, sustained superficial blood flow and reduced contraction during early healing while showing comparable wound closure, re-epithelialisation and final wound outcome to other treatments. The increase in early wound vascularisation coupled with a decrease in contraction and no requirement for a skin graft suggest that the fibrin-based scaffold could provide an effective, distinctive treatment option to improve healing outcomes in human patients.
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Affiliation(s)
- Stuart J Brown
- Centre for Stem Cells and Regenerative Medicine, 28th Floor Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, United Kingdom.,RAFT Institute, 475 Salisbury House, London Wall, London EC2M 5QQ, United Kingdom
| | - Farhana Surti
- The Griffin Institute , Northwick Park and St Mark's Hospital, Y Block, Watford Road, Harrow, Middlesex, HA1 3UJ, United Kingdom
| | - Paul Sibbons
- The Griffin Institute , Northwick Park and St Mark's Hospital, Y Block, Watford Road, Harrow, Middlesex, HA1 3UJ, United Kingdom
| | - Lilian Hook
- Smart Matrix Ltd, 3rd Floor, 207 Regent Street , London W1B 3HH, United Kingdom
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29
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Lyu GZ, Zhao P. [New bioactive materials for promoting wound repair and skin regeneration]. ZHONGHUA SHAO SHANG ZA ZHI = ZHONGHUA SHAOSHANG ZAZHI = CHINESE JOURNAL OF BURNS 2021; 37:1105-1109. [PMID: 34839605 PMCID: PMC11917273 DOI: 10.3760/cma.j.cn501120-20211029-00373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
The modulation of microenvironment is a key technology towards promoting wound repair and skin regeneration. In recent years, a series of new bioactive materials that modulate the microenvironment and cell behaviors have been developed, demonstrating highly efficient capability of inducing wound repair and skin appendage regeneration. This article summarizes the research development of related new bioactive materials and their mechanisms of action.
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Affiliation(s)
- G Z Lyu
- Engineering Research Center of the Ministry of Education for Wound Repair Technology, Treatment Center of Burns and Trauma, the Affiliated Hospital of Jiangnan University, Wuxi 214122, China
| | - P Zhao
- Engineering Research Center of the Ministry of Education for Wound Repair Technology, Treatment Center of Burns and Trauma, the Affiliated Hospital of Jiangnan University, Wuxi 214122, China
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30
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Sohutskay DO, Buganza Tepole A, Voytik-Harbin SL. Mechanobiological wound model for improved design and evaluation of collagen dermal replacement scaffolds. Acta Biomater 2021; 135:368-382. [PMID: 34390846 DOI: 10.1016/j.actbio.2021.08.007] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 08/03/2021] [Accepted: 08/05/2021] [Indexed: 10/20/2022]
Abstract
Skin wounds are among the most common and costly medical problems experienced. Despite the myriad of treatment options, such wounds continue to lead to displeasing cosmetic outcomes and also carry a high burden of loss-of-function, scarring, contraction, or nonhealing. As a result, the need exists for new therapeutic options that rapidly and reliably restore skin cosmesis and function. Here we present a new mechanobiological computational model to further the design and evaluation of next-generation regenerative dermal scaffolds fabricated from polymerizable collagen. A Bayesian framework, along with microstructure and mechanical property data from engineered dermal scaffolds and autograft skin, were used to calibrate constitutive models for collagen density, fiber alignment and dispersion, and stiffness. A chemo-bio-mechanical finite element model including collagen, cells, and representative cytokine signaling was adapted to simulate no-fill, dermal scaffold, and autograft skin outcomes observed in a preclinical animal model of full-thickness skin wounds, with a focus on permanent contraction, collagen realignment, and cellularization. Finite element model simulations demonstrated wound cellularization and contraction behavior that was similar to that observed experimentally. A sensitivity analysis suggested collagen fiber stiffness and density are important scaffold design features for predictably controlling wound contraction. Finally, prospective simulations indicated that scaffolds with increased fiber dispersion (isotropy) exhibited reduced and more uniform wound contraction while supporting cell infiltration. By capturing the link between multi-scale scaffold biomechanics and cell-scaffold mechanochemical interactions, simulated healing outcomes aligned well with preclinical animal model data. STATEMENT OF SIGNIFICANCE: Skin wounds continue to be a significant burden to patients, physicians, and the healthcare system. Advancing the mechanistic understanding of the wound healing process, including multi-scale mechanobiological interactions amongst cells, the collagen scaffolding, and signaling molecules, will aide in the design of new skin restoration therapies. This work represents the first step towards integrating mechanobiology-based computational tools with in vitro and in vivo preclinical testing data for improving the design and evaluation of custom-fabricated collagen scaffolds for dermal replacement. Such an approach has potential to expedite development of new and more effective skin restoration therapies as well as improve patient-centered wound treatment.
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31
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Bist D, Pawde AM, Amarpal, Kinjavdekar P, Mukherjee R, Singh KP, Verma MR, Sharun K, Kumar A, Dubey PK, Mohan D, Verma A, Sharma GT. Evaluation of canine bone marrow-derived mesenchymal stem cells for experimental full-thickness cutaneous wounds in a diabetic rat model. Expert Opin Biol Ther 2021; 21:1655-1664. [PMID: 34620044 DOI: 10.1080/14712598.2022.1990260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
BACKGROUND The wound healing potential of canine bone marrow-derived mesenchymal stem cells (BMSCs) was evaluated in the excisional wound of streptozotocin-induced diabetic rats. RESEARCH DESIGN AND METHODS Xenogenic BMSCs were collected aseptically from the iliac crest of healthy canine donors under general anesthesia. Full-thickness experimental wounds (20 × 20 mm2) on the dorsum of forty-eight adult healthy Wistar white rats. The wounds were assigned randomly to three treatment groups: PBS (Group A) or BMSCs (Group B) injected into the wound margins on days 0, 7, and 14 or BMSCs (Group C) injected into the wound margins on days 7, 14, and 21 post-wounding. The degree of wound healing was evaluated based on macroscopical, hemato-biochemical, histopathological, and histochemical parameters. RESULTS The results indicated granulation tissue formation with reduced exudation and peripheral swelling in the treatment groups compared to the control group A. Similarly, the degree of wound contraction was significantly higher in groups B and C animals than group A on days 14 and 21 post-wounding. The transplantation of BMSCs resulted in early drying of wounds, granulation tissue appearance, and enhanced cosmetic appearance. CONCLUSION The histopathological, histochemical, and gross findings suggested the therapeutic potential of xenogeneic mesenchymal stem cell therapy in managing diabetic wounds. ABBREVIATIONS BMSCs-bone marrow-derived mesenchymal stem cells, PBS-phosphate-buffered saline, MSCs-mesenchymal stem cells, FBS-fetal bovine serum, ECM-extracellular matrix.
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Affiliation(s)
- Deepika Bist
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India
| | - A M Pawde
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India
| | - Amarpal
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India
| | - Prakash Kinjavdekar
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India
| | - Reena Mukherjee
- Division of Medicine, ICAR-Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India
| | - K P Singh
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India
| | - Med Ram Verma
- Division of Livestock Economics, Statistics and Information Technology, ICAR-Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India
| | - Khan Sharun
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India
| | - Amit Kumar
- Animal Genetics Division, ICAR-Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India
| | - Pawan K Dubey
- Centre for Genetic Disorders, Institute of Science, Banaras Hindu University, Varanasi, India
| | - Divya Mohan
- Veterinary Surgeon, Animal Husbandry Department, Government of Kerala, India
| | - Amit Verma
- Veterinary Officer, Veterinary Hospital, Sirmour, Himachal Pradesh, India
| | - G Taru Sharma
- Division of Physiology & Climatology, ICAR-Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India
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Harada T, Yamanishi T, Kurimoto T, Uematsu S, Yamamoto Y, Inoue N, Nishio J. Long-term Morphological Changes of the Velum and the Nasopharynx in Patients With Cleft Palate. Cleft Palate Craniofac J 2021; 59:1264-1270. [PMID: 34662220 DOI: 10.1177/10556656211045287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVE To investigate long-term morphological changes in the soft palate length and nasopharynx in patients with cleft palate. We hypothesized that there would be differences in the morphological development of the soft palate and nasopharynx between patients with and without cleft palate and that these developmental changes would negatively affect the soft palate length to pharyngeal depth ratio involved in velopharyngeal closure for patients with cleft palate. DESIGN Retrospective, case-control study. SETTING Institutional practice. PATIENTS Ninety-two patients (Group F) with unilateral cleft lip, alveolus, and palate and 67 patients (Group CLA) with unilateral cleft lip and alveolus not requiring palatoplasty were included. MAIN OUTCOME MEASURES The soft palate length, nasopharyngeal size, and soft palate length to pharyngeal depth ratio were measured via lateral cephalograms obtained at three different periods. RESULTS Group F showed a shorter soft palate length and smaller nasopharyngeal size than Group CLA at all periods. Both these parameters increased with age, but the increase in amount was significantly less in Group F compared with that in Group CLA. The soft palate length to pharyngeal depth ratio in Group F decreased with age. CONCLUSIONS In patients with cleft palate, the soft palate length to pharyngeal depth ratio, which is involved in velopharyngeal closure, can change with age. Less soft palate length growth and unfavorable relationship between the soft palate and nasopharynx may be masked in early childhood but can manifest later on with age.
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Affiliation(s)
- Takeshi Harada
- 13608Osaka Women's and Children's Hospital, Izumi, Osaka, Japan.,38654Kansai Rosai Hospital, Amagasaki, Hyogo, Japan
| | | | | | - Setsuko Uematsu
- 13608Osaka Women's and Children's Hospital, Izumi, Osaka, Japan
| | - Yuri Yamamoto
- 13608Osaka Women's and Children's Hospital, Izumi, Osaka, Japan
| | - Naoko Inoue
- 13608Osaka Women's and Children's Hospital, Izumi, Osaka, Japan
| | - Juntaro Nishio
- 13608Osaka Women's and Children's Hospital, Izumi, Osaka, Japan
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33
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Xu FW, Lv YL, Zhong YF, Xue YN, Wang Y, Zhang LY, Hu X, Tan WQ. Beneficial Effects of Green Tea EGCG on Skin Wound Healing: A Comprehensive Review. Molecules 2021; 26:6123. [PMID: 34684703 PMCID: PMC8540743 DOI: 10.3390/molecules26206123] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 10/02/2021] [Accepted: 10/04/2021] [Indexed: 12/18/2022] Open
Abstract
Epigallocatechin gallate (EGCG) is associated with various health benefits. In this review, we searched current work about the effects of EGCG and its wound dressings on skin for wound healing. Hydrogels, nanoparticles, micro/nanofiber networks and microneedles are the major types of EGCG-containing wound dressings. The beneficial effects of EGCG and its wound dressings at different stages of skin wound healing (hemostasis, inflammation, proliferation and tissue remodeling) were summarized based on the underlying mechanisms of antioxidant, anti-inflammatory, antimicrobial, angiogenesis and antifibrotic properties. This review expatiates on the rationale of using EGCG to promote skin wound healing and prevent scar formation, which provides a future clinical application direction of EGCG.
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Affiliation(s)
- Fa-Wei Xu
- Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou 310016, China; (F.-W.X.); (Y.-F.Z.); (Y.-N.X.); (Y.W.); (L.-Y.Z.); (X.H.)
| | - Ying-Li Lv
- Tea Research Institute, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310013, China;
| | - Yu-Fan Zhong
- Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou 310016, China; (F.-W.X.); (Y.-F.Z.); (Y.-N.X.); (Y.W.); (L.-Y.Z.); (X.H.)
| | - Ya-Nan Xue
- Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou 310016, China; (F.-W.X.); (Y.-F.Z.); (Y.-N.X.); (Y.W.); (L.-Y.Z.); (X.H.)
| | - Yong Wang
- Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou 310016, China; (F.-W.X.); (Y.-F.Z.); (Y.-N.X.); (Y.W.); (L.-Y.Z.); (X.H.)
| | - Li-Yun Zhang
- Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou 310016, China; (F.-W.X.); (Y.-F.Z.); (Y.-N.X.); (Y.W.); (L.-Y.Z.); (X.H.)
| | - Xian Hu
- Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou 310016, China; (F.-W.X.); (Y.-F.Z.); (Y.-N.X.); (Y.W.); (L.-Y.Z.); (X.H.)
| | - Wei-Qiang Tan
- Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou 310016, China; (F.-W.X.); (Y.-F.Z.); (Y.-N.X.); (Y.W.); (L.-Y.Z.); (X.H.)
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Yannas IV, Tzeranis DS. Mammals fail to regenerate organs when wound contraction drives scar formation. NPJ Regen Med 2021; 6:39. [PMID: 34294726 PMCID: PMC8298605 DOI: 10.1038/s41536-021-00149-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 07/07/2021] [Indexed: 12/19/2022] Open
Abstract
To understand why mammals generally do not regenerate injured organs, we considered the exceptional case of spontaneous skin regeneration in the early lamb fetus. Whereas during the early fetal stage skin wounds heal by regeneration, in the late fetal stage, and after birth, skin wounds close instead by scar formation. We review independent evidence that this switch in wound healing response coincides with the onset of wound contraction, which is also enabled during late fetal gestation. The crucial role of wound contraction in determining the wound healing outcome in adults has been demonstrated in three mammalian models of severe injury (excised guinea pig skin, transected rat sciatic nerve, excised rabbit conjunctival stroma) where grafting the injury with DRT, a contraction-blocking scaffold of highly-specific structure, altered significantly the wound healing outcome. While spontaneous healing resulted in scar formation in these animal models, DRT grafting significantly reduced the extent of wound contraction, prevented scar synthesis, and resulted in partial regeneration. These findings, as well as independent data from species that heal spontaneously via regeneration, point to a striking hypothesis: The process of regeneration lies dormant in mammals until appropriately activated by injury. In spontaneous wound healing of the late fetus and in adult mammals, wound contraction impedes such endogenous regeneration mechanisms. However, engineered treatments, such as DRT, that block wound contraction can cancel its effects and favor wound healing by regeneration instead of scar formation.
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Affiliation(s)
- Ioannis V Yannas
- Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
| | - Dimitrios S Tzeranis
- Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia, Cyprus
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Zhu HJ, Fan M, Gao W. Identification of potential hub genes associated with skin wound healing based on time course bioinformatic analyses. BMC Surg 2021; 21:303. [PMID: 34193119 PMCID: PMC8243612 DOI: 10.1186/s12893-021-01298-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 06/04/2021] [Indexed: 12/02/2022] Open
Abstract
Background The skin is the largest organ of the body and has multiple functions. Wounds remain a significant healthcare problem due to the large number of traumatic and pathophysiological conditions patients suffer. Methods Gene expression profiles of 37 biopsies collected from patients undergoing split-thickness skin grafts at five different time points were downloaded from two datasets (GSE28914 and GSE50425) in the Gene Expression Omnibus (GEO) database. Principal component analysis (PCA) was applied to classify samples into different phases. Subsequently, differentially expressed genes (DEGs) analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functional enrichment analyses were performed, and protein–protein interaction (PPI) networks created for each phase. Furthermore, based on the results of the PPI, hub genes in each phase were identified by molecular complex detection combined with the ClueGO algorithm. Results Using principal component analysis, the collected samples were divided into four phases, namely intact phase, acute wound phase, inflammatory and proliferation phase, and remodeling phase. Intact samples were used as control group. In the acute wound phase, a total of 1 upregulated and 100 downregulated DEGs were identified. Tyrosinase (TYR), tyrosinase Related Protein 1 (TYRP1) and dopachrome tautomerase (DCT) were considered as hub genes and enriched in tyrosine metabolism which dominate the process of melanogenesis. In the inflammatory and proliferation phase, a total of 85 upregulated and 164 downregulated DEGs were identified. CHEK1, CCNB1 and CDK1 were considered as hub genes and enriched in cell cycle and P53 signaling pathway. In the remodeling phase, a total of 121 upregulated and 49 downregulated DEGs were identified. COL4A1, COL4A2, and COL6A1 were considered as hub genes and enriched in protein digestion and absorption, and ECM-receptor interaction. Conclusion This comprehensive bioinformatic re-analysis of GEO data provides new insights into the molecular pathogenesis of wound healing and the potential identification of therapeutic targets for the treatment of wounds. Supplementary Information The online version contains supplementary material available at 10.1186/s12893-021-01298-w.
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Affiliation(s)
- Hai-Jun Zhu
- The 4th People's Hospital of Shenyang, No. 20 Huanghenan Street, Huanggu District, Shenyang, 110031, China
| | - Meng Fan
- The 4th People's Hospital of Shenyang, No. 20 Huanghenan Street, Huanggu District, Shenyang, 110031, China
| | - Wei Gao
- The 4th People's Hospital of Shenyang, No. 20 Huanghenan Street, Huanggu District, Shenyang, 110031, China.
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Campitiello F, Mancone M, Cammarota M, D’Agostino A, Ricci G, Stellavato A, Della Corte A, Pirozzi AVA, Scialla G, Schiraldi C, Canonico S. Acellular Dermal Matrix Used in Diabetic Foot Ulcers: Clinical Outcomes Supported by Biochemical and Histological Analyses. Int J Mol Sci 2021; 22:7085. [PMID: 34209306 PMCID: PMC8267704 DOI: 10.3390/ijms22137085] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 06/10/2021] [Accepted: 06/23/2021] [Indexed: 01/21/2023] Open
Abstract
Diabetic foot ulcer (DFU) is a diabetes complication which greatly impacts the patient's quality of life, often leading to amputation of the affected limb unless there is a timely and adequate management of the patient. DFUs have a high economic impact for the national health system. Data have indeed shown that DFUs are a major cause of hospitalization for patients with diabetes. Based on that, DFUs represent a very important challenge for the national health system. Especially in developed countries diabetic patients are increasing at a very high rate and as expected, also the incidence of DFUs is increasing due to longevity of diabetic patients in the western population. Herein, the surgical approach focused on the targeted use of the acellular dermal matrix has been integrated with biochemical and morphological/histological analyses to obtain evidence-based information on the mechanisms underlying tissue regeneration. In this research report, the clinical results indicated decreased postoperative wound infection levels and a short healing time, with a sound regeneration of tissues. Here we demonstrate that the key biomarkers of wound healing process are activated at gene expression level and also synthesis of collagen I, collagen III and elastin is prompted and modulated within the 28-day period of observation. These analyses were run on five patients treated with Integra® sheet and five treated with the injectable matrix Integra® Flowable, for cavitary lesions. In fact, clinical evaluation of improved healing was, for the first time, supported by biochemical and histological analyses. For these reasons, the present work opens a new scenario in DFUs treatment and follow-up, laying the foundation for a tailored protocol towards complete healing in severe pathological conditions.
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Affiliation(s)
- Ferdinando Campitiello
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Miraglia 2, 80138 Naples, Italy; (F.C.); (A.D.C.); (G.S.); (S.C.)
| | - Manfredi Mancone
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Miraglia 2, 80138 Naples, Italy; (F.C.); (A.D.C.); (G.S.); (S.C.)
| | - Marcella Cammarota
- Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy; (M.C.); (A.D.); (G.R.); (A.S.); (A.V.A.P.); (C.S.)
| | - Antonella D’Agostino
- Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy; (M.C.); (A.D.); (G.R.); (A.S.); (A.V.A.P.); (C.S.)
| | - Giulia Ricci
- Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy; (M.C.); (A.D.); (G.R.); (A.S.); (A.V.A.P.); (C.S.)
| | - Antonietta Stellavato
- Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy; (M.C.); (A.D.); (G.R.); (A.S.); (A.V.A.P.); (C.S.)
| | - Angela Della Corte
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Miraglia 2, 80138 Naples, Italy; (F.C.); (A.D.C.); (G.S.); (S.C.)
| | - Anna Virginia Adriana Pirozzi
- Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy; (M.C.); (A.D.); (G.R.); (A.S.); (A.V.A.P.); (C.S.)
| | - Gianluca Scialla
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Miraglia 2, 80138 Naples, Italy; (F.C.); (A.D.C.); (G.S.); (S.C.)
| | - Chiara Schiraldi
- Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy; (M.C.); (A.D.); (G.R.); (A.S.); (A.V.A.P.); (C.S.)
| | - Silvestro Canonico
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Miraglia 2, 80138 Naples, Italy; (F.C.); (A.D.C.); (G.S.); (S.C.)
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Echternacht SR, Chacon MA, Leckenby JI. Central versus peripheral nervous system regeneration: is there an exception for cranial nerves? Regen Med 2021; 16:567-579. [PMID: 34075805 DOI: 10.2217/rme-2020-0096] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
There exists a dichotomy in regenerative capacity between the PNS and CNS, which poses the question - where do cranial nerves fall? Through the discussion of the various cells and processes involved in axonal regeneration, we will evaluate whether the assumption that cranial nerve regeneration is analogous to peripheral nerve regeneration is valid. It is evident from this review that much remains to be clarified regarding both PNS and CNS regeneration. Furthermore, it is not clear if cranial nerves follow the PNS model, CNS model or possess an alternative novel regenerative process altogether. Future research should continue to focus on elucidating how cranial nerves regenerate; and the various cellular interactions, molecules and pathways involved.
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Affiliation(s)
- Scott R Echternacht
- University of Rochester School of Medicine & Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA.,Division of Plastic Surgery, University of Rochester Medical Center, 601 Elmwood Avenue, Box 661, Rochester, NY 14642, USA
| | - Miranda A Chacon
- Division of Plastic Surgery, University of Rochester Medical Center, 601 Elmwood Avenue, Box 661, Rochester, NY 14642, USA.,Department of Surgery, University of Rochester Medical Center, 601 Elmwood Avenue, Box 661, Rochester, NY 14642, USA
| | - Jonathan I Leckenby
- Division of Plastic Surgery, University of Rochester Medical Center, 601 Elmwood Avenue, Box 661, Rochester, NY 14642, USA
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Xydias D, Ziakas G, Psilodimitrakopoulos S, Lemonis A, Bagli E, Fotsis T, Gravanis A, Tzeranis DS, Stratakis E. Three-dimensional characterization of collagen remodeling in cell-seeded collagen scaffolds via polarization second harmonic generation. BIOMEDICAL OPTICS EXPRESS 2021; 12:1136-1153. [PMID: 33680563 PMCID: PMC7901316 DOI: 10.1364/boe.411501] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 11/24/2020] [Accepted: 12/01/2020] [Indexed: 05/08/2023]
Abstract
In this study, we use non-linear imaging microscopy to characterize the structural properties of porous collagen-GAG scaffolds (CGS) seeded with human umbilical vein endothelial cells (HUVECs), as well as human mesenchymal stem cells (hMSCs), a co-culture previously reported to form vessel-like structures inside CGS. The evolution of the resulting tissue construct was monitored over 10 days via simultaneous two- and three-photon excited fluorescence microscopy. Time-lapsed 2- and 3-photon excited fluorescence imaging was utilized to monitor the temporal evolution of the vascular-like structures up to 100 µm inside the scaffold up to 10 days post-seeding. 3D polarization-dependent second harmonic generation (PSHG) was utilized to monitor collagen-based scaffold remodeling and determine collagen fibril orientation up to 200 µm inside the scaffold. We demonstrate that polarization-dependent second harmonic generation can provide a novel way to quantify the reorganization of the collagen architecture in CGS simultaneously with key biomechanical interactions between seeded cells and CGS that regulate the formation of vessel-like structures inside 3D tissue constructs. A comparison between samples at different days in vitro revealed that gradually, the scaffolds developed an orthogonal net-like architecture, previously found in real skin.
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Affiliation(s)
- Dionysios Xydias
- Institute of Electronic Structure and Laser, Foundation for Research and Technology-Hellas, Greece
- Department of Materials Science and Technology, School of Sciences and Engineering, University of Crete, Greece
| | - Georgios Ziakas
- Department of Materials Science and Technology, School of Sciences and Engineering, University of Crete, Greece
| | | | - Andreas Lemonis
- Institute of Electronic Structure and Laser, Foundation for Research and Technology-Hellas, Greece
| | - Eleni Bagli
- Department of Biomedical Research, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Ioannina, Greece
| | - Theodore Fotsis
- Department of Biomedical Research, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Ioannina, Greece
| | - Achille Gravanis
- Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Greece
- Department of Pharmacology, School of Medicine, University of Crete, Greece
| | - Dimitrios S. Tzeranis
- Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Greece
- Department of Mechanical and Manufacturing Engineering, University of Cyprus, Cyprus, Greece
| | - Emmanuel Stratakis
- Institute of Electronic Structure and Laser, Foundation for Research and Technology-Hellas, Greece
- Department of Physics, School of Sciences and Engineering, University of Crete, Greece
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Abstract
BACKGROUND Proliferative vitreoretinopathy (PVR) is still an unsolved problem after half a century of research. METHODS This article provides a review of mechanisms leading to PVR in the context of wound healing research. RESULTS Wound healing is a physiological repair process that occurs in a similar way in all organs and may end in scar formation. The development of PVR is based on this wound healing mechanism. The localization and structures involved lead to specific characteristics and consequences. Up to now the pharmacotherapeutic strategies were not sufficiently effective. The growing understanding of the mechanisms of scar-free fetal wound healing, could however lead to a solution of the PVR problem. CONCLUSION The PVR is a physiological process with a pathological result. The complex steps involved in vitreoretinal wound healing are well understood. There is currently no therapeutic approach neither in ophthalmology nor in other medical disciplines that is able to restore the original function and structure of the involved tissue or organ but there is hope that this can succeed in the future.
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Rahman MT, Hasan M, Hossain MT, Islam MS, Rahman MA, Alam MR, Juyena NS. Differential efficacies of marigold leaves and turmeric paste on the healing of the incised wound in sheep. J Adv Vet Anim Res 2020; 7:750-757. [PMID: 33409322 PMCID: PMC7774798 DOI: 10.5455/javar.2020.g477] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 11/15/2020] [Accepted: 11/15/2020] [Indexed: 11/25/2022] Open
Abstract
Objective: This study was undertaken to compare the curative efficacy of marigold leaf paste and turmeric paste on healing the incised wound in sheep. The study also determined the antimicrobial effects and histopathological changes in a wound’s healing process treated with these medicinal herbs. Materials and Methods: Surgical wounds (n = 18) were created aseptically in the skin of the flank region of six healthy sheep dividing them into three experimental groups. Follow-up data were taken up to day 21. Different morphological characteristics of the wound and wound contraction (length and width) were recorded weekly. Samples were collected on days 1, 2, and 3 to test the antimicrobial effects and on days 1, 3, and 7 for histopathological studies. Results: Treatment with marigold leaf paste and turmeric paste resulted in a swelled wound area of 11.78 ± 0.38 mm and 11.52 ± 0.27 mm, respectively. The wound areas were comparatively lower than that of the control group (11.44 ± 0.20 mm). Moreover, the least elevation (2.44 ± 0.12 mm) of the sutured line from the skin surface was noted and compared between the marigold leaf paste and normal saline (2.74 ± 0.13 mm). Bacterial colonies in the nutrient agar medium cultured with swabs from the normal saline-treated group’s wound area were found on day 1. On the contrary, bacterial colonies were absent on days 2 and 3 of treatment in the groups treated with both the paste of marigold leaves and turmeric. Less intense tissue reactions and higher keratinization of epithelium were shown in the group treated with marigold leaf paste than turmeric paste and saline-treated groups. Conclusion: Marigold leaf paste showed less tissue reaction and healed the wounds effectively. Thus, this paste could be used for the treatment of superficial wounds in sheep.
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Affiliation(s)
- Md Tuhinur Rahman
- Department of Surgery and Obstetrics, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh.,Department of Surgery and Radiology, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur, Bangladesh
| | - Moinul Hasan
- Department of Surgery and Obstetrics, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh
| | - Muhammad Tofazzal Hossain
- Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh
| | - Md Sayedul Islam
- Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh.,Department of Microbiology and Public Health, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur, Bangladesh
| | - Md Ataur Rahman
- Department of Surgery and Radiology, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur, Bangladesh
| | - Md Rafiqul Alam
- Department of Surgery and Obstetrics, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh
| | - Nasrin Sultana Juyena
- Department of Surgery and Obstetrics, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh
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Shafiee A, Cavalcanti AS, Saidy NT, Schneidereit D, Friedrich O, Ravichandran A, De-Juan-Pardo EM, Hutmacher DW. Convergence of 3D printed biomimetic wound dressings and adult stem cell therapy. Biomaterials 2020; 268:120558. [PMID: 33307369 DOI: 10.1016/j.biomaterials.2020.120558] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 11/16/2020] [Accepted: 11/18/2020] [Indexed: 02/06/2023]
Abstract
Biomimetically designed medical-grade polycaprolactone (mPCL) dressings are 3D-printed with pore architecture and anisotropic mechanical characteristics that favor skin wound healing with reduced scarring. Melt electrowritten mPCL dressings are seeded with human gingival tissue multipotent mesenchymal stem/stromal cells and cryopreserved using a clinically approved method. The regenerative potential of fresh or frozen cell-seeded mPCL dressing is compared in a splinted full-thickness excisional wound in a rat model over six weeks. The application of 3D-printed mPCL dressings decreased wound contracture and significantly improved skin regeneration through granulation and re-epithelialization compared to control groups. Combining 3D-printed biomimetic wound dressings and precursor cell delivery enhances physiological wound closure with reduced scar tissue formation.
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Affiliation(s)
- Abbas Shafiee
- Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove, Brisbane, QLD, 4059, Australia; UQ Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, QLD, 4102, Australia; Herston Biofabrication Institute, Metro North Hospital and Health Service, Brisbane, QLD, 4029, Australia.
| | - Amanda S Cavalcanti
- Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove, Brisbane, QLD, 4059, Australia
| | - Navid T Saidy
- Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove, Brisbane, QLD, 4059, Australia; The University of Queensland, School of Dentistry, Herston, Queensland, Australia
| | - Dominik Schneidereit
- Institute of Medical Biotechnology, Friedrich-Alexander-University Erlangen-Nuremberg, Paul-Gordan-Str.3, 91052, Erlangen, Germany
| | - Oliver Friedrich
- Institute of Medical Biotechnology, Friedrich-Alexander-University Erlangen-Nuremberg, Paul-Gordan-Str.3, 91052, Erlangen, Germany
| | - Akhilandeshwari Ravichandran
- Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove, Brisbane, QLD, 4059, Australia
| | - Elena M De-Juan-Pardo
- Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove, Brisbane, QLD, 4059, Australia
| | - Dietmar W Hutmacher
- Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove, Brisbane, QLD, 4059, Australia; Australian Research Council (ARC) Training Centre in Additive Biomanufacturing, Queensland University of Technology (QUT), Kelvin Grove, QLD, 4059, Australia.
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Sia DK, Mensah KB, Opoku-Agyemang T, Folitse RD, Darko DO. Mechanisms of ivermectin-induced wound healing. BMC Vet Res 2020; 16:397. [PMID: 33081763 PMCID: PMC7576857 DOI: 10.1186/s12917-020-02612-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 10/06/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Wounds cause structural and functional discontinuity of an organ. Wound healing, therefore, seeks to re-establish the normal morphology and functionality through intertwined stages of hemostasis, inflammation, proliferation, and tissue remodelling. Ivermectin, a macrolide, has been used as an endectoparasiticide in human and veterinary medicine practice for decades. Here, we show that ivermectin exhibits wounding healing activity by mechanisms independent of its well-known antiparasitic activity. This study aimed to evaluate the wound healing property of ivermectin cream using histochemistry and enzyme-linked immunosorbent assay techniques. RESULTS Non-irritant dose of ivermectin cream (0.03-1%) decreased wound macroscopic indices such as exudation, edge edema, hyperemia, and granulation tissue deposition by day 9 compared to day 13 for the vehicle-treated group. This corresponded with a statistically significant wound contraction rate, hydroxyproline deposition, and a decreased time to heal rate. The levels of growth factors TGF-β1 and VEGF were significantly elevated on day 7 but decreased on day 21. This corresponded with changes in cytokines (IL-1α, IL-4, IL-10, and TNF-α) and eicosanoids (LTB4, PGE2, and PGD2) levels on days 7 and 21.. Interestingly, low doses of ivermectin cream (0.03-0.1%) induced wound healing with minimal scarring compared to higher doses of the cream and the positive control, Silver Sulfadiazine. CONCLUSION Ivermectin promotes wound healing partly through modulation of the inflammatory process and the levels of Transforming Growth Factor-Beta 1 and Vascular Endothelial Growth Factor. Low doses of ivermectin cream have the potential to be used in treating wounds with minimal scar tissue formation.
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Affiliation(s)
- Daniel Kwesi Sia
- Department of Pharmacology, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
- School of Veterinary Medicine, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Kwesi Boadu Mensah
- Department of Pharmacology, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
| | - Tony Opoku-Agyemang
- School of Veterinary Medicine, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Raphael D Folitse
- School of Veterinary Medicine, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - David Obiri Darko
- Department of Pharmacology, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
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Santarella F, Sridharan R, Marinkovic M, Do Amaral RJFC, Cavanagh B, Smith A, Kashpur O, Gerami‐Naini B, Garlick JA, O'Brien FJ, Kearney CJ. Scaffolds Functionalized with Matrix from Induced Pluripotent Stem Cell Fibroblasts for Diabetic Wound Healing. Adv Healthc Mater 2020; 9:e2000307. [PMID: 32597577 DOI: 10.1002/adhm.202000307] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 06/12/2020] [Indexed: 12/15/2022]
Abstract
Diabetic foot ulcers (DFUs) are chronic wounds, with 20% of cases resulting in amputation, despite intervention. A recently approved tissue engineering product-a cell-free collagen-glycosaminoglycan (GAG) scaffold-demonstrates 50% success, motivating its functionalization with extracellular matrix (ECM). Induced pluripotent stem cell (iPSC) technology reprograms somatic cells into an embryonic-like state. Recent findings describe how iPSCs-derived fibroblasts ("post-iPSF") are proangiogenic, produce more ECM than their somatic precursors ("pre-iPSF"), and their ECM has characteristics of foetal ECM (a wound regeneration advantage, as fetuses heal scar-free). ECM production is 45% higher from post-iPSF and has favorable components (e.g., Collagen I and III, and fibronectin). Herein, a freeze-dried scaffold using ECM grown by post-iPSF cells (Post-iPSF Coll) is developed and tested vs precursors ECM-activated scaffolds (Pre-iPSF Coll). When seeded with healthy or DFU fibroblasts, both ECM-derived scaffolds have more diverse ECM and more robust immune responses to cues. Post-iPSF-Coll had higher GAG, higher cell content, higher Vascular Endothelial Growth Factor (VEGF) in DFUs, and higher Interleukin-1-receptor antagonist (IL-1ra) vs. pre-iPSF Coll. This work constitutes the first step in exploiting ECM from iPSF for tissue engineering scaffolds.
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Affiliation(s)
- Francesco Santarella
- Royal College of Surgeons in Ireland 123 St Stephen's Green, Saint Peter's Dublin D02 YN77 Ireland
| | - Rukmani Sridharan
- Royal College of Surgeons in Ireland 123 St Stephen's Green, Saint Peter's Dublin D02 YN77 Ireland
| | - Milica Marinkovic
- Royal College of Surgeons in Ireland 123 St Stephen's Green, Saint Peter's Dublin D02 YN77 Ireland
| | - Ronaldo Jose Farias Correa Do Amaral
- Royal College of Surgeons in Ireland 123 St Stephen's Green, Saint Peter's Dublin D02 YN77 Ireland
- Biomedical Sciences, National University of Ireland Galway Newcastle Road Galway H91 W2TY Ireland
| | - Brenton Cavanagh
- Royal College of Surgeons in Ireland 123 St Stephen's Green, Saint Peter's Dublin D02 YN77 Ireland
| | - Avi Smith
- Department of Diagnostic SciencesTufts University School of Dental Medicine Boston MA 02111 USA
| | - Olga Kashpur
- Department of Diagnostic SciencesTufts University School of Dental Medicine Boston MA 02111 USA
| | - Behzad Gerami‐Naini
- Department of Diagnostic SciencesTufts University School of Dental Medicine Boston MA 02111 USA
| | - Jonathan A. Garlick
- Department of Diagnostic SciencesTufts University School of Dental Medicine Boston MA 02111 USA
| | - Fergal J. O'Brien
- Royal College of Surgeons in Ireland 123 St Stephen's Green, Saint Peter's Dublin D02 YN77 Ireland
- The University of Dublin Trinity College, College Street Dublin Dublin 2, D02 R590 Ireland
- Advanced Materials and Bioengineering Research Centre (AMBER)RCSI and TCD Dublin D02 HP52 Ireland
| | - Cathal J. Kearney
- Royal College of Surgeons in Ireland 123 St Stephen's Green, Saint Peter's Dublin D02 YN77 Ireland
- The University of Dublin Trinity College, College Street Dublin Dublin 2, D02 R590 Ireland
- Advanced Materials and Bioengineering Research Centre (AMBER)RCSI and TCD Dublin D02 HP52 Ireland
- Department of Biomedical EngineeringUniversity of Massachusetts Amherst Amherst MA 01003‐9292 USA
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Giri VP, Pandey S, Kumari M, Paswan SK, Tripathi A, Srivastava M, Rao CV, Katiyar R, Nautiyal CS, Mishra A. Biogenic silver nanoparticles as a more efficient contrivance for wound healing acceleration than common antiseptic medicine. FEMS Microbiol Lett 2020; 366:5580583. [PMID: 31580434 DOI: 10.1093/femsle/fnz201] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Accepted: 10/02/2019] [Indexed: 12/13/2022] Open
Abstract
A simple and facile way of using biogenic silver nanoparticles (BSNP) (10-20 nm) was developed for wound healing acceleration and suppression of wound infections. The BSNP were formulated in an ointment base, and the study to accelerate the wound healing process was conducted in a rat. The pH of the BSNP ointment, pH 6.8 ± 0.5, lies in normal pH range of the human skin, with good spreadability and diffusibility. The wound closure rate, as a percentage, was highest at day 3 for a BSNP ointment-treated wound at 22.77 ± 1.60%, while in an untreated control the rate was 10.99 ± 1.74%, for Betadine 14.73 ± 2.36% and for Soframycin 18.55 ± 1.37%, compared with day 0. A similar pattern of wound closure rate was found at days 7 and 11. The antibacterial activity of BSNP was evaluated against wound-infection-causing bacteria Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli by the agar diffusion method. The total bacterial counts in the wound area were enumerated by the colony forming unit method. The lowest number of bacterial counts was found in the BSNP-treated wound compared with the other groups. BSNP treatment at 7.5% concentration enhanced migration of fibroblasts in a scratch assay. These findings reveal BSNP as an efficient contrivance for wound healing acceleration and as an eco-friendly alternative therapeutic antimicrobial agent.
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Affiliation(s)
- Ved Prakash Giri
- CSIR-Division of Microbial Technology, National Botanical Research Institute, Rana Pratap Marg, Lucknow, 226001, India.,Department of Botany, Lucknow University, Hasanganj, Lucknow 226007, India
| | - Shipra Pandey
- CSIR-Division of Microbial Technology, National Botanical Research Institute, Rana Pratap Marg, Lucknow, 226001, India.,Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Madhuree Kumari
- CSIR-Division of Microbial Technology, National Botanical Research Institute, Rana Pratap Marg, Lucknow, 226001, India.,Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Shravan Kumar Paswan
- CSIR-Division of Microbial Technology, National Botanical Research Institute, Rana Pratap Marg, Lucknow, 226001, India
| | - Ashutosh Tripathi
- CSIR-Division of Microbial Technology, National Botanical Research Institute, Rana Pratap Marg, Lucknow, 226001, India
| | - Manjoosha Srivastava
- CSIR-Division of Microbial Technology, National Botanical Research Institute, Rana Pratap Marg, Lucknow, 226001, India
| | - Chandana Venketswara Rao
- CSIR-Division of Microbial Technology, National Botanical Research Institute, Rana Pratap Marg, Lucknow, 226001, India
| | - Ratna Katiyar
- Department of Botany, Lucknow University, Hasanganj, Lucknow 226007, India
| | - Chandra Shekhar Nautiyal
- CSIR-Division of Microbial Technology, National Botanical Research Institute, Rana Pratap Marg, Lucknow, 226001, India
| | - Aradhana Mishra
- CSIR-Division of Microbial Technology, National Botanical Research Institute, Rana Pratap Marg, Lucknow, 226001, India.,Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
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45
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Han B, Fang WH, Zhao S, Yang Z, Hoang BX. Zinc sulfide nanoparticles improve skin regeneration. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2020; 29:102263. [PMID: 32645446 DOI: 10.1016/j.nano.2020.102263] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 06/24/2020] [Accepted: 06/27/2020] [Indexed: 02/08/2023]
Abstract
Wound healing has been intensely studied to expedite recovery times and reduce scarring. However, current technologies fail to achieve regenerative capabilities, leaving wounds with scarring and lack of skin accessories. The recent emergence of nanotechnology has provided a new clinical modality of zinc nanoparticles in wound care. This present study investigated Zinc Sulfide nanoparticles (ZnS-NP) on wound healing in vitro with 2D and 3D models and in vivo with rat full-thickness wound model. ZnS-NP inhibited fetal bovine serum-stimulated rat skin fibroblast cell proliferation, altered cytoskeletal organization, and reduced collagen synthesis as well as contractile activity. ZnS-NP regulated redox homeostatsis and promoted fibroblast viability in 3D hypoxia conditions. In the rat full-thickness wound model, ZnS-NP reduced wound contraction, enhanced re-epithelization, and promoted skin appendage formation. The biological activities of ZnS-NPs determined in our current study may suggest promising practical applications for topical or systemic treatment for wound repair.
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Affiliation(s)
- Bo Han
- Department of Surgery, Keck School of Medicine of USC, Los Angeles, California; Department of Surgery and Biomedical Engineering, Keck School of Medicine USC, Los Angeles, CA.
| | - William H Fang
- Department of Surgery, Keck School of Medicine of USC, Los Angeles, California
| | - Shuqing Zhao
- Department of Surgery, Keck School of Medicine of USC, Los Angeles, California
| | - Zhi Yang
- Department of Surgery, Keck School of Medicine of USC, Los Angeles, California
| | - Ba X Hoang
- Department of Surgery, Keck School of Medicine of USC, Los Angeles, California
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46
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Chan WW, Yeo DCL, Tan V, Singh S, Choudhury D, Naing MW. Additive Biomanufacturing with Collagen Inks. Bioengineering (Basel) 2020; 7:bioengineering7030066. [PMID: 32630194 PMCID: PMC7552643 DOI: 10.3390/bioengineering7030066] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 06/22/2020] [Accepted: 06/25/2020] [Indexed: 12/13/2022] Open
Abstract
Collagen is a natural polymer found abundantly in the extracellular matrix (ECM). It is easily extracted from a variety of sources and exhibits excellent biological properties such as biocompatibility and weak antigenicity. Additionally, different processes allow control of physical and chemical properties such as mechanical stiffness, viscosity and biodegradability. Moreover, various additive biomanufacturing technology has enabled layer-by-layer construction of complex structures to support biological function. Additive biomanufacturing has expanded the use of collagen biomaterial in various regenerative medicine and disease modelling application (e.g., skin, bone and cornea). Currently, regulatory hurdles in translating collagen biomaterials still remain. Additive biomanufacturing may help to overcome such hurdles commercializing collagen biomaterials and fulfill its potential for biomedicine.
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Affiliation(s)
- Weng Wan Chan
- Biomanufacturing Technology, Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), Singapore City 138668, Singapore; (W.W.C.); (D.C.L.Y.); (V.T.); (S.S.)
| | - David Chen Loong Yeo
- Biomanufacturing Technology, Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), Singapore City 138668, Singapore; (W.W.C.); (D.C.L.Y.); (V.T.); (S.S.)
| | - Vernice Tan
- Biomanufacturing Technology, Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), Singapore City 138668, Singapore; (W.W.C.); (D.C.L.Y.); (V.T.); (S.S.)
| | - Satnam Singh
- Biomanufacturing Technology, Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), Singapore City 138668, Singapore; (W.W.C.); (D.C.L.Y.); (V.T.); (S.S.)
| | - Deepak Choudhury
- Biomanufacturing Technology, Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), Singapore City 138668, Singapore; (W.W.C.); (D.C.L.Y.); (V.T.); (S.S.)
- Correspondence: (D.C.); (M.W.N.)
| | - May Win Naing
- Biomanufacturing Technology, Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), Singapore City 138668, Singapore; (W.W.C.); (D.C.L.Y.); (V.T.); (S.S.)
- Singapore Institute of Manufacturing Technology (SIMTech), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, #08-04, Innovis, Singapore City 138634, Singapore
- Correspondence: (D.C.); (M.W.N.)
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47
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Giovannini UM, Teot L. Long-term follow-up comparison of two different bi-layer dermal substitutes in tissue regeneration: Clinical outcomes and histological findings. Int Wound J 2020; 17:1545-1547. [PMID: 32359006 DOI: 10.1111/iwj.13381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 04/13/2020] [Indexed: 12/01/2022] Open
Affiliation(s)
| | - Luc Teot
- Department of Plastic Reconstructive Surgery, Rigenera Clinic, Milan, Italy
- Department of Plastic Reconstructive Surgery, CHU Montpellier, Montpellier, France
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48
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Sohutskay DO, Buno KP, Tholpady SS, Nier SJ, Voytik-Harbin SL. Design and biofabrication of dermal regeneration scaffolds: role of oligomeric collagen fibril density and architecture. Regen Med 2020; 15:1295-1312. [PMID: 32228274 DOI: 10.2217/rme-2019-0084] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Aim: To evaluate dermal regeneration scaffolds custom-fabricated from fibril-forming oligomeric collagen where the total content and spatial gradient of collagen fibrils was specified. Materials & methods: Microstructural and mechanical features were verified by electron microscopy and tensile testing. The ability of dermal scaffolds to induce regeneration of rat full-thickness skin wounds was determined and compared with no fill control, autograft skin and a commercial collagen dressing. Results: Increasing fibril content of oligomer scaffolds inhibited wound contraction and decreased myofibroblast marker expression. Cellular and vascular infiltration of scaffolds over the 14-day period varied with the graded density and orientation of fibrils. Conclusion: Fibril content, spatial gradient and orientation are important collagen scaffold design considerations for promoting vascularization and dermal regeneration while reducing wound contraction.
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Affiliation(s)
- David O Sohutskay
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.,Medical Scientist Training Program, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Kevin P Buno
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA
| | - Sunil S Tholpady
- Division of Plastic Surgery, Department of Surgery, Indiana University, IN 46202, USA.,Division of Plastic Surgery, Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, IN 46202, USA
| | - Samantha J Nier
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA
| | - Sherry L Voytik-Harbin
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.,Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907, USA
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49
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Abstract
Wound healing is a complex physiological process that occurs in the human body involving the sequential activation of multiple cell types and signaling pathways in a coordinated manner. Chronic wounds and burns clearly decrease quality of life of the patients since they are associated with an increase in physical pain and socio-economical complications. Furthermore, incidence and prevalence of chronic wounds (unlike burns) have been increasing mainly due to population aging resulting in increased costs for national health systems. Thus, the development of new and more cost-effective technologies/therapies is not only of huge interest but also necessary to improve the long-term sustainability of national health systems. This review covers the current knowledge on recent technologies/therapies for skin regeneration, such as: wound dressings; skin substitutes; exogenous growth factor based therapy and systemic therapy; external tissue expanders; negative pressure; oxygen; shock wave, and photobiomodulation wound therapies. Associated benefits and risks as well as the clinical use and availability are all addressed for each therapy. Moreover, future trends in wound care including novel formulations using metallic nanoparticles and topical insulin are herein presented. These novel formulations have shown to be promising therapeutic options in the near future that may change the wound care paradigm.
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Affiliation(s)
- André Oliveira
- Faculty of Pharmacy, Universidade de Lisboa, Lisboa, Portugal
| | - Sandra Simões
- Faculty of Pharmacy, Research Institute for Medicines, iMed.ULisboa, Universidade de Lisboa, Lisboa, Portugal
| | - Andreia Ascenso
- Faculty of Pharmacy, Research Institute for Medicines, iMed.ULisboa, Universidade de Lisboa, Lisboa, Portugal
| | - Catarina Pinto Reis
- Faculty of Pharmacy, Research Institute for Medicines, iMed.ULisboa, Universidade de Lisboa, Lisboa, Portugal.,Faculty of Sciences, Biophysics and Biomedical Engineering, IBEB, Universidade de Lisboa, Lisboa, Portugal
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50
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A wheat germ-derived peptide YDWPGGRN facilitates skin wound-healing processes. Biochem Biophys Res Commun 2020; 524:943-950. [PMID: 32059850 DOI: 10.1016/j.bbrc.2020.01.162] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Accepted: 01/29/2020] [Indexed: 12/29/2022]
Abstract
Wheat germ derivatives have been shown to inhibit inflammation-related diseases. In this study, a small peptide (YDWPGGRN) isolated from wheat germ was used to study its anti-inflammatory activity and its application in skin wound healing. Both the in vitro and in vivo results clearly showed that YDWPGGRN significantly inhibited the LPS-stimulated NO, IL-1β, IL-6 and TNF-α production but promoted the release of an anti-inflammatory cytokine, IL-10. In addition, YDWPGGRN directly enhanced the proliferation and migration of HaCaT cells and L929 cells. Furthermore, the results demonstrated that YDWPGGRN was able to stimulate angiogenesis and collagen production in wound areas, consequently accelerating the skin wound-healing processes in a rat model with a full thickness dermal wound. The current findings suggest that YDWPGGRN promotes wound healing by anti-inflammatory reactions and enhances the proliferation and migration of keratinocytes and fibroblasts; therefore, it may be applicable for skin wound therapeutics.
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