|
1
|
Tsuchiya M, Kushibiki T, Yamashiro T, Mayumi Y, Ishihara M, Azuma R. Continuous negative-pressure wound therapy improves the survival rate of skin grafts and shortens the time required for skin graft survival. Skin Res Technol 2024; 30:e13865. [PMID: 39031918 PMCID: PMC11259545 DOI: 10.1111/srt.13865] [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: 06/16/2024] [Accepted: 06/29/2024] [Indexed: 07/22/2024]
Abstract
BACKGROUND The effectiveness of negative-pressure wound therapy (NPWT) in skin graft fixation has been demonstrated in several clinical studies. However, in vitro and in vivo studies on skin graft fixation with NPWT have been scarce. In this in vivo study, we aimed to determine whether NPWT fixation enhances skin graft survival and how it contributes to improving skin graft survival biologically. MATERIALS AND METHODS We harvested skin from the bilateral abdominal wall of 88 mice after anesthetizing them. Full-thickness skin grafts (FTSGs) were performed on contralateral harvest sites, and grafts were fixed using NPWT (continuous and intermittent modes), conventional compression methods, and wrapping with polyurethane foam as a control group. On days 5 and 10 of grafting, the survival rates of the FTSGs were evaluated. Immunohistopathological analysis and measurement of the expression levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2), and epidermal growth factor (EGF) were performed. RESULTS The survival rates of FTSG in the continuous NPWT group were significantly higher than those in the other groups. The number of capillaries in the dermis was significantly higher in the continuous NPWT group than in the other groups. In the wound bed, VEGF levels were significantly higher in both NPWT groups than in the other groups. CONCLUSION Continuous NPWT increases the survival rate of FTSGs and shortens the duration of skin graft survival.
Collapse
Affiliation(s)
- Masato Tsuchiya
- Department of Plastic and Reconstructive SurgeryNational Defense Medical CollegeTokorozawaSaitamaJapan
| | - Toshihiro Kushibiki
- Department of Medical EngineeringNational Defense Medical CollegeTokorozawaSaitamaJapan
| | - Toshifumi Yamashiro
- Department of Plastic and Reconstructive SurgeryNational Defense Medical CollegeTokorozawaSaitamaJapan
| | - Yoshine Mayumi
- Department of Medical EngineeringNational Defense Medical CollegeTokorozawaSaitamaJapan
| | - Miya Ishihara
- Department of Medical EngineeringNational Defense Medical CollegeTokorozawaSaitamaJapan
| | - Ryuichi Azuma
- Department of Plastic and Reconstructive SurgeryNational Defense Medical CollegeTokorozawaSaitamaJapan
| |
Collapse
|
|
2
|
Allen D, Mann S, Robinson T, Schmidt M, Kieswetter K. Preclinical Assessments of a Novel Peel and Place Extended-Wear Negative-Pressure Wound Therapy Dressing for up to 35 Days in a Porcine Model. Adv Wound Care (New Rochelle) 2024; 13:291-307. [PMID: 38205649 DOI: 10.1089/wound.2023.0096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2024] Open
Abstract
Objective: While the use of negative pressure wound therapy (NPWT) with reticulated open cell foam (ROCF) is well established, the characteristics of ROCF do not allow for extended-wear use. There is the potential for dressing tissue ingrowth if left in place for greater than the recommended 2-3 days. An easy to use, novel peel and place dressing has been designed for extended wear with the wound management advantages of ROCF while alleviating the challenges of tissue ingrowth. Approach: Paraspinal, full-thickness or deep muscle excisional wounds were created in 11 and 2 swine, respectively, dressings applied with continuous negative pressure at -125 mmHg, and dressings changed weekly. Full-thickness excisional wounds were treated for 13 days and deep muscle wounds for 35 days. Wound dimensions were assessed. Granulation tissue thickness and re-epithelialization were measured via digital morphometry. Tissue quality, fibrinous material prevalence, and dressing removal peel force were analyzed. Results: The peel and place dressing substantially reduces dressing tissue ingrowth, is easy to remove with markedly low dressing peel force and promotes more granulation tissue at day 13 than ROCF with an interface layer. The extended-wear peel and place dressing, when applied to deep muscle wounds with weekly dressing changes, was applied for a total of 35 days. Successful wound closure was evident without any negative impact on wound healing. Innovation: This study assessed the wound management capabilities of an extended-wear peel and place NPWT dressing used until wound closure. Conclusion: The peel and place dressing is a suitable extended-wear NPWT dressing.
Collapse
Affiliation(s)
- Diwi Allen
- Medical Solutions Division, 3M Health Care, San Antonio, Texas, USA
| | - Samantha Mann
- Medical Solutions Division, 3M Health Care, San Antonio, Texas, USA
| | - Timothy Robinson
- Medical Solutions Division, 3M Health Care, San Antonio, Texas, USA
| | - Marisa Schmidt
- Medical Solutions Division, 3M Health Care, San Antonio, Texas, USA
| | | |
Collapse
|
|
3
|
Mascharak S, Guo JL, Griffin M, Berry CE, Wan DC, Longaker MT. Modelling and targeting mechanical forces in organ fibrosis. NATURE REVIEWS BIOENGINEERING 2024; 2:305-323. [PMID: 39552705 PMCID: PMC11567675 DOI: 10.1038/s44222-023-00144-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 11/09/2023] [Indexed: 11/19/2024]
Abstract
Few efficacious therapies exist for the treatment of fibrotic diseases, such as skin scarring, liver cirrhosis and pulmonary fibrosis, which is related to our limited understanding of the fundamental causes and mechanisms of fibrosis. Mechanical forces from cell-matrix interactions, cell-cell contact, fluid flow and other physical stimuli may play a central role in the initiation and propagation of fibrosis. In this Review, we highlight the mechanotransduction mechanisms by which various sources of physical force drive fibrotic disease processes, with an emphasis on central pathways that may be therapeutically targeted to prevent and reverse fibrosis. We then discuss engineered models of mechanotransduction in fibrosis, as well as molecular and biomaterials-based therapeutic approaches for limiting fibrosis and promoting regenerative healing phenotypes in various organs. Finally, we discuss challenges within fibrosis research that remain to be addressed and that may greatly benefit from next-generation bioengineered model systems.
Collapse
Affiliation(s)
- Shamik Mascharak
- Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA
- Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA
- These authors contributed equally: Shamik Mascharak, Jason L. Guo, Michelle Griffin
| | - Jason L. Guo
- Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA
- Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA
- These authors contributed equally: Shamik Mascharak, Jason L. Guo, Michelle Griffin
| | - Michelle Griffin
- Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA
- Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA
- These authors contributed equally: Shamik Mascharak, Jason L. Guo, Michelle Griffin
| | - Charlotte E. Berry
- Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Derrick C. Wan
- Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Michael T. Longaker
- Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA
- Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA
| |
Collapse
|
|
4
|
Sexton FC, Soh V, Yahya MS, Healy DA. Effectiveness of negative-pressure wound therapy to standard therapy in the prevention of complications after vascular surgery. Minerva Surg 2024; 79:48-58. [PMID: 37930087 DOI: 10.23736/s2724-5691.23.10096-7] [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: 11/07/2023]
Abstract
Wound complications are common after vascular surgery and many may be preventable. Negative pressure wound therapy (NPWT) dressings may be able to reduce wound complications relating to closed incisions following vascular surgery and several devices are currently available along with a large body of literature. This review article will describe the use of NPWT dressings in vascular surgery. We will summarize the currently available systems, the likely mechanism of action of NWPT, the published studies to date and we will give our recommendations regarding the priorities for future research on this topic.
Collapse
Affiliation(s)
- Fiona C Sexton
- Department of Dermatology, Beaumont Hospital, Dublin, Ireland
| | - Vernie Soh
- Department of Vascular Surgery, Belfast Health and Social Care Trust, Belfast, UK
| | - Muhammad S Yahya
- Department of Vascular Surgery, Belfast Health and Social Care Trust, Belfast, UK
| | - Donagh A Healy
- Department of Vascular Surgery, Belfast Health and Social Care Trust, Belfast, UK -
| |
Collapse
|
|
5
|
Ravindhran B, Schafer N, Howitt A, Carradice D, Smith G, Chetter I. Molecular mechanisms of action of negative pressure wound therapy: a systematic review. Expert Rev Mol Med 2023; 25:e29. [PMID: 37853784 DOI: 10.1017/erm.2023.24] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2023]
Abstract
Negative pressure wound therapy (NPWT) has significantly advanced wound care and continues to find new applications. Its effects at a molecular level however, remain a subject of debate. The aim of this systematic review is to summarize the current evidence regarding the molecular mechanisms of action of NPWT. Medline, Embase, EBSCO databases and clinical trial registries were searched from inception to January 2023. Clinical studies, animal models or in-vitro studies that quantitatively or semi-quantitatively evaluated the influence of NPWT on growth factors, cytokine or gene-expression in the circulation or wound-bed were included. Risk of Bias assessment was performed using the RoBANS tool for non-randomized studies, the COCHRANE's Risk of Bias 2(ROB-2) tool for randomized clinical studies, OHAT tool for in-vitro studies or the SYRCLE tool for animal model studies. A descriptive summary was collated and the aggregated data is presented as a narrative synthesis. This review included 19 clinical studies, 11 animal studies and 3 in-vitro studies. The effects of NPWT on 43 biomarkers and 17 gene expressions were studied across included studies. NPWT stimulates modulation of numerous local and circulating cytokines and growth factor expressions to promote an anti-inflammatory profile. This is most likely achieved by downregulation of TNFα, upregulation of VEGF, TGF-β and fibronectin.
Collapse
Affiliation(s)
- Bharadhwaj Ravindhran
- Academic Vascular Surgical Unit, Hull Royal Infirmary, Hull, UK
- Department of Health Sciences, University of York, York, UK
| | - Nicole Schafer
- Academic Vascular Surgical Unit, Hull Royal Infirmary, Hull, UK
| | - Annabel Howitt
- Academic Vascular Surgical Unit, Hull Royal Infirmary, Hull, UK
| | | | - George Smith
- Academic Vascular Surgical Unit, Hull Royal Infirmary, Hull, UK
| | - Ian Chetter
- Academic Vascular Surgical Unit, Hull Royal Infirmary, Hull, UK
| |
Collapse
|
|
6
|
Hassan N, Krieg T, Zinser M, Schröder K, Kröger N. An Overview of Scaffolds and Biomaterials for Skin Expansion and Soft Tissue Regeneration: Insights on Zinc and Magnesium as New Potential Key Elements. Polymers (Basel) 2023; 15:3854. [PMID: 37835903 PMCID: PMC10575381 DOI: 10.3390/polym15193854] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 09/13/2023] [Accepted: 09/18/2023] [Indexed: 10/15/2023] Open
Abstract
The utilization of materials in medical implants, serving as substitutes for non-functional biological structures, supporting damaged tissues, or reinforcing active organs, holds significant importance in modern healthcare, positively impacting the quality of life for millions of individuals worldwide. However, certain implants may only be required temporarily to aid in the healing process of diseased or injured tissues and tissue expansion. Biodegradable metals, including zinc (Zn), magnesium (Mg), iron, and others, present a new paradigm in the realm of implant materials. Ongoing research focuses on developing optimized materials that meet medical standards, encompassing controllable corrosion rates, sustained mechanical stability, and favorable biocompatibility. Achieving these objectives involves refining alloy compositions and tailoring processing techniques to carefully control microstructures and mechanical properties. Among the materials under investigation, Mg- and Zn-based biodegradable materials and their alloys demonstrate the ability to provide necessary support during tissue regeneration while gradually degrading over time. Furthermore, as essential elements in the human body, Mg and Zn offer additional benefits, including promoting wound healing, facilitating cell growth, and participating in gene generation while interacting with various vital biological functions. This review provides an overview of the physiological function and significance for human health of Mg and Zn and their usage as implants in tissue regeneration using tissue scaffolds. The scaffold qualities, such as biodegradation, mechanical characteristics, and biocompatibility, are also discussed.
Collapse
Affiliation(s)
- Nourhan Hassan
- Department of Plastic, Reconstructive and Aesthetic Surgery, Faculty of Medicine, University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany
- Biotechnology Department, Faculty of Science, Cairo University, Giza 12613, Egypt
| | - Thomas Krieg
- Translational Matrix Biology, Medical Faculty, University of Cologne, 50923 Cologne, Germany
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50923 Cologne, Germany
- Center for Molecular Medicine (CMMC), University of Cologne, 50923 Cologne, Germany
| | - Max Zinser
- Department of Plastic, Reconstructive and Aesthetic Surgery, Faculty of Medicine, University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany
- Department for Oral and Craniomaxillofacial and Plastic Surgery, University of Cologne, Kerpener Strasse 62, 50931 Cologne, Germany
| | - Kai Schröder
- Department of Plastic, Reconstructive and Aesthetic Surgery, Faculty of Medicine, University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany
| | - Nadja Kröger
- Department of Plastic, Reconstructive and Aesthetic Surgery, Faculty of Medicine, University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany
| |
Collapse
|
|
7
|
Jepsen K, Tietmann C, Martin C, Kutschera E, Jäger A, Wüllenweber P, Gaveglio L, Cardaropoli D, Sanz-Sánchez I, Fimmers R, Jepsen S. Synergy of Regenerative Periodontal Surgery and Orthodontics Improves Quality of Life of Patients with Stage IV Periodontitis: 24-Month Outcomes of a Multicenter RCT. Bioengineering (Basel) 2023; 10:695. [PMID: 37370626 PMCID: PMC10295428 DOI: 10.3390/bioengineering10060695] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 05/15/2023] [Accepted: 06/01/2023] [Indexed: 06/29/2023] Open
Abstract
In stage IV periodontitis patients with pathologic tooth migration (PTM), interdisciplinary treatment includes regenerative periodontal surgery (RPS) with an application of biomaterials and orthodontic therapy (OT) to restore function, esthetics and thereby quality of life (QoL). In a 24-month randomized trial we explored the synergy between regenerative medicine and biomechanical force application. The following methods were used: Forty-three patients had been randomized to a combined treatment comprising RPS and subsequent OT starting either 4 weeks (early OT) or 6 months (late OT) post-operatively. Clinical periodontal parameters and oral health-related QoL (GOHAI) were recorded up to 24 months. We obtained the following results: Mean clinical attachment gain (∆CAL ± SD) was significantly higher with early OT (5.96 ± 2.1 mm) versus late OT (4.65 ± 1.76 mm) (p = 0.034). Pocket closure (PPD ≤ 4 mm) was obtained in 91% of defects with early OT compared to 90% with late OT. GOHAI-scores decreased significantly from 26.1 ± 7.5 to 9.6 ± 4.7 (early OT) and 25.1 ± 7.1 to 12.7 ± 5.6 (late OT). Inconclusion, teeth severely compromised by intrabony defects and PTM can be treated successfully by RPS followed by early OT with the advantage of an overall reduced treatment time. As a result of the combined periodontal-orthodontic therapy, the oral health-related QoL of patients was significantly improved. Early stimulation of wound healing with orthodontic forces had a favorable impact on the outcomes of regenerative periodontal surgery.
Collapse
Affiliation(s)
- Karin Jepsen
- Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Welschnonnenstrasse 17, 53111 Bonn, Germany; (C.T.)
| | - Christina Tietmann
- Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Welschnonnenstrasse 17, 53111 Bonn, Germany; (C.T.)
- Private Practice for Periodontology, Krefelder Strasse 73, 52070 Aachen, Germany
| | - Conchita Martin
- BIOCRAN Research Group, University Complutense of Madrid, 28040 Madrid, Spain
| | - Eric Kutschera
- Department of Orthodontics, University of Bonn, Welschnonnenstrasse 17, 53111 Bonn, Germany
| | - Andreas Jäger
- Department of Orthodontics, University of Bonn, Welschnonnenstrasse 17, 53111 Bonn, Germany
| | - Peter Wüllenweber
- Private Practice for Orthodontics, Theaterstraße 98-102, 52062 Aachen, Germany
| | - Lorena Gaveglio
- Private Practice, Corso Galileo Ferraris 148, 10129 Turino, Italy
| | | | | | - Rolf Fimmers
- Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, 53127 Bonn, Germany
| | - Søren Jepsen
- Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Welschnonnenstrasse 17, 53111 Bonn, Germany; (C.T.)
| |
Collapse
|
|
8
|
Wu M, Matar DY, Yu Z, Chen Z, Knoedler S, Ng B, Darwish O, Haug V, Friedman L, Orgill DP, Panayi AC. Modulation of Lymphangiogenesis in Incisional Murine Diabetic Wound Healing Using Negative Pressure Wound Therapy. Adv Wound Care (New Rochelle) 2023. [PMID: 36424821 DOI: 10.1089/wound.2022.0074] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Objective: Despite the significant function of lymphatics in wound healing, and frequent clinical use of Negative Pressure Wound Therapy (NPWT), the effect of mechanical force application on lymphangiogenesis remains to be elucidated. We utilize a murine incisional wound healing model to assess the mechanisms of lymphangiogenesis following NPWT. Approach: Dorsal incisional skin wounds were created on diabetic mice (genetically obese leptin receptor-deficient mice [db/db]; n = 30) and covered with an occlusive dressing (Control, n = 15) or NPWT (-125 mmHg, continuous, 24 h for 7 days; NPWT, n = 15). The wounds were macroscopically assessed for 28 days. Tissue was harvested on day 10 for analysis. Qualitative functional analysis of lymphatic drainage was performed on day 28 using Evans Blue staining (n = 2). Results: NPWT increased lymphatic vessel density (40 ± 20 vs. 12 ± 6 podoplanin [PDPN]+ and 25 ± 9 vs. 14 ± 8 lymphatic vessel endothelial receptor 1 [LYVE-1]+) and vessel diameter (28 ± 9 vs. 12 ± 2 μm). Western blotting verified the upregulation of LYVE-1 with NPWT. Leukocyte presence was higher with NPWT (22% ± 3.7% vs. 9.1% ± 4.1% lymphocyte common antigen [CD45]+) and the leukocytes were predominately B cells clustered within vessels (8.8% ± 2.5% vs. 18% ± 3.6% B-lymphocyte antigen CD20 [CD20]+). Macrophage presence was lower in the NPWT group. Lymphatic drainage was increased in the NPWT group, which exhibited greater Evans Blue positivity. Innovation: The lymphangiogenic effects take place independent of macrophage infiltration, appearing to correlate with B cell presence. Conclusion: NPWT promotes lymphangiogenesis in incisional wounds, significantly increasing the lymph vessel density and diameter. This study highlights the potential of NPWT to stimulate lymphatic drainage and wound healing of surgical incisions.
Collapse
Affiliation(s)
- Mengfan Wu
- Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.,Department of Plastic Surgery, Peking University Shenzhen Hospital, Shenzhen, China
| | - Dany Y Matar
- Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.,Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, USA
| | - Zhen Yu
- Opthalmology Department, Shenzhen Eye Hospital, Shenzhen Key Ophthalmic Laboratory, Jinan University, Shenzhen, China.,Angiogenesis Laboratory, Ophthalmology Department, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA
| | - Ziyu Chen
- Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Samuel Knoedler
- Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.,Department for Plastic Surgery and Hand Surgery, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - Brian Ng
- Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.,Department of Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA
| | - Oliver Darwish
- Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.,Department of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA
| | - Valentin Haug
- Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.,Department of Hand, Plastic and Reconstructive Surgery, Microsurgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany
| | - Leigh Friedman
- Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.,Department of Medicine, Lehigh University, Bethlehem, Pennsylvania, USA.,Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA
| | - Dennis P Orgill
- Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Adriana C Panayi
- Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.,Department of Hand, Plastic and Reconstructive Surgery, Microsurgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany
| |
Collapse
|
|
9
|
Yamashiro T, Kushibiki T, Mayumi Y, Tsuchiya M, Ishihara M, Azuma R. Negative-Pressure Wound Therapy: What We Know and What We Need to Know. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1436:131-152. [PMID: 36922487 DOI: 10.1007/5584_2023_773] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/17/2023]
Abstract
Negative-pressure wound therapy (NPWT) promotes wound healing by applying negative pressure to the wound surface. A quarter of a century after its introduction, NPWT has been used in various clinical conditions, although molecular biological evidence is insufficient due to delay in basic research. Here, we have summarized the history of NPWT, its mechanism of action, what is currently known about it, and what is expected to be known in the future. Particularly, attention has shifted from the four main mechanisms of NPWT to the accompanying secondary effects, such as effects on various cells, bacteria, and surgical wounds. This chapter will help the reader to understand the current status and shortcomings of NPWT-related research, which could aid in the development of basic research and, eventually, clinical use with stronger scientific evidence.
Collapse
Affiliation(s)
- Toshifumi Yamashiro
- Department of Plastic and Reconstructive Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Toshihiro Kushibiki
- Department of Medical Engineering, National Defense Medical College, Tokorozawa, Saitama, Japan.
| | - Yoshine Mayumi
- Department of Medical Engineering, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Masato Tsuchiya
- Department of Plastic and Reconstructive Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Miya Ishihara
- Department of Medical Engineering, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Ryuichi Azuma
- Department of Plastic and Reconstructive Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
| |
Collapse
|
|
10
|
Yamashiro T, Kushibiki T, Mayumi Y, Tsuchiya M, Ishihara M, Azuma R. Novel cell culture system for monitoring cells during continuous and variable negative-pressure wound therapy. Skin Res Technol 2023; 29:e13262. [PMID: 36704879 PMCID: PMC9838773 DOI: 10.1111/srt.13262] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 12/13/2022] [Indexed: 12/27/2022]
Abstract
BACKGROUND Although the clinical efficacy of negative-pressure wound therapy (NPWT) is well known, many of its molecular biological mechanisms remain unresolved, mainly due to the difficulty and paucity of relevant in vitro studies. We attempted to develop an in vitro cell culture system capable of real-time monitoring of cells during NPWT treatment. MATERIALS AND METHODS A novel negative-pressure cell culture system was developed by combining an inverted microscope, a stage-top incubator, a sealed metal chamber for cell culture, and an NPWT treatment device. Human keratinocytes, PSVK-1, were divided into ambient pressure (AP), continuous negative-pressure (NPc), and intermittent negative-pressure (NPi) groups and cultured for 24 h with scratch assay using our real-time monitoring system and device. Pressure inside the device, medium evaporation rate, and the residual wound area were compared across the groups. RESULTS Pressure in the device was maintained at almost the same value as set in all groups. Medium evaporation rate was significantly higher in the NPi group than in the other two groups; however, it had negligible effect on cell culture. Residual wound area after 9 h evaluated by the scratch assay was significantly smaller in the NPc and NPi groups than in the AP group. CONCLUSION We developed a negative-pressure cell culture device that enables negative-pressure cell culture under conditions similar to those used in clinical practice and is able to monitor cells under NPWT. Further experiments using this device would provide high-quality molecular biological evidence for NPWT.
Collapse
Affiliation(s)
- Toshifumi Yamashiro
- Department of Plastic and Reconstructive SurgeryNational Defense Medical CollegeTokorozawaSaitamaJapan
| | - Toshihiro Kushibiki
- Department of Medical EngineeringNational Defense Medical CollegeTokorozawaSaitamaJapan
| | - Yoshine Mayumi
- Department of Medical EngineeringNational Defense Medical CollegeTokorozawaSaitamaJapan
| | - Masato Tsuchiya
- Department of Plastic and Reconstructive SurgeryNational Defense Medical CollegeTokorozawaSaitamaJapan
| | - Miya Ishihara
- Department of Medical EngineeringNational Defense Medical CollegeTokorozawaSaitamaJapan
| | - Ryuichi Azuma
- Department of Plastic and Reconstructive SurgeryNational Defense Medical CollegeTokorozawaSaitamaJapan
| |
Collapse
|
|
11
|
Effect of Prophylactic Negative-Pressure Wound Therapy for High-Risk Wounds in Colorectal Cancer Surgery: A Randomized Controlled Trial. Adv Skin Wound Care 2022; 35:597-603. [DOI: 10.1097/01.asw.0000874168.60793.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
|
|
12
|
Mascharak S, desJardins-Park HE, Davitt MF, Guardino NJ, Gurtner GC, Wan DC, Longaker MT. Modulating Cellular Responses to Mechanical Forces to Promote Wound Regeneration. Adv Wound Care (New Rochelle) 2022; 11:479-495. [PMID: 34465219 PMCID: PMC9245727 DOI: 10.1089/wound.2021.0040] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Accepted: 08/23/2021] [Indexed: 12/13/2022] Open
Abstract
Significance: Skin scarring poses a major biomedical burden for hundreds of millions of patients annually. However, this burden could be mitigated by therapies that promote wound regeneration, with full recovery of skin's normal adnexa, matrix ultrastructure, and mechanical strength. Recent Advances: The observation of wound regeneration in several mouse models suggests a retained capacity for postnatal mammalian skin to regenerate under the right conditions. Mechanical forces are a major contributor to skin fibrosis and a prime target for devices and therapeutics that could promote skin regeneration. Critical Issues: Wound-induced hair neogenesis, Acomys "spiny" mice, Murphy Roths Large mice, and mice treated with mechanotransduction inhibitors all show various degrees of wound regeneration. Comparison of regenerating wounds in these models against scarring wounds reveals differences in extracellular matrix interactions and in mechanosensitive activation of key signaling pathways, including Wnt, Sonic hedgehog, focal adhesion kinase, and Yes-associated protein. The advent of single-cell "omics" technologies has deepened this understanding and revealed that regeneration may recapitulate development in certain contexts, although it is unknown whether these mechanisms are relevant to healing in tight-skinned animals such as humans. Future Directions: While early findings in mice are promising, comparison across model systems is needed to resolve conflicting mechanisms and to identify conserved master regulators of skin regeneration. There also remains a dire need for studies on mechanomodulation of wounds in large, tight-skinned animals, such as red Duroc pigs, which better approximate human wound healing.
Collapse
Affiliation(s)
- Shamik Mascharak
- Division of Plastic and Reconstructive Surgery, Department of Surgery; Stanford, California, USA
- Institute for Stem Cell Biology and Regenerative Medicine; Stanford University School of Medicine, Stanford, California, USA
| | - Heather E. desJardins-Park
- Division of Plastic and Reconstructive Surgery, Department of Surgery; Stanford, California, USA
- Institute for Stem Cell Biology and Regenerative Medicine; Stanford University School of Medicine, Stanford, California, USA
| | - Michael F. Davitt
- Division of Plastic and Reconstructive Surgery, Department of Surgery; Stanford, California, USA
| | - Nicholas J. Guardino
- Division of Plastic and Reconstructive Surgery, Department of Surgery; Stanford, California, USA
| | - Geoffrey C. Gurtner
- Division of Plastic and Reconstructive Surgery, Department of Surgery; Stanford, California, USA
| | - Derrick C. Wan
- Division of Plastic and Reconstructive Surgery, Department of Surgery; Stanford, California, USA
| | - Michael T. Longaker
- Division of Plastic and Reconstructive Surgery, Department of Surgery; Stanford, California, USA
- Institute for Stem Cell Biology and Regenerative Medicine; Stanford University School of Medicine, Stanford, California, USA
| |
Collapse
|
|
13
|
Zhang H, Wang S, Lei C, Li G, Wang B. Experimental study of negative pressure wound therapy combined with platelet-rich fibrin for bone-exposed wounds. Regen Med 2021; 17:23-35. [PMID: 34905932 DOI: 10.2217/rme-2021-0043] [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: 11/21/2022] Open
Abstract
Aim: To evaluate the efficacy of negative pressure wound therapy (NPWT) combined with platelet-rich fibrin (PRF) in treating bone-exposed wounds and explore its possible mechanism. Materials & methods: A bone-exposed wound was created in a total of 32 healthy Sprague-Dawley rats, which were divided into either control group, NPWT group, PRF group or both (N + P group). The bone-exposed area, skin contraction rate and granulation coverage and the level of growth factors in granulation tissue were determined on days 4, 7 and 10. Results: The N + P group showed significantly higher wound closure rate than that achieved with others respectively. Four factors were significantly higher in N + P group than in the other three groups. Conclusion: Combination of NPWT and PRF can repair bone-exposed wounds effectively and accelerate wound healing.
Collapse
Affiliation(s)
- Hong Zhang
- Department of Plastic & Cosmetic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou Fujian, 350000, PR China.,Department of Pediatric Surgery, Fujian Children's Hospital, Fuzhou Fujian, 350000, PR China.,Fujian Branch of Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Fuzhou Fujian, 350000, PR China.,Fujian Maternity & Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou Fujian, 350000, PR China
| | - Songyu Wang
- Department of Plastic & Cosmetic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou Fujian, 350000, PR China
| | - Chen Lei
- Department of Plastic & Cosmetic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou Fujian, 350000, PR China
| | - Guanmin Li
- Department of Plastic & Cosmetic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou Fujian, 350000, PR China
| | - Biao Wang
- Department of Plastic & Cosmetic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou Fujian, 350000, PR China
| |
Collapse
|
|
14
|
Abstract
PRACTICAL RELEVANCE Open wounds and their treatment present a common challenge in veterinary practice. Approaching 15 years ago negative pressure wound therapy (NPWT) started to be incorporated into clinical veterinary medicine, and its availability is becoming more widespread in Europe and the USA. Use of this therapy has the potential to significantly increase the healing rate of open wounds as well as free skin grafts in small animals, and it has been occasionally described for the management of feline wounds. AIM This review describes the mechanisms of action of, and indications for, NPWT, and offers recommendations for NPWT specific to feline patients. EVIDENCE BASE The information presented is based on the current evidence and the author's clinical experience of the technique gained over the past 12 years. Comparative studies of different treatment options are lacking and, since wound healing in cats and dogs differs, cat-specific studies are especially needed. Well-designed wound healing studies comparing different advanced techniques will improve open wound healing in cats in the future, and potentially allow better understanding of the role of NPWT in this setting.
Collapse
Affiliation(s)
- Mirja C Nolff
- Clinic for Small Animal Surgery, Tierspital Zürich, University of Zürich, Winterthurerstrasse 260, 8057 Zürich, Switzerland
| |
Collapse
|
|
15
|
Li Y, Sun Y, Liu Z, Li Y, Gou S. Active drain system with reticulated open-pore foam-surface dressing for postoperative pancreatic fistula in a rat model. Ann Med Surg (Lond) 2021; 68:102559. [PMID: 34386219 PMCID: PMC8346361 DOI: 10.1016/j.amsu.2021.102559] [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: 05/31/2021] [Accepted: 07/10/2021] [Indexed: 02/07/2023] Open
Abstract
Background Postoperative pancreatic fistula (POPF) is one of the most harmful complications after pancreatic resection. Efficient drainage affects the clinical outcome of POPF. Inefficient drain of the fluid collection should contribute greatly to the need of additional interventional drainage, secondary morbid complications, and death. Methods A rat model of POPF was established by distal pancreatosplenectomy. A novel active drain system (ADS) for POPF was developed by wrapping polyvinyl alcohol sponges (PVA) to an end of the drainage tube. Passive drain system (PDS), ADS and ADS with PVA were used for POPF in rat models. The volume and amylase of ascites were measured. CT scan was applied to assess abdominal fluid collection. Rats pancreatic transection stumps were stained by hematoxylin and eosin (H&E). Results The volume of drainage of ADS with PVA group was less than that of PDS group and ADS group at late stage. CT scan showed obvious abdominal fluid collections in 2/8, 2/8 and 0/8 rats in PDS, ADS and ADS with PVA group separately. Macrofindings showed significant intra-abdominal adhesions and inflammation in PDS and ADS group but not in ADS with PVA group. H&E staining showed less inflammatory cells and destroyed pancreatic glands in ADS with PVA group. Conclusion ADS with PVA drained ascites effectively in the rat model of POPF. The effective drainage of pancreatic juice reduced the inflammation of abdominal organs and pancreatic resection stumps, and might promote the healing of POPF.
Collapse
Affiliation(s)
- Yang Li
- Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Ying Sun
- Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zhiqiang Liu
- Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yongfeng Li
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Shanmiao Gou
- Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| |
Collapse
|
|
16
|
Notorgiacomo G, Klug J, Rapp S, Boyce ST, Schutte SC. A bioreactor for studying negative pressure wound therapy on skin grafts. Int Wound J 2021; 19:633-642. [PMID: 34235863 PMCID: PMC8874041 DOI: 10.1111/iwj.13661] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 06/25/2021] [Accepted: 06/29/2021] [Indexed: 12/01/2022] Open
Abstract
Negative pressure wound therapy (NPWT) has become the prevailing standard of care for treating complex soft tissue wounds and is now being considered for use in alternative applications including improving skin graft take. While it is generally agreed that negative pressure leads to improved wound healing, universal consensus on its optimal application is not supported in the literature. We describe the design and validation of a bioreactor to determine the prospective benefits of NPWT on skin grafts and engineered skin substitutes (ESS). Clinically relevant pressures were applied, and the native human skin was able to withstand greater negative pressures than the engineered substitutes. Both skin types were cultured under static, flow‐only, and −75 mm Hg conditions for 3 days. While it remained intact, there was damage to the epidermal‐dermal junction in the ESS after application of negative pressure. The normal skin remained viable under all culture conditions. The engineered skin underwent apoptosis in the flow‐only group; however, the application of negative pressure reduced apoptosis. Vascular endothelial growth factor levels were significantly higher in the normal flow‐only group, 152.0 ± 75.1 pg/mg protein, than the other culture conditions, 81.6 ± 35.5 pg/mg for the static and 103.6 ± pg/mg for the negative pressure conditions. The engineered skin had a similar trend but the differences were not significant. This bioreactor design can be used to evaluate the impacts of NPWT on the anatomy and physiology of skin to improve outcomes in wounds after grafting with normal or engineered skin.
Collapse
Affiliation(s)
| | - Justin Klug
- Department of Biomedical Engineering, University of Cincinnati, Cincinnati, Ohio, USA
| | - Scott Rapp
- Division of Plastic Surgery, Norton Children's Hospital, Louisville, Kentucky, USA.,Kentucky Center for Cosmetic and Reconstructive Surgery, Louisville, Kentucky, USA.,Research Department, Shriners Hospitals for Children-Cincinnati, Cincinnati, Ohio, USA
| | - Steven T Boyce
- Research Department, Shriners Hospitals for Children-Cincinnati, Cincinnati, Ohio, USA.,Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA
| | - Stacey C Schutte
- Department of Biomedical Engineering, University of Cincinnati, Cincinnati, Ohio, USA.,Research Department, Shriners Hospitals for Children-Cincinnati, Cincinnati, Ohio, USA
| |
Collapse
|
|
17
|
Zhu J, Wang F, Yan L, Wang J, Wu M, Hu R, An Y. Negative pressure wound therapy enhances bone regeneration compared with conventional therapy in a rabbit radius gap-healing model. Exp Ther Med 2021; 21:474. [PMID: 33767769 PMCID: PMC7976378 DOI: 10.3892/etm.2021.9905] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Accepted: 10/14/2020] [Indexed: 12/11/2022] Open
Abstract
Negative pressure wound therapy (NPWT) has been recognized as an effective method for the treatment of intractable wounds. However, its effects on bone healing remain to be elucidated. Our previous study demonstrated that NPWT induced cell proliferation and osteoblastic differentiation of rat periosteum-derived mesenchymal stem cells (P-MSCs). It was reported that following NPWT treatment, the expression of the mechanotransduction molecule integrin β5 is increased, indicating that NPWT may serve an active role in fracture healing by enhancing bone formation and reducing bone resorption. The present study sought to further investigate the efficacy of NPWT on the bone regeneration process in a rabbit radial gap-healing model. All rabbits with radial defects were randomly divided into two groups: NPWT and control groups. Continuous negative pressure at -125 mmHg was applied to all rabbits. Furthermore, X-ray imaging and scoring on day 7, 14, 21 and 28 postoperatively were performed to evaluate new bone formation. Histological changes were determined via hematoxylin and eosin and Masson's trichrome staining at 2- and 4-weeks following surgery. In addition, vimentin-positive cells located in the periosteum were detected via immunohistochemical examination on day 3 post operation. Finally, protein expression levels of vascular endothelial growth factor (VEGF), bone morphogenetic protein (BMP)-2 and osteopontin (OPN) were evaluated using western blot analysis on the 2nd and 4th week following NPWT. X-ray and histological examination revealed that the bone-healing processes in the NPWT group were faster compared with the control group. Additionally, compared with the control group, the NPWT group exhibited higher X-ray scores, increased percentage of positive vimentin-stained cells and upregulated expression of VEGF, BMP-2 and OPN proteins. The aforementioned findings suggest that NPWT, under a continuous negative pressure of -125 mmHg, may accelerate bone regeneration by enhancing MSC proliferation, osteoblastic differentiation and VEGF, BMP-2 and OPN expression.
Collapse
Affiliation(s)
- Jin Zhu
- Department of Orthopedics, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China
| | - Fangfang Wang
- Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China
| | - Li Yan
- Department of Orthopedics, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China
| | - Junwen Wang
- Department of Orthopedics, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China
| | - Mingzheng Wu
- Department of Orthopedics, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China
| | - Rui Hu
- Department of Orthopedics, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China
| | - Ying An
- Department of Orthopedics, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China
| |
Collapse
|
|
18
|
Preconditioning with Foam-mediated External Suction on Flap Microvasculature and Perfusion in a Rodent Model. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2020; 8:e2739. [PMID: 32983749 PMCID: PMC7489611 DOI: 10.1097/gox.0000000000002739] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 01/31/2020] [Indexed: 12/16/2022]
Abstract
Foam-mediated external suction (FMES) has previously shown to improve tissue microcirculation. We hypothesized that preconditioning fasciocutaneous perforator flaps with FMES would augment perfusion and demonstrate greater capillary recruitment.
Collapse
|
|
19
|
Geierlehner A, Horch RE, Müller-Seubert W, Arkudas A, Ludolph I. Limb salvage procedure in immunocompromised patients with therapy-resistant leg ulcers-The value of ultra-radical debridement and instillation negative-pressure wound therapy. Int Wound J 2020; 17:1496-1507. [PMID: 32573103 PMCID: PMC7948940 DOI: 10.1111/iwj.13428] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 05/21/2020] [Accepted: 05/25/2020] [Indexed: 01/05/2023] Open
Abstract
The purpose of this study was to analyse the outcome of our established triple treatment strategy in therapy‐resistant deep‐thickness chronic lower leg ulcers. This limb salvage approach consists of ultra‐radical surgical debridement, negative‐pressure wound therapy (NPWT) with or without instillation, and split‐thickness skin grafting. Between March 2003 and December 2019, a total of 16 patients and 24 severe cases of lower leg ulcers were eligible for inclusion in this highly selective population. A total of seven patients received immunosuppressive medication. Complete wound closure was achieved in 25% and almost 90% of included lower leg ulcer cases after 3 and 24 months of our triple treatment strategy, respectively. The overall limb salvage rate was 100%. Bacterial colonisation of these wounds was significantly reduced after multiple surgical debridements and NPWT. Fasciotomy and radical removal of devitalised tissue such as deep fascia, tendons, and muscles combined with NPWT showed promising results in terms of the overall graft take rate. This treatment strategy was considered as last resort for limb salvage in such a critically ill and immunocompromised patient population. Surgeons should be aware of its efficacy and consider the triple treatment strategy especially if no other limb salvage option remains.
Collapse
Affiliation(s)
- Alexander Geierlehner
- Department of Plastic and Hand Surgery, Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuernberg (FAU), Erlangen, Germany
| | - Raymund E Horch
- Department of Plastic and Hand Surgery, Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuernberg (FAU), Erlangen, Germany
| | - Wibke Müller-Seubert
- Department of Plastic and Hand Surgery, Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuernberg (FAU), Erlangen, Germany
| | - Andreas Arkudas
- Department of Plastic and Hand Surgery, Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuernberg (FAU), Erlangen, Germany
| | - Ingo Ludolph
- Department of Plastic and Hand Surgery, Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuernberg (FAU), Erlangen, Germany
| |
Collapse
|
|
20
|
Cui HS, Joo SY, Cho YS, Park JH, Kim JB, Seo CH. Effect of Combining Low Temperature Plasma, Negative Pressure Wound Therapy, and Bone Marrow Mesenchymal Stem Cells on an Acute Skin Wound Healing Mouse Model. Int J Mol Sci 2020; 21:E3675. [PMID: 32456187 PMCID: PMC7279345 DOI: 10.3390/ijms21103675] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 05/11/2020] [Accepted: 05/21/2020] [Indexed: 12/24/2022] Open
Abstract
Low-temperature plasma (LTP; 3 min/day), negative pressure wound therapy (NPWT; 4 h/day), and bone marrow mesenchymal stem cells (MSCs; 1×106 cells/day) were used as mono- and combination therapy in an acute excisional skin wound-healing ICR mouse model. These therapies have been beneficial in treating wounds. We investigated the effectiveness of monotherapy with LTP, NPWT, and MSC and combination therapy with LTP + MSC, LTP + NPWT, NPWT + MSC, and LTP + NPWT + MSC on skin wounds in mice for seven consecutive days. Gene expression, protein expression, and epithelial thickness were analyzed using real time polymerase chain reaction (RT-qPCR), western blotting, and hematoxylin and eosin staining (H&E), respectively. Wound closure was also evaluated. Wound closure was significantly accelerated in monotherapy groups, whereas more accelerated in combination therapy groups. Tumor necrosis factor-α (TNF-α) expression was increased in the LTP monotherapy group but decreased in the NPWT, MSC, and combination therapy groups. Expressions of vascular endothelial growth factor (VEGF), α-smooth muscle actin (α-SMA), and type I collagen were increased in the combination therapy groups. Re-epithelialization was also considerably accelerated in combination therapy groups. Our findings suggest that combination therapy with LPT, NPWT, and MSC exert a synergistic effect on wound healing, representing a promising strategy for the treatment of acute wounds.
Collapse
Affiliation(s)
- Hui Song Cui
- Burn Institute, Department of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Korea; (H.S.C.); (J.H.P.)
| | - So Young Joo
- Department of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Korea; (S.Y.J.); (Y.S.C.)
| | - Yoon Soo Cho
- Department of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Korea; (S.Y.J.); (Y.S.C.)
| | - Ji Heon Park
- Burn Institute, Department of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Korea; (H.S.C.); (J.H.P.)
| | - June-Bum Kim
- Department of Pediatrics, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Korea
| | - Cheong Hoon Seo
- Department of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Korea; (S.Y.J.); (Y.S.C.)
| |
Collapse
|
|
21
|
Rennekampff HO, Tenenhaus M. Theoretical basis for optimal surgical incision planning to reduce hypertrophic scar formation. Med Hypotheses 2020; 140:109672. [PMID: 32197119 DOI: 10.1016/j.mehy.2020.109672] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Revised: 02/29/2020] [Accepted: 03/10/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND After approximately 24 weeks of gestation, human cutaneous wounds and incisions heal by scar formation. Continued or unregulated stimulation of tissue fibroblasts is thought to lead to an activated state with ongoing collagen deposition resulting in a visible hypertrophic scar. There is evidence that mechanical forces as sensed by fibroblasts lead to downstream events such as excessive extracellular matrix deposition. Mechanical forces acting on the wound fibroblast are exerted by underlying muscles as well as intrinsic forces found in the dermal component of the surrounding skin. Under static conditions, collagen is oriented parallel to the direction of strain. In an effort to minimize resultant scar formation various and often contradictory lines of non-extension, lines of least tension, have been described for planning optimal surgical incisions. HYPOTHESIS We hypothesize that it is possible to avoid longitudinal stretch on incisions and thereby minimize resultant pathologic scars if defined anatomical considerations are respected. We hypothesize that placement of skin incisions parallel to lines of minimal longitudinal stretch, non-invasively measured by orientation of collagen orientation would in turn result in minimal scar formation. EVIDENCE Historical recommendations often derived from human post mortem studies and animal experiments have shed some light on cutaneously observed lines of non-extension. Theoretical considerations of non-extension lines have suggested possible directions of surgical incisions. Post surgical analysis of dermatological interventions have similarly added to our understanding of possible non-extension lines. Measuring anisotropy in the skin can determine collagen orientation in the skin and may therefore allow one to objectively place incisions parallel to non-extension lines. To date no randomized clinical study in humans has addressed whether such an approach would lead to less scarring. A study involving volunteers examining many body areas seems ethically challenged. CONCLUSION The hypothesis, although not proven, is supported by available evidence. If our hypothesis that measurable cutaneous collagen orientation guided incisions improved scar formation then surgical incision planning would deservedly require more clinical attention. Preoperative measurement or at least pre-closure assessment of anisotropy prior to surgical incision placement or closure would notably reduce the incidence of hypertrophic scars.
Collapse
Affiliation(s)
- H O Rennekampff
- Dept of Plastic Surgery, Hand and Burn Surgery, RheinMaas Klinikum, Aachen/Wuerselen, Germany.
| | - M Tenenhaus
- Dept of Plastic Surgery, Hand and Burn Surgery, RheinMaas Klinikum, Aachen/Wuerselen, Germany
| |
Collapse
|
|
22
|
Horch RE, Ludolph I, Müller-Seubert W, Zetzmann K, Hauck T, Arkudas A, Geierlehner A. Topical negative-pressure wound therapy: emerging devices and techniques. Expert Rev Med Devices 2020; 17:139-148. [PMID: 31920139 DOI: 10.1080/17434440.2020.1714434] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Introduction: The treatment of chronic wounds constitutes a massive financial burden to society and our health-care system. Therefore, efficient wound care is of great importance to all kinds of medical fields. The implementation and modification of negative-pressure wound therapy can be seen as a major improvement in wound healing. Many different NPWT applications evolved trying to address various wound etiologies.Areas covered: This review aims to give an overview of various NPWT applications, show its effects on wound healing, and discuss future modifications.Expert opinion: NPWT as a delivery device for cold plasma, growth factors, or targeted stem cells to the wound bed and the ability to monitor the inflammatory activity, bacterial load and wound healing factors can be seen as possible future steps to individualized wound care. In addition, it requires high-quality experimental studies to develop the ideal foam in terms of microstructure, pore size, and material properties.
Collapse
Affiliation(s)
- Raymund E Horch
- Department of Plastic and Hand Surgery, Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuernberg FAU, Erlangen, Germany
| | - Ingo Ludolph
- Department of Plastic and Hand Surgery, Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuernberg FAU, Erlangen, Germany
| | - Wibke Müller-Seubert
- Department of Plastic and Hand Surgery, Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuernberg FAU, Erlangen, Germany
| | - Katharina Zetzmann
- Department of Plastic and Hand Surgery, Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuernberg FAU, Erlangen, Germany
| | - Theresa Hauck
- Department of Plastic and Hand Surgery, Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuernberg FAU, Erlangen, Germany
| | - Andreas Arkudas
- Department of Plastic and Hand Surgery, Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuernberg FAU, Erlangen, Germany
| | - Alexander Geierlehner
- Department of Plastic and Hand Surgery, Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuernberg FAU, Erlangen, Germany
| |
Collapse
|
|
23
|
Meli VS, Veerasubramanian PK, Atcha H, Reitz Z, Downing TL, Liu WF. Biophysical regulation of macrophages in health and disease. J Leukoc Biol 2019; 106:283-299. [PMID: 30861205 PMCID: PMC7001617 DOI: 10.1002/jlb.mr0318-126r] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Macrophages perform critical functions for homeostasis and immune defense in tissues throughout the body. These innate immune cells are capable of recognizing and clearing dead cells and pathogens, and orchestrating inflammatory and healing processes that occur in response to injury. In addition, macrophages are involved in the progression of many inflammatory diseases including cardiovascular disease, fibrosis, and cancer. Although it has long been known that macrophages respond dynamically to biochemical signals in their microenvironment, the role of biophysical cues has only recently emerged. Furthermore, many diseases that involve macrophages are also characterized by changes to the tissue biophysical environment. This review will discuss current knowledge about the effects of biophysical cues including matrix stiffness, material topography, and applied mechanical forces, on macrophage behavior. We will also describe the role of molecules that are known to be important for mechanotransduction, including adhesion molecules, ion channels, as well as nuclear mediators such as transcription factors, scaffolding proteins, and epigenetic regulators. Together, this review will illustrate a developing role of biophysical cues in macrophage biology, and also speculate upon molecular targets that may potentially be exploited therapeutically to treat disease.
Collapse
Affiliation(s)
- Vijaykumar S. Meli
- Department of Biomedical Engineering, University of California Irvine, CA 92697
- The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, CA 92697
| | - Praveen K. Veerasubramanian
- Department of Biomedical Engineering, University of California Irvine, CA 92697
- The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, CA 92697
| | - Hamza Atcha
- Department of Biomedical Engineering, University of California Irvine, CA 92697
- The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, CA 92697
| | - Zachary Reitz
- Department of Biomedical Engineering, University of California Irvine, CA 92697
- The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, CA 92697
| | - Timothy L. Downing
- Department of Biomedical Engineering, University of California Irvine, CA 92697
- The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, CA 92697
- Department of Microbiology and Molecular Genetics, University of California Irvine, CA 92697
| | - Wendy F. Liu
- Department of Biomedical Engineering, University of California Irvine, CA 92697
- The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, CA 92697
- Department of Chemical and Biomolecular Engineering, University of California Irvine, CA 92697
| |
Collapse
|
|
24
|
Sirisena R, Bellot GL, Puhaindran ME. The Role of Negative-Pressure Wound Therapy in Lower-Limb Reconstruction. Indian J Plast Surg 2019; 52:73-80. [PMID: 31456615 PMCID: PMC6664838 DOI: 10.1055/s-0039-1687922] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Negative-pressure wound therapy (NPWT) has gained increasing popularity among clinicians since its introduction in 1997 as a potential aid to wound healing. Multiple benefits of NPWT have since been proven in studies, including increase in granulation tissue formation, decrease in bacterial load, and the improved survival of flaps. With our increasing use and greater understanding of the tissue and cellular changes that occur in a wound treated with NPWT, our lower-limb reconstructive practice has also evolved. Although controversial, the definite timing for lower-limb reconstruction has stretched from 72 hours to longer than 2 weeks as NPWT contains the wound within a sterile, closed system. It has also shown to decrease the rate of infection in open tibia fractures. Previously, a large number of critical defects of the lower limb would require free tissue transfer for definitive reconstruction. NPWT has reduced this rate by more than 50% and has allowed for less complicated resurfacing procedures to be performed instead.
Collapse
Affiliation(s)
- Renita Sirisena
- Department of Hand and Reconstructive Microsurgery, National University Hospital, Singapore
| | - Gregory Lucien Bellot
- Department of Hand and Reconstructive Microsurgery, National University Hospital, Singapore
| | - Mark Edward Puhaindran
- Department of Hand and Reconstructive Microsurgery, National University Hospital, Singapore
| |
Collapse
|
|
25
|
Aydin OE, Algan S, Tan O, Demirci E, Keles ON, Kantarci A. A novel method for flap delay vacuum assisted flap delay: an experimental study in rabbits. J Plast Surg Hand Surg 2019; 53:208-215. [DOI: 10.1080/2000656x.2019.1582425] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Affiliation(s)
- Osman Enver Aydin
- Faculty of Medicine, Department of Plastic, Reconstructive and Aesthetic Surgery, Adnan Menderes University, Aydin, Turkey
| | - Said Algan
- Department of Plastic, Reconstructive and Aesthetic Surgery, Medical Park Hospital, Batman, Turkey
| | - Onder Tan
- Faculty of Medicine, Department of Plastic Reconstructive and Aesthetic Surgery, Ataturk University, Burn Care Ward, Erzurum, Turkey
| | - Elif Demirci
- Faculty of Medicine, Department of Pathology, Ataturk University, Erzurum, Turkey
| | - Osman N. Keles
- Faculty of Medicine, Department of Histology and Embryology, Ataturk University, Erzurum, Turkey
| | - Abdulmecit Kantarci
- Faculty of Medicine, Department of Radiology, Ataturk University, Erzurum, Turkey
| |
Collapse
|
|
26
|
James SMD, Sureshkumar S, Elamurugan TP, Debasis N, Vijayakumar C, Palanivel C. Comparison of Vacuum-Assisted Closure Therapy and Conventional Dressing on Wound Healing in Patients with Diabetic Foot Ulcer: A Randomized Controlled Trial. Niger J Surg 2019; 25:14-20. [PMID: 31007506 PMCID: PMC6452767 DOI: 10.4103/njs.njs_14_18] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Background: Vacuum-assisted closure (VAC) therapy has been shown to be beneficial in a variety of wounds. However, evidence of its benefit in diabetic foot ulcers (DFUs), especially with respect to Indian population, is sparse. Methodology: This randomized controlled trial included DFUs of Wagner's Grades 1 and 2. Patients were further stratified with respect to DFU size <10 cm and ≥10 cm. Patients with vascular disease, osteomyelitis, and bilateral DFUs were excluded from the study. The enrolled patients were randomized to receive VAC therapy or conventional dressing. The time to wound healing, granulation tissue formation, and complications such as pain, infection, and bleeding were compared between the two groups. Results: A total of sixty patients were randomized, of which 27 in each group were analyzed. The mean time to healing in days was significantly less in VAC group (22.52 vs. 3.85; P < 0.0001). Mean time to achieve 75%–100% granulation tissue cover was significantly less in VAC group (23.33 vs. 32.15; P < 0.0001). Rate of granulation tissue formation was also found to be significantly better in VAC group (2.91 cm2/day vs. 2.16 cm2/day; P = 0.0306). There was no difference between the two groups with respect to wound infection and bleeding which are commonly attributed to VAC therapy. VAC therapy group had significantly lesser pain at week 3 (Visual Analog Scale score 3 vs. 4; P = 0.004). Conclusion: VAC therapy significantly decreases the time to complete wound healing, hastens granulation tissue formation, and reduces the ulcer area compared to conventional dressing. The study did not find any significant increase in the bleeding and infection in the VAC therapy group.
Collapse
Affiliation(s)
- Sangma M D James
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Sathasivam Sureshkumar
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Thirthar P Elamurugan
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Naik Debasis
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Chellappa Vijayakumar
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Chinnakali Palanivel
- Department of Preventive and Social Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| |
Collapse
|
|
27
|
Bellot GL, Dong X, Lahiri A, Sebastin SJ, Batinic-Haberle I, Pervaiz S, Puhaindran ME. MnSOD is implicated in accelerated wound healing upon Negative Pressure Wound Therapy (NPWT): A case in point for MnSOD mimetics as adjuvants for wound management. Redox Biol 2019; 20:307-320. [PMID: 30390545 PMCID: PMC6218638 DOI: 10.1016/j.redox.2018.10.014] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Revised: 09/30/2018] [Accepted: 10/17/2018] [Indexed: 12/16/2022] Open
Abstract
Negative Pressure Wound Therapy (NPWT), a widely used modality in the management of surgical and trauma wounds, offers clear benefits over conventional wound healing strategies. Despite the wide-ranging effects ascribed to NPWT, the precise molecular mechanisms underlying the accelerated healing supported by NPWT remains poorly understood. Notably, cellular redox status-a product of the balance between cellular reactive oxygen species (ROS) production and anti-oxidant defense systems-plays an important role in wound healing and dysregulation of redox homeostasis has a profound effect on wound healing. Here we investigated potential links between the use of NPWT and the regulation of antioxidant mechanisms. Using patient samples and a rodent model of acute injury, we observed a significant accumulation of MnSOD protein as well as higher enzymatic activity in tissues upon NPWT. As a proof of concept and to outline the important role of SOD activity in wound healing, we replaced NPWT by the topical application of a MnSOD mimetic, Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP5+, MnE, BMX-010, AEOl10113) in the rodent model. We observed that MnE is a potent wound healing enhancer as it appears to facilitate the formation of new tissue within the wound bed and consequently advances wound closure by two days, compared to the non-treated animals. Taken together, these results show for the first time a link between NPWT and regulation of antioxidant mechanism through the maintenance of MnSOD activity. Additionally this discovery outlined the potential role of MnSOD mimetics as topical agents enhancing wound healing.
Collapse
Affiliation(s)
- Gregory Lucien Bellot
- Department of Hand & Reconstructive Microsurgery, University Orthopedic, Hand & Reconstructive Microsurgery Cluster, National University Health System, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Xiaoke Dong
- Department of Hand & Reconstructive Microsurgery, University Orthopedic, Hand & Reconstructive Microsurgery Cluster, National University Health System, Singapore
| | - Amitabha Lahiri
- Department of Hand & Reconstructive Microsurgery, University Orthopedic, Hand & Reconstructive Microsurgery Cluster, National University Health System, Singapore
| | - Sandeep Jacob Sebastin
- Department of Hand & Reconstructive Microsurgery, University Orthopedic, Hand & Reconstructive Microsurgery Cluster, National University Health System, Singapore
| | - Ines Batinic-Haberle
- Department of Radiation Oncology, Duke University School of Medicine, Durham, NC, USA
| | - Shazib Pervaiz
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Medical Science Cluster Cancer Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; National University Cancer Institute, National University Health System, Singapore, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore; School of Pharmacy and Biomedical Sciences, Curtin University, Perth, Australia.
| | - Mark Edward Puhaindran
- Department of Hand & Reconstructive Microsurgery, University Orthopedic, Hand & Reconstructive Microsurgery Cluster, National University Health System, Singapore.
| |
Collapse
|
|
28
|
Effect of negative pressure wound therapy on molecular markers in diabetic foot ulcers. Gene 2018; 667:56-61. [PMID: 29758297 DOI: 10.1016/j.gene.2018.05.032] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 05/07/2018] [Accepted: 05/10/2018] [Indexed: 11/22/2022]
Abstract
Diabetic foot ulcers are one of the most common complications of diabetes with high morbidity and mortality. Negative pressure wound therapy (NPWT) is one of the treatment modalities that facilitates the wound healing process; however, its molecular mechanism remains unclear. The aim of this study was to investigate the mechanism of action of NPWT in the treatment of diabetic foot ulcers via measuring the tissue expression of genes related to the wound healing process. The study included 40 patients with diabetic foot ulceration, 20 of them received NPWT and the other 20 were a control group treated with advanced moist therapy. Granulation tissue biopsies were obtained before and 10 days after treatment in both groups and subjected to real-time polymerase chain reaction to measure the mRNA expression of TGF-β1, VEGF, TNF-α, IL-1β, MMP-1, MMP-9 and TIMP-1 which are involved in the wound healing pathway. After 10 days of treatment with NPWT, the mRNA levels of IL-1β, TNF-α, MMP-1, and MMP-9 were significantly downregulated, while the levels of VEGF, TGF-β1 and TIMP-1 were significantly increased. Our study demonstrated that NPWT promotes wound healing in diabetic foot ulcers possibly by affecting growth factors, inflammatory cytokines, and matrix metalloproteinases.
Collapse
|
|
29
|
Moore AL, Marshall CD, Barnes LA, Murphy MP, Ransom RC, Longaker MT. Scarless wound healing: Transitioning from fetal research to regenerative healing. WILEY INTERDISCIPLINARY REVIEWS. DEVELOPMENTAL BIOLOGY 2018; 7:10.1002/wdev.309. [PMID: 29316315 PMCID: PMC6485243 DOI: 10.1002/wdev.309] [Citation(s) in RCA: 90] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/25/2016] [Revised: 09/07/2017] [Accepted: 10/27/2017] [Indexed: 01/08/2023]
Abstract
Since the discovery of scarless fetal skin wound healing, research in the field has expanded significantly with the hopes of advancing the finding to adult human patients. There are several differences between fetal and adult skin that have been exploited to facilitate scarless healing in adults including growth factors, cytokines, and extracellular matrix substitutes. However, no one therapy, pathway, or cell subtype is sufficient to support scarless wound healing in adult skin. More recently, products that contain or mimic fetal and adult uninjured dermis were introduced to the wound healing market with promising clinical outcomes. Through our review of the major experimental targets of fetal wound healing, we hope to encourage research in areas that may have a significant clinical impact. Additionally, we will investigate therapies currently in clinical use and evaluate whether they represent a legitimate advance in regenerative medicine or a vulnerary agent. WIREs Dev Biol 2018, 7:e309. doi: 10.1002/wdev.309 This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration Plant Development > Cell Growth and Differentiation Adult Stem Cells, Tissue Renewal, and Regeneration > Environmental Control of Stem Cells.
Collapse
Affiliation(s)
- Alessandra L. Moore
- Department of Surgery, Brigham and Women’s Hospital, Boston, Massachusetts
- Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Clement D. Marshall
- Department of Surgery, Brigham and Women’s Hospital, Boston, Massachusetts
- Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Leandra A. Barnes
- Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Matthew P. Murphy
- Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Ryan C. Ransom
- Department of Surgery, Stanford University School of Medicine, Stanford, California
- Institute of Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California
| | - Michael T. Longaker
- Department of Surgery, Stanford University School of Medicine, Stanford, California
- Institute of Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California
| |
Collapse
|
|
30
|
Barnes LA, Marshall CD, Leavitt T, Hu MS, Moore AL, Gonzalez JG, Longaker MT, Gurtner GC. Mechanical Forces in Cutaneous Wound Healing: Emerging Therapies to Minimize Scar Formation. Adv Wound Care (New Rochelle) 2018; 7:47-56. [PMID: 29392093 PMCID: PMC5792236 DOI: 10.1089/wound.2016.0709] [Citation(s) in RCA: 127] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2016] [Accepted: 12/15/2016] [Indexed: 12/25/2022] Open
Abstract
Significance: Excessive scarring is major clinical and financial burden in the United States. Improved therapies are necessary to reduce scarring, especially in patients affected by hypertrophic and keloid scars. Recent Advances: Advances in our understanding of mechanical forces in the wound environment enable us to target mechanical forces to minimize scar formation. Fetal wounds experience much lower resting stress when compared with adult wounds, and they heal without scars. Therapies that modulate mechanical forces in the wound environment are able to reduce scar size. Critical Issues: Increased mechanical stresses in the wound environment induce hypertrophic scarring via activation of mechanotransduction pathways. Mechanical stimulation modulates integrin, Wingless-type, protein kinase B, and focal adhesion kinase, resulting in cell proliferation and, ultimately, fibrosis. Therefore, the development of therapies that reduce mechanical forces in the wound environment would decrease the risk of developing excessive scars. Future Directions: The development of novel mechanotherapies is necessary to minimize scar formation and advance adult wound healing toward the scarless ideal. Mechanotransduction pathways are potential targets to reduce excessive scar formation, and thus, continued studies on therapies that utilize mechanical offloading and mechanomodulation are needed.
Collapse
Affiliation(s)
- Leandra A. Barnes
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Clement D. Marshall
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Tripp Leavitt
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Michael S. Hu
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California
- Department of Surgery, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii
| | | | - Jennifer G. Gonzalez
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Michael T. Longaker
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Geoffrey C. Gurtner
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California
| |
Collapse
|
|
31
|
Yang SL, Zhu LY, Han R, Sun LL, Dou JT. Effect of Negative Pressure Wound Therapy on Cellular Fibronectin and Transforming Growth Factor-β1 Expression in Diabetic Foot Wounds. Foot Ankle Int 2017; 38:893-900. [PMID: 28459181 DOI: 10.1177/1071100717704940] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Chronic diabetic foot wounds are a leading cause of amputation, morbidity, and hospitalization for patients with diabetes. Negative-pressure wound therapy (NPWT) can putatively facilitate wound healing, but the underlying mechanisms remain unclear. Cellular fibronectin (cFN) and transforming growth factor-β1 (TGF-β1) play an important role in wound healing. This prospective randomized controlled trial evaluated the effects of NPWT on the production of cFN and the expression of TGF-β1 in diabetic foot wounds of patients. METHODS From January 2012 to January 2015, 40 patients with diabetic foot wounds were randomly and equally apportioned to receive either NPWT or advanced moist wound therapy (control) for 7 days. Granulation tissue was harvested before and after treatment. Immunohistochemistry and Western blot were performed to evaluate protein levels of cFN and TGF-β1, and real-time polymerase chain reaction (PCR) to measure corresponding mRNA expressions. RESULTS NPWT facilitated the expression of cFN and TGF-β1 in diabetic foot wounds. Immunohistochemical analysis revealed higher levels of cFN and TGF-β1 in the NPWT group than in the control group. Western blot and real-time PCR analysis further showed that protein and mRNA levels of cFN or TGF-β1 were higher in the NPWT group than that in the control group ( P < .01, both). CONCLUSION Our results showed that NPWT facilitated the production of cFN and the expression of TGF-β1 in granulation tissue in diabetic foot ulcers. LEVEL OF EVIDENCE Level I, randomized controlled study.
Collapse
Affiliation(s)
- Shao Ling Yang
- 1 Department of Endocrinology, Chinese PLA General Hospital (301 Hospital), Beijing, China.,2 Department of Endocrinology, Bethune International Peace Hospital of PLA, Shijiazhuang, China
| | - Lv Yun Zhu
- 2 Department of Endocrinology, Bethune International Peace Hospital of PLA, Shijiazhuang, China
| | - Rui Han
- 3 Department of Neurology, First Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Lei Lei Sun
- 4 Department of Endocrinology, Armed Police Hospital of Shandong, Shandong, China
| | - Jing Tao Dou
- 1 Department of Endocrinology, Chinese PLA General Hospital (301 Hospital), Beijing, China
| |
Collapse
|
|
32
|
Liu J, Hu F, Tang J, Tang S, Xia K, Wu S, Yin C, Wang S, He Q, Xie H, Zhou J. Homemade-device-induced negative pressure promotes wound healing more efficiently than VSD-induced positive pressure by regulating inflammation, proliferation and remodeling. Int J Mol Med 2017; 39:879-888. [PMID: 28290607 PMCID: PMC5360422 DOI: 10.3892/ijmm.2017.2919] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Accepted: 02/22/2017] [Indexed: 02/05/2023] Open
Abstract
Vacuum sealing drainage (VSD) is an effective technique used to promote wound healing. However, recent studies have shown that it exerts positive pressure (PP) rather than negative pressure (NP) on skin. In this study, we created a homemade device that could maintain NP on the wound, and compared the therapeutic effects of VSD-induced PP to those of our homemade device which induced NP on wound healing. The NP induced by our device required less time for wound healing and decreased the wound area more efficiently than the PP induced by VSD. NP and PP both promoted the inflammatory response by upregulating neutrophil infiltration and interleukin (IL)‑1β expression, and downregulating IL‑10 expression. Higher levels of epidermal growth factor (EGF), transforming growth factor (TGF)‑β and platelet-derived growth factor (PDGF), and lower levels of basic fibroblast growth factor (bFGF) were observed in the wound tissue treated with NP compared to the wound tissue exposed to PP. Proliferation in the wound tissue exposed to NP on day 10 was significantly higher than that in wound tissue exposed to PP. NP generated more fibroblasts, keratinized stratified epithelium, and less epithelia with stemness than PP. The levels of ccollagen Ⅰ and Ⅲ were both decreased in both the NP and PP groups. NP induced a statistically significant increase in the expression of fibronectin (FN) on days 3 and 10 compared to PP. Furthermore, the level of matrix metalloproteinase (MMP)‑13 increased in the NP group, but decreased in the PP group on day 3. NP also induced a decrease in the levels of tissue inhibitor of metalloproteinase (TIMP)‑1 and TIMP‑2 during the early stages of wound healing, which was significantly different from the increasing effect of PP on TIMP‑1 and TIMP‑2 levels at the corresponding time points. On the whole, our data indicate that our homemade device which induced NP, was more efficient than VSD‑induced PP on wound healing by regulating inflammation, secretion, proliferation and the distribution of different cells in wound tissue.
Collapse
Affiliation(s)
- Jinyan Liu
- Department of Nuclear Medicine, The First Xiangya Hospital of Central South University, Changsha, Hunan 410008
| | - Feng Hu
- Department of Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013
| | - Jintian Tang
- Institute of Medical Physics and Engineering, Tsinghua University, Beijing 100084
| | - Shijie Tang
- Cleft Lip and Palate Treatment Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041
| | - Kun Xia
- Key Laboratory of Medical Information Research, Central South University, Changsha, Hunan
| | | | - Chaoqi Yin
- Department of Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013
| | - Shaohua Wang
- Department of Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013
| | - Quanyong He
- Department of Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013
| | - Huiqing Xie
- Rehabilitation Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
| | - Jianda Zhou
- Department of Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013
- Correspondence to: Professor Jianda Zhou, Department of Plastic Surgery, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, Hunan 410013, P.R. China, E-mail:
| |
Collapse
|
|
33
|
Panayi AC, Leavitt T, Orgill DP. Evidence based review of negative pressure wound therapy. World J Dermatol 2017; 6:1-16. [DOI: 10.5314/wjd.v6.i1.1] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Revised: 10/15/2016] [Accepted: 01/14/2017] [Indexed: 02/06/2023] Open
Abstract
Vacuum-assisted closure, sometimes referred to as microdeformational wound therapy or most commonly negative pressure wound therapy (NPWT), has significantly improved wound care over the past two decades. NPWT is known to affect wound healing through four primary mechanisms (macrodeformation, microdeformation, fluid removal, and alteration of the wound environment) and various secondary mechanisms (including neurogenesis, angiogenesis, modulation of inflammation, and alterations in bioburden) which are described in this review. In addition, the technique has many established uses, for example in wound healing of diabetic and pressure ulcers, as well as burn and blast wounds. This therapy also has many uses whose efficacy has yet to be confirmed, for example the use in digestive surgery. Modifications of the traditional NPWT have also been established and are described in detail. This therapy has various considerations and contraindications which are summarized in this review. Finally, future perspectives, such as the optimal cycling of the treatment and the most appropriate interface material, are touched upon in the final segment. Overall, despite the fact that questions remain to be answered about NPWT, this technology is a major breakthrough in wound healing with significant potential use both in the hospital but also in the community.
Collapse
|
|
34
|
Abstract
Wound healing is a highly complex chain of events, and although it may never be possible to eliminate the risk of experiencing a wound, clinicians' armamentarium continues to expand with methods to manage it. The phases of wound healing are the inflammatory phase, the proliferative phase, and the maturation phase. The pathway of healing is determined by characteristics of the wound on initial presentation, and it is vital to select the appropriate method to treat the wound based on its ability to avoid hypoxia, infection, excessive edema, and foreign bodies.
Collapse
|
|
35
|
Complementary Effects of Negative-Pressure Wound Therapy and Pulsed Radiofrequency Energy on Cutaneous Wound Healing in Diabetic Mice. Plast Reconstr Surg 2017; 139:105-117. [DOI: 10.1097/prs.0000000000002909] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
|
|
36
|
Nie B, Yue B. Biological effects and clinical application of negative pressure wound therapy: a review. J Wound Care 2016; 25:617-626. [DOI: 10.12968/jowc.2016.25.11.617] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Affiliation(s)
- B. Nie
- Associated Professor Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - B. Yue
- Associated Professor Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| |
Collapse
|
|
37
|
Lalezari S, Lee CJ, Borovikova AA, Banyard DA, Paydar KZ, Wirth GA, Widgerow AD. Deconstructing negative pressure wound therapy. Int Wound J 2016; 14:649-657. [PMID: 27681204 DOI: 10.1111/iwj.12658] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2016] [Revised: 07/06/2016] [Accepted: 07/10/2016] [Indexed: 12/13/2022] Open
Abstract
Since its introduction 20 years ago for the treatment of chronic wounds, negative pressure wound therapy use has expanded to a variety of other wound types. Various mechanisms of action for its efficacy in wound healing have been postulated, but no unifying theory exists. Proposed mechanisms include induction of perfusion changes, microdeformation, macrodeformation, exudate control and decreasing the bacterial load in the wound. We surmise that these different mechanisms have varying levels of dominance in each wound type. Specifically, negative pressure wound therapy is beneficial to acute open wounds because it induces perfusion changes and formation of granulation tissue. Post-surgical incisional wounds are positively affected by perfusion changes and exudate control. In the context of chronic wounds, negative pressure wound therapy removes harmful and corrosive substances within the wounds to affect healing. When skin grafts and dermal substitutes are used to close a wound, negative pressure wound therapy is effective in promoting granulation tissue formation, controlling exudate and decreasing the bacterial load in the wound. In this review, we elucidate some of the mechanisms behind the positive wound healing effects of negative pressure wound therapy, providing possible explanations for these effects in different wound types.
Collapse
Affiliation(s)
- Shadi Lalezari
- Center for Tissue Engineering, Department of Plastic Surgery, University of California, Irvine, CA, USA
| | - Christine J Lee
- Center for Tissue Engineering, Department of Plastic Surgery, University of California, Irvine, CA, USA
| | - Anna A Borovikova
- Center for Tissue Engineering, Department of Plastic Surgery, University of California, Irvine, CA, USA
| | - Derek A Banyard
- Center for Tissue Engineering, Department of Plastic Surgery, University of California, Irvine, CA, USA
| | - Keyianoosh Z Paydar
- Center for Tissue Engineering, Department of Plastic Surgery, University of California, Irvine, CA, USA
| | - Garrett A Wirth
- Center for Tissue Engineering, Department of Plastic Surgery, University of California, Irvine, CA, USA
| | - Alan D Widgerow
- Center for Tissue Engineering, Department of Plastic Surgery, University of California, Irvine, CA, USA
| |
Collapse
|
|
38
|
Skrinjar E, Duschek N, Bayer GS, Assadian O, Koulas S, Hirsch K, Basic J, Assadian A. Randomized controlled trial comparing the combination of a polymeric membrane dressing plus negative pressure wound therapy against negative pressure wound therapy alone: The WICVAC study. Wound Repair Regen 2016; 24:928-935. [PMID: 27313054 DOI: 10.1111/wrr.12457] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2015] [Accepted: 06/12/2016] [Indexed: 02/04/2023]
Abstract
Negative pressure wound therapy (NPWT) is the treatment of choice for chronic wounds; yet, it is associated with considerable workload. Prompted by its nonadhesive and wound-healing properties, this study investigated the effect of an additional polymeric membrane interface dressing (PMD; PolyMem WIC) in NPWT. From October 2011 to April 2013, 60 consecutive patients with chronic leg wounds or surgical site infections after revascularization of lower extremities were randomly allocated to either treatment with conventional NPWT (control arm) or NPWT with an additional PMD (intervention arm). The primary outcome was wound healing achieved within 30 days, the secondary endpoints included: number of days between dressing changes, wound-related pain, cost efficiency, and occurrence of adverse events (ClinTrials.gov Identifier: NCT02399722). Forty-seven patients completed follow-up. No difference in wound healing was observed (p > 0.05) between both study arms. The additional PMD allowed significantly longer wearing times (days) between dressing changes (intervention: 8.8 ± 0.5, control: 4.8 ± 0.2; p < 0.001). Pain was slightly higher in patients randomized to NPWT alone (VAS score: 4.8 ± 2.9) compared to NPWT + PMD (VAS score: 3.0 ± 2.9, p = 0.063). No wound infections were observed. Costs were reduced by 34% per patient in the intervention arm. These results suggest that the combination of NPWT and an additional interface PMD is a safe and economic method for the treatment of chronic wounds, which requires significantly fewer dressing changes for a comparable wound healing.
Collapse
Affiliation(s)
- Edda Skrinjar
- Department of Vascular and Endovascular Surgery, Wilhelminenhospital, Vienna, Austria.
| | - Nikolaus Duschek
- Department of Dermatology and Venerology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Vaud, Switzerland
| | - Gottfried S Bayer
- Department of Vascular and Endovascular Surgery, Wilhelminenhospital, Vienna, Austria
| | - Ojan Assadian
- Institute for Skin Integrity and Infection Prevention, School of Human & Health Sciences, University of Huddersfield, Huddersfield, United Kingdom
| | - Spyridon Koulas
- Department of Vascular and Endovascular Surgery, Wilhelminenhospital, Vienna, Austria
| | - Kornelia Hirsch
- Department of Vascular and Endovascular Surgery, Wilhelminenhospital, Vienna, Austria
| | - Jelena Basic
- Department of Vascular and Endovascular Surgery, Wilhelminenhospital, Vienna, Austria
| | - Afshin Assadian
- Department of Vascular and Endovascular Surgery, Wilhelminenhospital, Vienna, Austria
| |
Collapse
|
|
39
|
Mechanotransduction: Relevance to Physical Therapist Practice-Understanding Our Ability to Affect Genetic Expression Through Mechanical Forces. Phys Ther 2016; 96:712-21. [PMID: 26700270 DOI: 10.2522/ptj.20150073] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2015] [Accepted: 12/13/2015] [Indexed: 12/20/2022]
Abstract
Mechanotransduction, the mechanism by which mechanical perturbation influences genetic expression and cellular behavior, is an area of molecular biology undergoing rapid exploration and discovery. Cells are sensitive to forces such as shear, tension, and compression, and they respond accordingly through cellular proliferation, migration, tissue repair, altered metabolism, and even stem cell differentiation and maturation. The study of how cells sense and respond to mechanical stimulation is under robust expansion, with new scientific methods and technologies at our disposal. The application of these technologies to physical therapist practice may hold answers to some of our age-old questions while creating new avenues for our profession to optimize movement for societal health. Embracing this science as foundational to our profession will allow us to be valuable scientific collaborators with distinctive knowledge of the effects of loading. These partnerships will be key to augmenting the clinical utility of emerging therapies such as regenerative medicine, tissue engineering, and gene therapy. Collaboration with other scientific disciplines in these endeavors, along with the inclusion and application of these discoveries in our academic programs, will enhance the understanding of the impact of our practice on biologic and genetic processes. A basic understanding of mechanotransduction and its relevance to physical therapist practice is warranted to begin the conversation.
Collapse
|
|
40
|
De Jesus AM, Aghvami M, Sander EA. A Combined In Vitro Imaging and Multi-Scale Modeling System for Studying the Role of Cell Matrix Interactions in Cutaneous Wound Healing. PLoS One 2016; 11:e0148254. [PMID: 26840835 PMCID: PMC4739727 DOI: 10.1371/journal.pone.0148254] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Accepted: 01/15/2016] [Indexed: 12/22/2022] Open
Abstract
Many cell types remodel the extracellular matrix of the tissues they inhabit in response to a wide range of environmental stimuli, including mechanical cues. Such is the case in dermal wound healing, where fibroblast migrate into and remodel the provisional fibrin matrix in a complex manner that depends in part on the local mechanical environment and the evolving multi-scale mechanical interactions of the system. In this study, we report on the development of an image-based multi-scale mechanical model that predicts the short-term (24 hours), structural reorganization of a fibrin gel by fibroblasts. These predictive models are based on an in vitro experimental system where clusters of fibroblasts (i.e., explants) were spatially arranged into a triangular geometry onto the surface of fibrin gels that were subjected to either Fixed or Free in-plane mechanical constraints. Experimentally, regional differences in short-term structural remodeling and cell migration were observed for the two gel boundary conditions. A pilot experiment indicated that these small differences in the short-term remodeling of the fibrin gel translate into substantial differences in long-term (4 weeks) remodeling, particularly in terms of collagen production. The multi-scale models were able to predict some regional differences in remodeling and qualitatively similar reorganization patterns for the two boundary conditions. However, other aspects of the model, such as the magnitudes and rates of deformation of gel, did not match the experiments. These discrepancies between model and experiment provide fertile ground for challenging model assumptions and devising new experiments to enhance our understanding of how this multi-scale system functions. These efforts will ultimately improve the predictions of the remodeling process, particularly as it relates to dermal wound healing and the reduction of patient scarring. Such models could be used to recommend patient-specific mechanical-based treatment dependent on parameters such as wound geometry, location, age, and health.
Collapse
Affiliation(s)
- Aribet M. De Jesus
- Department of Biomedical Engineering, University of Iowa, Iowa City, IA, United States of America
| | - Maziar Aghvami
- Department of Biomedical Engineering, University of Iowa, Iowa City, IA, United States of America
| | - Edward A. Sander
- Department of Biomedical Engineering, University of Iowa, Iowa City, IA, United States of America
- * E-mail:
| |
Collapse
|
|
41
|
Siqueira MBP, Ramanathan D, Klika AK, Higuera CA, Barsoum WK. Role of negative pressure wound therapy in total hip and knee arthroplasty. World J Orthop 2016; 7:30-37. [PMID: 26807353 PMCID: PMC4716568 DOI: 10.5312/wjo.v7.i1.30] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2015] [Revised: 09/15/2015] [Accepted: 11/25/2015] [Indexed: 02/06/2023] Open
Abstract
Negative-pressure wound therapy (NPWT) has been a successful modality of wound management which is in widespread use in several surgical fields. The main mechanisms of action thought to play a role in enhancing wound healing and preventing surgical site infection are macrodeformation and microdeformation of the wound bed, fluid removal, and stabilization of the wound environment. Due to the devastating consequences of infection in the setting of joint arthroplasty, there has been some interest in the use of NPWT following total hip arthroplasty and total knee arthroplasty. However, there is still a scarcity of data reporting on the use of NPWT within this field and most studies are limited by small sample sizes, high variability of clinical settings and end-points. There is little evidence to support the use of NPWT as an adjunctive treatment for surgical wound drainage, and for this reason surgical intervention should not be delayed when indicated. The prophylactic use of NPWT after arthroplasty in patients that are at high risk for postoperative wound drainage appears to have the strongest clinical evidence. Several clinical trials including single-use NPWT devices for this purpose are currently in progress and this may soon be incorporated in clinical guidelines as a mean to prevent periprosthetic joint infections.
Collapse
|
|
42
|
Ogawa R. Mechanobiology and Mechanotherapy in Tissue Engineering. IN SITU TISSUE REGENERATION 2016:165-181. [DOI: 10.1016/b978-0-12-802225-2.00009-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
|
43
|
Rhee SM, Valle MF, Wilson LM, Lazarus G, Zenilman JM, Robinson KA. Negative pressure wound therapy technologies for chronic wound care in the home setting: A systematic review. Wound Repair Regen 2015; 23:506-17. [PMID: 25845268 DOI: 10.1111/wrr.12295] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2014] [Revised: 03/31/2015] [Indexed: 12/19/2022]
Abstract
The use of negative pressure wound therapy (NPWT) is increasing in both the inpatient and outpatient settings. We conducted a systematic review on the efficacy and safety of NPWT for the treatment of chronic wounds in the home setting. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature, up to June 2014. Two independent reviewers screened search results. Seven studies met our criteria for inclusion. Six of the studies compared NPWT devices to other wound care methods and one study compared two different NPWT technologies. Data were limited by variability in the types of comparator groups, methodological limitations, and poor reporting of outcomes. We were unable to draw conclusions about the efficacy or safety of NPWT for the treatment of chronic wounds in the home setting due to the insufficient evidence. Consensus is needed on the methods of conducting and reporting wound care research so that future studies are able inform decisions about the use of NPWT in the home environment for chronic wounds.
Collapse
Affiliation(s)
- Susan M Rhee
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center
| | - M Frances Valle
- Department of Organizational Systems and Adult Health, School of Nursing, University of Maryland
| | - Lisa M Wilson
- Department of Health Policy and Management, Johns Hopkins University Bloomberg School of Public Health
| | - Gerald Lazarus
- Department of Dermatology, Johns Hopkins University School of Medicine
| | - Jonathan M Zenilman
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center
| | - Karen A Robinson
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| |
Collapse
|
|
44
|
Yang SL, Han R, Liu Y, Hu LY, Li XL, Zhu LY. Negative pressure wound therapy is associated with up-regulation of bFGF and ERK1/2 in human diabetic foot wounds. Wound Repair Regen 2015; 22:548-54. [PMID: 24809625 DOI: 10.1111/wrr.12195] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2013] [Accepted: 04/10/2014] [Indexed: 12/26/2022]
Abstract
Chronic foot wounds are a leading cause of morbidity and hospitalization for patients with diabetes. Negative pressure wound therapy (NPWT) is known to promote healing of diabetic foot wounds, but the underlying molecular mechanisms remain elusive. We propose to gain molecular insights into the wound healing promoting signals underlying the effects of NPWT on diabetic foot wounds in humans. We assessed 30 patients with diabetic foot ulcers. Of these cases, 15 were treated with NPWT, while 15 patients were treated with traditional gauze therapy. Granulated tissue was harvested before and after treatment in both patient groups and histologically analyzed with hematoxylin & eosin as well as Masson's trichrome staining methods. Immunohistochemistry and Western blot analysis was performed to evaluate expression of basic fibroblast growth factor (bFGF) and extracellular signal-regulated kinase (ERK)1/2, previously associated with promoting cellular growth and/or wound healing. Unlike controls, the wounds in the NPWT-treated diabetic patients developed characteristic features of granulated tissue with increased collagen deposition. Immunohistochemical analysis also revealed an increase in bFGF levels in NPWT-treated patients. Western blot analysis further showed a significant up-regulation of bFGF and phosphorylated ERK1/2 protein levels in the NPWT-treated diabetic patients vs. controls. Our studies reveal that NPWT is associated with an up-regulation of bFGF and ERK1/2 signaling, which may be involved in promoting the NPWT-mediated wound healing response.
Collapse
Affiliation(s)
- Shao-Ling Yang
- Department of Endocrinology, Peace Hospital of PLA, Shijiazhuang, Hebei, China
| | | | | | | | | | | |
Collapse
|
|
45
|
Montani C, Steimberg N, Boniotti J, Biasiotto G, Zanella I, Diafera G, Biunno I, Caimi L, Mazzoleni G, Di Lorenzo D. Fibroblasts maintained in 3 dimensions show a better differentiation state and higher sensitivity to estrogens. Toxicol Appl Pharmacol 2014; 280:421-33. [DOI: 10.1016/j.taap.2014.08.021] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Revised: 07/24/2014] [Accepted: 08/12/2014] [Indexed: 01/07/2023]
|
|
46
|
Glass GE, Murphy GF, Esmaeili A, Lai LM, Nanchahal J. Systematic review of molecular mechanism of action of negative-pressure wound therapy. Br J Surg 2014; 101:1627-36. [PMID: 25294112 DOI: 10.1002/bjs.9636] [Citation(s) in RCA: 139] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Revised: 05/19/2014] [Accepted: 07/25/2014] [Indexed: 01/17/2023]
Abstract
BACKGROUND Negative-pressure wound therapy (NPWT) promotes angiogenesis and granulation, in part by strain-induced production of growth factors and cytokines. As their expression profiles are being unravelled, it is pertinent to consider the mode of action of NPWT at the molecular level. METHODS MEDLINE (January 1997 to present), Embase (January 1997 to present), PubMed (no time limit), the Cochrane Database of Systematic Reviews and the Cochrane Controlled Trials Register were searched for articles that evaluated the influence of NPWT on growth factor expression quantitatively. RESULTS Sixteen studies met the inclusion criteria. Tumour necrosis factor expression was reduced in acute and chronic wounds, whereas expression of interleukin (IL) 1β was reduced in acute wounds only. Systemic IL-10 and local IL-8 expression were increased by NPWT. Expression of vascular endothelial growth factor, fibroblast growth factor 2, transforming growth factor β and platelet-derived growth factor was increased, consistent with mechanoreceptor and chemoreceptor transduction in response to stress and hypoxia. Matrix metalloproteinase-1, -2, -9 and -13 expression was reduced but there was no effect on their enzymatic inhibitor, tissue inhibitor of metalloproteinase 1. CONCLUSION Cytokine and growth factor expression profiles under NPWT suggest that promotion of wound healing occurs by modulation of cytokines to an anti-inflammatory profile, and mechanoreceptor and chemoreceptor-mediated cell signalling, culminating in angiogenesis, extracellular matrix remodelling and deposition of granulation tissue. This provides a molecular basis for understanding NPWT.
Collapse
Affiliation(s)
- G E Glass
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, London, UK; Departments of Plastic Surgery, Royal Free Hospital, London, UK
| | | | | | | | | |
Collapse
|
|
47
|
Lancerotto L, Orgill DP. Mechanoregulation of Angiogenesis in Wound Healing. Adv Wound Care (New Rochelle) 2014; 3:626-634. [PMID: 25302137 DOI: 10.1089/wound.2013.0491] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2013] [Accepted: 11/06/2013] [Indexed: 12/15/2022] Open
Abstract
Significance: Mechanical forces are important regulators of cell and tissue function. Endothelial cells proliferate in response to tissue stretch and the mechanical properties of the environment direct capillary sprouting and growth. As the vascular network is a key factor in physiology and disease, control of the vascularity by means of mechanical forces could lead to the development of innovative therapeutic strategies. Recent Advances: Increased understanding of mechanobiology has stimulated translational research and allowed the development and optimization of clinical devices that exploit mechanical forces for the treatment of diseases, in particular in the field of wound healing. Stretching in distraction osteogenesis and tissue expansion induces neogenesis of well-vascularized tissues. In micro-deformational wound therapy, micro-mechanical distortions of the wound bed stimulate cell proliferation and angiogenesis by stretching resident cells to improve healing of difficult wounds. Relief from tension antagonizes proliferation and angiogenesis in primarily closed wounds allowing for better scar quality. Critical Issues: The integration of mechanobiology into traditional cell biology and pathophysiology in general is not yet complete and further research is needed to fill existing gaps, in particular in the complexity of in vivo conditions. Future Directions: Still largely unexplored approaches based on mechanical perturbation of the micro-/macro-environment can be devised to overcome the limits of current strategies in a broad spectrum of clinical conditions.
Collapse
Affiliation(s)
- Luca Lancerotto
- Clinic of Plastic Surgery, University of Padova , Italy . ; Division of Plastic Surgery, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts
| | - Dennis P Orgill
- Division of Plastic Surgery, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts
| |
Collapse
|
|
48
|
Effects of negative pressure wound therapy on mesenchymal stem cells proliferation and osteogenic differentiation in a fibrin matrix. PLoS One 2014; 9:e107339. [PMID: 25216182 PMCID: PMC4162584 DOI: 10.1371/journal.pone.0107339] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Accepted: 08/10/2014] [Indexed: 12/22/2022] Open
Abstract
Vacuum-assisted closure (VAC) negative pressure wound therapy (NPWT) has been proven to be an effective therapeutic method for the treatment of recalcitrant wounds. However, its role in bone healing remains to be unclear. Here, we investigated the effects of NPWT on rat periosteum-derived mesenchymal stem cells (P-MSCs) proliferation and osteoblastic differentiation in a 3D fibrin matrix. P-MSCs underwent primary culture for three passages before being used to construct cell clots. The fibrin clots were incubated with NPWT under continuous suction at −125 mmHg in a subatmospheric perfusion bioreactor. Clots exposed to atmospheric pressure served as the static control. Compared to the control group, cell proliferation significantly increased in NPWT group after incubation for 3 days. There was no statistical difference in apoptosis rate between two groups. The ALP activity and mineralization of P-MSCs all increased under continuous suction. The expressions of collagen type 1 and transcription factor Cbfa-1 were higher at the 1-, 3-, and 7-day timepoints and the expressions of osteocalcin and integrin β5 were higher at the 3-, and 7-day timepoints in the NPWT group. These results indicate that a short time treatment with NPWT, applied with continuous suction at −125 mmHg, can enhance cellular proliferation of P-MSCs and induce the differentiation toward an osteogenic phenotype. The mechanotransduction molecule integrin β5 was found to be highly expressed after NPWT treatment, which indicates that NPWT may play a positive role in fracture healing through enhance bone formation and decrease bone resorption.
Collapse
|
|
49
|
Huang C, Leavitt T, Bayer LR, Orgill DP. Effect of negative pressure wound therapy on wound healing. Curr Probl Surg 2014; 51:301-31. [PMID: 24935079 DOI: 10.1067/j.cpsurg.2014.04.001] [Citation(s) in RCA: 305] [Impact Index Per Article: 27.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Accepted: 04/15/2014] [Indexed: 12/13/2022]
Abstract
The efficacy of NPWT in promoting wound healing has been largely accepted by clinicians, yet the number of high-level clinical studies demonstrating its effectiveness is small and much more can be learned about the mechanisms of action. In the future, hopefully we will have the data to assist clinicians in selecting optimal parameters for specific wounds including interface material, waveform of suction application, and the amount of suction to be applied. Further investigation into specific interface coatings and instillation therapy are also needed. We believe that advances in mechanobiology, the science of wound healing, the understanding of biofilms, and advances in cell therapy will lead to better care for our patients.
Collapse
|
|
50
|
Wiegand C, White R. Microdeformation in wound healing. Wound Repair Regen 2013; 21:793-9. [DOI: 10.1111/wrr.12111] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2013] [Accepted: 08/12/2013] [Indexed: 02/06/2023]
Affiliation(s)
- Cornelia Wiegand
- Department of Dermatology; University Medical Center Jena; Jena Germany
| | - Richard White
- Institute of Health and Society; University of Worcester; Worcester United Kingdom
| |
Collapse
|