Journal of Clinical Medicine

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18 pages, 9096 KiB

Open AccessArticle

Fragmented Dermo-Epidermal Units (FdeU) as an Emerging Strategy to Improve Wound Healing Process: An In Vitro Evaluation and a Pilot Clinical Study

by Michele Riccio, Elena Bondioli, Letizia Senesi, Nicola Zingaretti, Paolo Gargiulo, Francesco De Francesco, Pier Camillo Parodi and Barbara Zavan

J. Clin. Med. 2023, 12(19), 6165; https://doi.org/10.3390/jcm12196165 - 24 Sep 2023

Cited by 2 | Viewed by 1656

Abstract

Innovative strategies have shown beneficial effects in healing wound management involving, however, a time-consuming and arduous process in clinical contexts. Micro-fragmented skin tissue acts as a slow-released natural scaffold and continuously delivers growth factors, and much other modulatory information, into the microenvironment surrounding [...] Read more.

Innovative strategies have shown beneficial effects in healing wound management involving, however, a time-consuming and arduous process in clinical contexts. Micro-fragmented skin tissue acts as a slow-released natural scaffold and continuously delivers growth factors, and much other modulatory information, into the microenvironment surrounding damaged wounds by a paracrine function on the resident cells which supports the regenerative process. In this study, in vitro and in vivo investigations were conducted to ascertain improved effectiveness and velocity of the wound healing process with the application of fragmented dermo-epidermal units (FdeU), acquired via a novel medical device (Hy-Tissue^® Micrograft Technology). MTT test; LDH test; ELISA for growth factor investigation (IL) IL-2, IL-6, IL-7 IL-8, IL-10; IGF-1; adiponectin; Fibroblast Growth Factor (FGF); Vascular Endothelial Growth Factor (VEGF); and Tumor Necrosis Factor (TNF) were assessed. Therefore, clinical evaluation in 11 patients affected by Chronic Wounds (CW) and treated with FdeU were investigated. Functional outcome was assessed pre-operatory, 2 months after treatment (T0), and 6 months after treatment (T1) using the Wound Bed Score (WBS) and Vancouver Scar Scale (VSS). In this current study, we demonstrate the potential of resident cells to proliferate from the clusters of FdeU seeded in a monolayer that efficiently propagate the chronic wound. Furthermore, in this study we report how the discharge of trophic/reparative proteins are able to mediate the in vitro paracrine function of proliferation, migration, and contraction rate in fibroblasts and keratinocytes. Our investigations recommend FdeU as a favorable tool in wound healing, displaying in vitro growth-promoting potential to enhance current therapeutic mechanisms. Full article

(This article belongs to the Special Issue Wound Healing and Plastic Surgery: Challenges and Innovations)

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17 pages, 3334 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Cold Plasma Therapy in Chronic Wounds—A Multicenter, Randomized Controlled Clinical Trial (Plasma on Chronic Wounds for Epidermal Regeneration Study): Preliminary Results

by Nessr Abu Rached, Susanne Kley, Martin Storck, Thomas Meyer and Markus Stücker

J. Clin. Med. 2023, 12(15), 5121; https://doi.org/10.3390/jcm12155121 - 4 Aug 2023

Cited by 10 | Viewed by 6471

Abstract

Chronic wounds (CWs) pose a significant health challenge in clinical practice. Standard wound therapy (SWT) is currently considered the gold standard. However, recent evidence suggests that cold plasma therapy (CPT) holds promise for improving CWs. In light of this, the POWER study was [...] Read more.

Chronic wounds (CWs) pose a significant health challenge in clinical practice. Standard wound therapy (SWT) is currently considered the gold standard. However, recent evidence suggests that cold plasma therapy (CPT) holds promise for improving CWs. In light of this, the POWER study was conducted as a multicenter, randomized clinical trial to investigate the effect of large-area plasma application compared with SWT in patients with chronic, non-healing arterial or venous wounds on the lower leg. To analyze the interim results, we employed a comprehensive range of statistical tests, including both parametric and non-parametric methods, as well as GLS model regression and an ordinal mixed model. Our findings clearly demonstrate that CPT therapy significantly accelerates wound closure compared with SWT. In fact, complete wound closure was exclusively observed in the CPT group during the intervention period. Additionally, the CPT group required significantly less antibiotic therapy (4%) compared with the SWT group (23%). Furthermore, CPT led to a significant reduction in wound pain and improved quality of life compared with SWT. In conclusion, the study highlights that the combination of CPT and SWT surpasses monotherapy with SWT alone. Full article

(This article belongs to the Special Issue Wound Healing and Plastic Surgery: Challenges and Innovations)

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11 pages, 2123 KiB

Open AccessArticle

Platelets Rich Plasma (PRP) Procedure in the Healing of Atonic Wounds

by Maur Sebastian Horgos, Ovidiu Laurean Pop, Mircea Sandor, Ioan Lucian Borza, Rodica Anamaria Negrean, Adrian Cote, Andreea-Adriana Neamtu, Carmen Grierosu, Liliana Sachelarie and Anca Huniadi

J. Clin. Med. 2023, 12(12), 3890; https://doi.org/10.3390/jcm12123890 - 7 Jun 2023

Cited by 6 | Viewed by 2823

Abstract

(1) Background: Patients suffering from chronic wounds report physical, mental, and social consequences due to their existence and care. There is a global need for tissue repair strategies and, in our case, for chronic wound healing. PRP therapy is based on the fact [...] Read more.

(1) Background: Patients suffering from chronic wounds report physical, mental, and social consequences due to their existence and care. There is a global need for tissue repair strategies and, in our case, for chronic wound healing. PRP therapy is based on the fact that platelet-derived growth factors (PGF) support the three phases of the wound healing and repair cascade (inflammation, proliferation, and remodeling); (2) Methods: A comparative study was carried out on two groups of patients with atonic wounds totaling a total of 80 cases as follows: a study group in which the PRP procedure was applied and a control group in which the biological product was not injected. The study was carried out in the surgery clinic of the Clinical Hospital C.F. Oradea City; (3) Results: A much faster healing was achieved in the case of patients who benefited from the platelet-rich plasma injection therapy compared to the group of patients in whom this therapy was not used. Three weeks after the plasma injection, a considerable reduction of the wound was evident, with some of the patients presenting with a closed wound; (4) Conclusions: The effect of PRP on the healing of chronic wounds is promising in most cases. A positive effect was also highlighted in terms of reducing treatment costs by considerably reducing the materials used as well as the number of hospitalizations for the same pathology. Full article

(This article belongs to the Special Issue Wound Healing and Plastic Surgery: Challenges and Innovations)

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14 pages, 1889 KiB

Open AccessArticle

Construction and Validation of an Image Discrimination Algorithm to Discriminate Necrosis from Wounds in Pressure Ulcers

by Shunsuke Sakakibara, Akira Takekawa, Chikara Takekawa, Satoshi Nagai and Hiroto Terashi

J. Clin. Med. 2023, 12(6), 2194; https://doi.org/10.3390/jcm12062194 - 12 Mar 2023

Cited by 2 | Viewed by 1633

Abstract

Artificial intelligence (AI) in medical care can raise diagnosis accuracy and improve its uniformity. This study developed a diagnostic imaging system for chronic wounds that can be used in medically underpopulated areas. The image identification algorithm searches for patterns and makes decisions based [...] Read more.

Artificial intelligence (AI) in medical care can raise diagnosis accuracy and improve its uniformity. This study developed a diagnostic imaging system for chronic wounds that can be used in medically underpopulated areas. The image identification algorithm searches for patterns and makes decisions based on information obtained from pixels rather than images. Images of 50 patients with pressure sores treated at Kobe University Hospital were examined. The algorithm determined the presence of necrosis with a significant difference (p = 3.39 × 10⁻⁵). A threshold value was created with a luminance difference of 50 for the group with necrosis of 5% or more black pixels. In the no-necrosis group with less than 5% black pixels, the threshold value was created with a brightness difference of 100. The “shallow wounds” were distributed below 100, whereas the “deep wounds” were distributed above 100. When the algorithm was applied to 24 images of 23 new cases, there was 100% agreement between the specialist and the algorithm regarding the presence of necrotic tissue and wound depth evaluation. The algorithm identifies the necrotic tissue and wound depth without requiring a large amount of data, making it suitable for application to future AI diagnosis systems for chronic wounds. Full article

(This article belongs to the Special Issue Wound Healing and Plastic Surgery: Challenges and Innovations)

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11 pages, 2485 KiB

Open AccessArticle

Stromal Vascular Fraction Cells from Individuals Who Have Previously Undergone Radiotherapy Retain Their Pro-Wound Healing Properties

by Lucy V. Trevor, Kirsten Riches-Suman, Ajay L. Mahajan and M. Julie Thornton

J. Clin. Med. 2023, 12(5), 2052; https://doi.org/10.3390/jcm12052052 - 4 Mar 2023

Viewed by 1935

Abstract

Beneficial effects have been observed following the transplant of lipoaspirates containing adipose-derived stem cells into chronic wounds caused by oncologic radiotherapy. It is not yet certain whether adipose-derived stem cells are resistant to radiation exposure. Therefore, the aims of this study were to [...] Read more.

Beneficial effects have been observed following the transplant of lipoaspirates containing adipose-derived stem cells into chronic wounds caused by oncologic radiotherapy. It is not yet certain whether adipose-derived stem cells are resistant to radiation exposure. Therefore, the aims of this study were to isolate stromal vascular fraction from human breast tissue exposed to radiotherapy and determine the presence of adipose-derived stem cells. Stromal vascular fraction from irradiated donor tissue was compared to commercially sourced pre-adipocytes. Immunocytochemistry was used to determine the presence of adipose-derived stem cell markers. Conditioned media from stromal vascular fraction isolated from irradiated donors was used as a treatment in a scratch wound assay of dermal fibroblasts also isolated from irradiated donors and compared to pre-adipocyte conditioned media and serum free control. This is the first report of human stromal vascular fraction being cultured from previously irradiated breast tissue. Stromal vascular fraction conditioned media from irradiated donors had a similar effect in increasing the migration of dermal fibroblasts from irradiated skin to pre-adipocyte conditioned media from healthy donors. Therefore, the ability of adipose-derived stem cells in the stromal vascular fraction to stimulate dermal fibroblasts in wound healing appears to be preserved following radiotherapy. This study demonstrates that stromal vascular fraction from irradiated patients is viable, functional and may have potential for regenerative medicine techniques following radiotherapy. Full article

(This article belongs to the Special Issue Wound Healing and Plastic Surgery: Challenges and Innovations)

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12 pages, 2367 KiB

Open AccessArticle

Negative Pressure Wound Therapy with Instillation: Analysis of the Rinsing Fluid as a Monitoring Tool and Approach to the Inflammatory Process: A Pilot Study

by Niklas Biermann, Stefan Wallner, Teresa Martini, Steffen Spoerl, Lukas Prantl and Christian D. Taeger

J. Clin. Med. 2023, 12(2), 711; https://doi.org/10.3390/jcm12020711 - 16 Jan 2023

Cited by 2 | Viewed by 1953

Abstract

Background: Negative pressure wound therapy with instillation (NPWTi) is an established wound conditioning tool. Previous investigations discovered that the rinsing fluid is a suitable monitoring tool containing various cells and cytokines. Methods: The aim of this pilot study was to analyze rinsing fluid [...] Read more.

Background: Negative pressure wound therapy with instillation (NPWTi) is an established wound conditioning tool. Previous investigations discovered that the rinsing fluid is a suitable monitoring tool containing various cells and cytokines. Methods: The aim of this pilot study was to analyze rinsing fluid samples from patients treated with NPWTi and link them to the clinical course, including microbiological contamination. In 31 consecutive patients with acute and chronic wounds, laboratory analysis was performed to evaluate IL-6, IL-8, bFGF, Tnf-a, and VEGF. Results: IL-6 showed a significant increase to 1540 pg/mL on day two and 860 pg/mL on day four (p = 0.01 and p = 0.04, resp.). IL-8 steadily increased from a median of 2370 pg/mL to a maximum of 19,400 pg/mL on day three (p = 0.01). The median bFGF showed a steady decline from 22 pg/mL to 10 pg/m (p = 0.35) on day three. The median Tnf-a increased from 11 pg/mL to 44 pg/mL (p = 001). The median VEGF values fluctuated but showed an overall increase from 35 pg/mL to 250 pg/mL (p = 0.07). Regarding IL-8, diabetic and non-diabetic patients both showed a gradual increase with non-significant higher median values for the diabetics. The subgroup analysis of IL-6 showed increasing and higher values in cases with bacterial superinfections (p = 0.07). Conclusion: We were able to use an established wound conditioning tool to gather important information about the inflammatory response during NPWTi treatment. Cytokine and cell courses were mostly consistent with the literature, especially in diabetic patients, and should be further investigated. Full article

(This article belongs to the Special Issue Wound Healing and Plastic Surgery: Challenges and Innovations)

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11 pages, 2576 KiB

Open AccessArticle

Evaluation of the Influence of Short Tourniquet Ischemia on Tissue Oxygen Saturation and Skin Temperature Using Two Portable Imaging Modalities

by Wibke Müller-Seubert, Helen Herold, Stephanie Graf, Ingo Ludolph and Raymund E. Horch

J. Clin. Med. 2022, 11(17), 5240; https://doi.org/10.3390/jcm11175240 - 5 Sep 2022

Cited by 5 | Viewed by 1681

Abstract

Background: The exact influence of tourniquet ischemia on a treated extremity remains unclear. Methods: Twenty patients received an operation on one hand under tourniquet ischemia. Twenty healthy volunteers received 10 min of tourniquet ischemia on one of their arms. Measurements of tissue oxygen [...] Read more.

Background: The exact influence of tourniquet ischemia on a treated extremity remains unclear. Methods: Twenty patients received an operation on one hand under tourniquet ischemia. Twenty healthy volunteers received 10 min of tourniquet ischemia on one of their arms. Measurements of tissue oxygen saturation using near-infrared reflectance-based imaging and skin temperature of the dorsum of the hand were performed at five different timepoints (t0 was performed just before the application of the tourniquet ischemia, t1 directly after the application of the tourniquet ischemia, t2 before the release of the ischemia, t3 directly after the release of the ischemia, and t4 on the following day). Results: In both groups, tissue oxygen saturation dropped after the application of the tourniquet ischemia compared to t0 and increased after the release of the tourniquet ischemia. In the patient group, tissue oxygen saturation at t4 was higher compared to t0; in contrast, the level of tissue oxygen saturation in the participant group dropped slightly at t4 compared to t0. The measured skin temperature in the patient group showed an increase during the observation period, while it continuously decreased in the group of healthy participants. Conclusions: Short-term ischemia did not appear to permanently restrict perfusion in this study design. The non-invasive imaging modalities used were easy to handle and allowed repetitive measurement. Full article

(This article belongs to the Special Issue Wound Healing and Plastic Surgery: Challenges and Innovations)

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13 pages, 3877 KiB

Open AccessArticle

Effects of Different Pressure Levels in Topical Negative Pressure Application—Analysis of Perfusion Parameters in a Clinical Skin Model Using Multimodal Imaging Techniques

by Emine Ceylan Aslan-Horch, Raymund E. Horch, Andreas Arkudas, Wibke Müller-Seubert and Ingo Ludolph

J. Clin. Med. 2022, 11(17), 5133; https://doi.org/10.3390/jcm11175133 - 31 Aug 2022

Cited by 6 | Viewed by 2161

Abstract

The effects of topical negative pressure therapy (TNP) have been a subject of research for many years. In this study, we investigated new imaging devices to detect clinical changes that TNP causes on healthy tissue and identified differences in microcirculation created by different [...] Read more.

The effects of topical negative pressure therapy (TNP) have been a subject of research for many years. In this study, we investigated new imaging devices to detect clinical changes that TNP causes on healthy tissue and identified differences in microcirculation created by different pressure levels. We used near-infrared spectroscopy (NIS), thermography, and a vein illuminator to measure the differences in oxygen saturation, tissue temperature, and vein pattern. A control group (−125 mmHg) and three comparison groups with only TNP dressing (Group 1), −25 mmHg (Group 2), and −175 mmHg (Group 3) were established. Thirty minutes of TNP on intact skin was followed by 30 min of resting. A total of 24 participants were measured by all imaging devices at predetermined time points. Oxygen saturation and skin temperature increased by 8.07% and 1.67 °C for the control group, 4.00% and 1.65 °C for Group 2, and 8.45% and 1.68 °C for Group 3. Group 1 showed a slight increase in oxygen saturation and a 2.7 °C increase in skin temperature. Over the 30 min following removal of TNP, oxygen saturation and temperature decreased gradually for all groups. The vein illuminator did not show significant differences in the venous pattern or flow. Our study showed that higher negative pressure values resulted in higher oxygen saturation and higher tissue temperature. Full article

(This article belongs to the Special Issue Wound Healing and Plastic Surgery: Challenges and Innovations)

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10 pages, 1530 KiB

Open AccessArticle

Air-Pressure-Supported Application of Cultured Human Keratinocytes in a Fibrin Sealant Suspension as a Potential Clinical Tool for Large-Scale Wounds

by Celena A. Sörgel, Rafael Schmid, Annika Kengelbach-Weigand, Theresa Promny and Raymund E. Horch

J. Clin. Med. 2022, 11(17), 5032; https://doi.org/10.3390/jcm11175032 - 27 Aug 2022

Cited by 4 | Viewed by 1573

Abstract

The treatment of large-scale skin wounds remains a therapeutic challenge. In most cases there is not enough autologous material available for full coverage. Cultured epithelial autografts are efficient in restoring the lost epidermal cover; however, they have some disadvantages, such as difficult application [...] Read more.

The treatment of large-scale skin wounds remains a therapeutic challenge. In most cases there is not enough autologous material available for full coverage. Cultured epithelial autografts are efficient in restoring the lost epidermal cover; however, they have some disadvantages, such as difficult application and protracted cell cultivation periods. Transplanting a sprayed keratinocyte suspension in fibrin sealant as biological carrier is an option to overcome those disadvantages. Here, we studied different seeding techniques regarding their applicability and advantages on cell survival, attachment, and outgrowth in vitro and thereby improve the cell transfer to the wound bed. Human primary keratinocytes were suspended in a fibrin sealant. WST-8 assay was used to evaluate the vitality for 7 days. Furthermore, the cells were labeled with CellTracker™ CM-Di-I and stained with a life/dead staining. Cell morphology, shape, and distribution were microscopically analyzed. There was a significant increase in vitality while cultivating the cells in fibrin. Sprayed cells were considerably more homogenously distributed. Sprayed cells reached the confluent state earlier than dripped cells. There was no difference in the vitality and morphology in both groups over the observation period. These findings indicate that the sprayed keratinocytes are superior to the application of the cells as droplets. The sprayed application may offer a promising therapeutic option in the treatment of large chronic wounds. Full article

(This article belongs to the Special Issue Wound Healing and Plastic Surgery: Challenges and Innovations)

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12 pages, 2677 KiB

Open AccessArticle

Free Skin Grafting to Reconstruct Donor Sites after Radial Forearm Flap Harvesting: A Prospective Study with Platelet-Rich Fibrin (PRF)

by Anton Straub, Roman Brands, Anna Borgmann, Andreas Vollmer, Julian Hohm, Christian Linz, Urs Müller-Richter, Alexander C. Kübler and Stefan Hartmann

J. Clin. Med. 2022, 11(12), 3506; https://doi.org/10.3390/jcm11123506 - 17 Jun 2022

Cited by 14 | Viewed by 4200

Abstract

Reconstruction of the donor site after radial forearm flap harvesting is a common procedure in maxillofacial plastic surgery. It is normally carried out with split-thickness or full-thickness free skin grafts. Unfortunately, free skin graft transplantation faces wound healing impairments such as necrosis, (partial) [...] Read more.

Reconstruction of the donor site after radial forearm flap harvesting is a common procedure in maxillofacial plastic surgery. It is normally carried out with split-thickness or full-thickness free skin grafts. Unfortunately, free skin graft transplantation faces wound healing impairments such as necrosis, (partial) graft loss, or tendon exposure. Several studies have investigated methods to reduce these impairments and demonstrated improvements if the wound bed is optimised, for example, through negative-pressure wound therapy or vacuum-assisted closure. However, these methods are device-dependent, expansive, and time-consuming. Therefore, the application of platelet-rich fibrin (PRF) to the wound bed could be a simple, cost-effective, and device-independent method to optimise wound-bed conditions instead. In this study, PRF membranes were applied between the wound bed and skin graft. Results of this study indicate improvements in the PRF versus non-PRF group (93.44% versus 86.96% graft survival, p = 0.0292). PRF applied to the wound bed increases graft survival and reduces impairments. A possible explanation for this is the release of growth factors, which stimulate angiogenesis and fibroblast migration. Furthermore, the solid PRF membranes act as a mechanical barrier (“lubrication” layer) to protect the skin graft from tendon motion. The results of this study support the application of PRF in donor-site reconstruction with free skin grafts. Full article

(This article belongs to the Special Issue Wound Healing and Plastic Surgery: Challenges and Innovations)

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15 pages, 1690 KiB

Open AccessSystematic Review

Platelet-Rich Plasma in Chronic Wound Management: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

by Fanni Adél Meznerics, Péter Fehérvári, Fanni Dembrovszky, Kata Dorottya Kovács, Lajos Vince Kemény, Dezső Csupor, Péter Hegyi and András Bánvölgyi

J. Clin. Med. 2022, 11(24), 7532; https://doi.org/10.3390/jcm11247532 - 19 Dec 2022

Cited by 22 | Viewed by 4280

Abstract

Background: Chronic wounds place a heavy burden on the healthcare system due to the prolonged, continuous need for human resources for wound management. Our aim was to investigate the therapeutic effects of platelet-rich plasma on the treatment of chronic wounds. Methods: The systematic [...] Read more.

Background: Chronic wounds place a heavy burden on the healthcare system due to the prolonged, continuous need for human resources for wound management. Our aim was to investigate the therapeutic effects of platelet-rich plasma on the treatment of chronic wounds. Methods: The systematic literature search was performed in four databases. Randomized clinical trials reporting on patients with chronic wounds treated with platelet-rich plasma (PRP) were included, comparing PRP with conventional ulcer therapy. We pooled the data using the random effects model. Our primary outcome was the change in wound size. Results: Our systematic search provided 2688 articles, and we identified 48 eligible studies after the selection and citation search. Thirty-three study groups of 29 RCTs with a total of 2198 wounds showed that the odds for complete closure were significantly higher in the PRP group than in the control group (OR = 5.32; CI: 3.37; 8.40; I² = 58%). Conclusions: PRP is a safe and effective modality to enhance wound healing. By implementing it in clinical practice, platelet-rich plasma could become a widely used, valuable tool as it could not only improve patients’ quality of life but also decrease the healthcare burden of wound management. Full article

(This article belongs to the Special Issue Wound Healing and Plastic Surgery: Challenges and Innovations)

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9 pages, 1488 KiB

Open AccessBrief Report

Device for Negative Pressure Wound Therapy in Low-Resource Regions: Open-Source Description and Bench Test Evaluation

by Ramon Farré, Miguel A. Rodríguez-Lázaro, Julian Gonzalez-Martin, Pedro Castro, Teresa Hospital, Yaroslau Compta, Gorka Solana, David Gozal and Jorge Otero

J. Clin. Med. 2022, 11(18), 5417; https://doi.org/10.3390/jcm11185417 - 15 Sep 2022

Cited by 2 | Viewed by 2484

Abstract

Background: Negative (vacuum) pressure therapy promotes wound healing. However, commercially available devices are unaffordable to most potential users in low- and middle-income countries (LMICs), limiting access to many patients who could benefit from this treatment. This study aimed to design and test a [...] Read more.

Background: Negative (vacuum) pressure therapy promotes wound healing. However, commercially available devices are unaffordable to most potential users in low- and middle-income countries (LMICs), limiting access to many patients who could benefit from this treatment. This study aimed to design and test a cheap and easy-to-build negative pressure device and provide its detailed open-source description, thereby enabling free replication. Methods: the negative pressure device was built using off-the-shelf materials available via e-commerce and was based on a small pump, a pressure transducer, and the simplest Arduino controller with a digital display (total retail cost ≤ 75 US$). The device allows the user to set any therapeutic range of intermittent negative pressure and has two independent safety mechanisms. The performance of the low-cost device was carefully tested on the bench using a phantom wound, producing a realistic exudate flow rate. Results: the device generates the pressure patterns set by the user (25–175 mmHg of vacuum pressure, 0–60 min periods) and can drain exudate flows within the clinical range (up to 1 L/h). Conclusions: a novel, low-cost, easy-to-build negative pressure device for wound healing displays excellent technical performance. The open-source hardware description provided here, which allows for free replication and use in LMICs, will facilitate the application and wider utilization of this therapy to patients. Full article

(This article belongs to the Special Issue Wound Healing and Plastic Surgery: Challenges and Innovations)

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