Browsing by Author "Mathew-Steiner, Shomita S."
Now showing 1 - 10 of 14
Results Per Page
Sort Options
Item A Prospective, Randomized, Controlled Study to Evaluate the Effectiveness of a Fabric-Based Wireless Electroceutical Dressing Compared to Standard-of-Care Treatment Against Acute Trauma and Burn Wound Biofilm Infection(Mary Ann Liebert, 2024) Chan, Rodney K.; Nuutila, Kristo; Mathew-Steiner, Shomita S.; Diaz, Victoria; Anselmo, Kristin; Batchinsky, Maria; Carlsson, Anders; Ghosh, Nandini; Sen, Chandan K.; Roy, Sashwati; Surgery, School of MedicineObjective: Despite advances in the use of topical and parenteral antimicrobial therapy and the practice of early tangential burn wound excision to manage bacterial load, 60% of the mortality from burns is attributed to bacterial biofilm infection. A low electric field (∼1 V) generated by the novel FDA-cleared wireless electroceutical dressing (WED) was previously shown to significantly prevent and disrupt burn biofilm infection in preclinical studies. Based on this observation, the purpose of this clinical trial was to evaluate the efficacy of the WED dressing powered by a silver–zinc electrocouple in the prevention and disruption of biofilm infection. Approach: A prospective, randomized, controlled, single-center clinical trial was performed to evaluate the efficacy of the WED compared with standard-of-care (SoC) dressing to treat biofilms. Burn wounds were randomized to receive either SoC or WED. Biopsies were collected on days 0 and 7 for histology, scanning electron microscopy (SEM) examination of biofilm, and for quantitative bacteriological analyses. Results: In total, 38 subjects were enrolled in the study. In 52% of the WED-treated wounds, little to no biofilm could be detected by SEM. WED significantly lowered or prevented increase of biofilm in all wounds compared with the pair-matched SoC-treated wounds. Innovation: WED is a simple, easy, and rapid method to protect the wound while also inhibiting infection. It is activated by a moist environment and the electrical field induces transient and micromolar amounts of superoxide anion radicals that will prevent bacterial growth. Conclusion: WED decreased biofilm infection better compared with SoC. The study was registered in clinicaltrials.gov as NCT04079998.Item Bacterial Pyocyanin Inducible KRT6A Accelerates Closure of Epithelial Defect Under Conditions of Mitochondrial Dysfunction(Elsevier, 2023) Ghatak, Subhadip; Hemann, Craig; Boslett, James; Singh, Kanhaiya; Sharma, Anu; El Masry, Mohamed S.; Abouhashem, Ahmed Safwat; Ghosh, Nandini; Mathew-Steiner, Shomita S.; Roy, Sashwati; Zweier, Jay L.; Sen, Chandan K.; Surgery, School of MedicineRepair of epithelial defect is complicated by infection and related metabolites. Pyocyanin is one such metabolite which is secreted during Pseudomonas aeruginosa infection. Keratinocyte migration is required for the closure of skin epithelial defects. The current work sought to understand pyocyanin-keratinocyte interaction and its significance in tissue repair. SILAC proteomics identified mitochondrial dysfunction as the top pathway responsive to pyocyanin exposure in human keratinocytes. Consistently, functional studies demonstrated mitochondrial stress, depletion of reducing equivalents, and ATP. Strikingly, despite all the above, pyocyanin markedly accelerated keratinocyte migration. Investigation of underlying mechanisms revealed a new function of KRT6A in keratinocytes. KRT6A was pyocyanin inducible and accelerated closure of epithelial defect. Acceleration of closure was associated with poor quality healing including compromised expression of apical junction proteins. This work recognizes KRT6A for its role of enhancing keratinocyte migration under conditions of threat posed by pyocyanin. Qualitatively deficient junctional proteins under conditions of defensive acceleration of keratinocyte migration explains why an infected wound close with deficient skin barrier function as previously reported.Item Biofilm Management in Wound Care(Wolters Kluwer, 2021) Sen, Chandan K.; Roy, Sashwati; Mathew-Steiner, Shomita S.; Gordillo, Gayle M.; Surgery, School of MedicineLearning objectives: After studying this article, the participant should be able to: 1. Understand the basics of biofilm infection and be able to distinguish between planktonic and biofilm modes of growth. 2. Have a working knowledge of conventional and emerging antibiofilm therapies and their modes of action as they pertain to wound care. 3. Understand the challenges associated with testing and marketing antibiofilm strategies and the context within which these strategies may have effective value. Summary: The Centers for Disease Control and Prevention estimate for human infectious diseases caused by bacteria with a biofilm phenotype is 65 percent and the National Institutes of Health estimate is closer to 80 percent. Biofilms are hostile microbial aggregates because, within their polymeric matrix cocoons, they are protected from antimicrobial therapy and attack from host defenses. Biofilm-infected wounds, even when closed, show functional deficits such as deficient extracellular matrix and impaired barrier function, which are likely to cause wound recidivism. The management of invasive wound infection often includes systemic antimicrobial therapy in combination with débridement of wounds to a healthy tissue bed as determined by the surgeon who has no way of visualizing the biofilm. The exceedingly high incidence of false-negative cultures for bacteria in a biofilm state leads to missed diagnoses of wound infection. The use of topical and parenteral antimicrobial therapy without wound débridement have had limited impact on decreasing biofilm infection, which remains a major problem in wound care. Current claims to manage wound biofilm infection rest on limited early-stage data. In most cases, such data originate from limited experimental systems that lack host immune defense. In making decisions on the choice of commercial products to manage wound biofilm infection, it is important to critically appreciate the mechanism of action and significance of the relevant experimental system. In this work, the authors critically review different categories of antibiofilm products, with emphasis on their strengths and limitations as evident from the published literature.Item Collagen in Wound Healing(MDPI, 2021-05-11) Mathew-Steiner, Shomita S.; Roy, Sashwati; Sen, Chandan K.; Medicine, School of MedicineNormal wound healing progresses through inflammatory, proliferative and remodeling phases in response to tissue injury. Collagen, a key component of the extracellular matrix, plays critical roles in the regulation of the phases of wound healing either in its native, fibrillar conformation or as soluble components in the wound milieu. Impairments in any of these phases stall the wound in a chronic, non-healing state that typically requires some form of intervention to guide the process back to completion. Key factors in the hostile environment of a chronic wound are persistent inflammation, increased destruction of ECM components caused by elevated metalloproteinases and other enzymes and improper activation of soluble mediators of the wound healing process. Collagen, being central in the regulation of several of these processes, has been utilized as an adjunct wound therapy to promote healing. In this work the significance of collagen in different biological processes relevant to wound healing are reviewed and a summary of the current literature on the use of collagen-based products in wound care is provided.Item Deficient functional wound closure as measured by elevated trans-epidermal water loss predicts chronic wound recurrence: An exploratory observational study(Springer Nature, 2024-10-09) Chattopadhyay, Debarati; Sinha, Mithun; Kapoor, Akshay; Kumar, Manoj; Singh, Kanhaiya; Mathew-Steiner, Shomita S.; Sen, Chandan K.; Surgery, School of MedicineA single-center, prospective, observational pilot study was performed to evaluate wound healing endpoint and recurrence by measuring transepidermal water loss (TEWL) post-closure at the site of wound repair. Patients with clinically-defined chronic wounds (such as pressure ulcers, diabetic ulcers, and trauma wounds) who visited the Plastic Surgery outpatient department or were in-patients at the All India Institute of Medical Sciences, Rishikesh, India, and were referred for chronic wound management, were enrolled. Non-invasive point-of-care TEWL measurements were obtained, from closed wound-site and contralateral healthy skin site, starting from confirmation of closure (post-closure, V0) continuing every 2 weeks for a maximum of five visits or until the wound recurred. Statistical analyses of the data involved logistic regression and likelihood ratio chi-square tests to assess differences in TEWL at visit 0 (V0) between the closed wound site and reference skin, with the TEWL score as the sole predictor of recurrence. Of the 72 subjects that completed the study, 44 (61%) showed no recurrence and 28 (39%) had wounds that recurred over a period of 12 weeks. A significant association was found between the V0 (post-closure) TEWL score and the odds of wound recurrence, both in univariate analysis (OR [95%CI] = 1.26[1.14,1.42] (p < 0.001) and after adjusting for covariates in multivariable analysis (OR [95%CI] = 1.34[1.19,1.61] (p < 0.001). The likelihood ratio chi-square analysis demonstrated that the V0 TEWL score is a significant universal predictor of recurrence across all wound types studied. Cases of closed wounds with subsequent recurrence showed an overall higher post-closure V0 TEWL score, compared to those who did not have a wound recurrence, across visits. The TEWL score cut-off value predictive of recurrence was 24.1 g.m-2.h-1 (AUC = 0.967). The outcome of this pilot study on a wide range of chronic wounds leads to the hypothesis that post-closure TEWL at the site of wound healing is a reliable biomarker of wound recurrence. It also raises the question whether the clinical endpoint of wound closure should include re-establishment of skin barrier function as additional criterion. The current standard of care wound closure endpoint calls for re-epithelialization of the wound with no discharge for two consecutive weeks disregarding the functional parameter of restoration of skin barrier function at the wound-site.Item Development and validation of the DHIS2 platform for integrating sociomedical data to study wound care outcomes(Public Library of Science, 2024-12-04) Paddo, Atika Rahman; Kodela, Snigdha; Timsina, Lava; Mathew-Steiner, Shomita S.; Purkayastha, Saptarshi; Sen, Chandan K.; Surgery, School of MedicineWound trajectory and outcomes research has applications in different aspects of wound healing: forecasting wound healing time, access and utilization of wound care services, factors associated with disparities in wound care services, and its quality and outcomes. Wound care research benefits from a well-maintained record management system. In this article, we demonstrate the customization of the District Health Information Software (DHIS2) platform to integrate wound care clinical data with social determinants of health from several Comprehensive Wound Centers (CWC) in Indiana. We describe the modules and features of our platform, such as tracker capture, visualization, and maps. DHIS2 is used in more than 60 countries to monitor and evaluate health programs. However, to the best of our knowledge, this is the first attempt to use DHIS2 as a wound care data warehouse, a platform to perform wound care research for academic researchers and clinical practitioners. Clinicians can use the platform as one of the key tools to make an informed decision in determining the treatment for favorable healing trajectory and wound outcomes. We conducted a usability and acceptance survey among researchers at the Indiana Center for Regenerative Medicine and Engineering and found that DHIS2 can be a suitable infrastructure to manage metadata to import and analyze combined data from disparate sources, including Electronic Medical Records, WoundExpert, and clinical trials management software like REDCap.Item Disposable Patterned Electroceutical Dressing (PED-10) Is Safe for Treatment of Open Clinical Chronic Wounds(Mary Ann Liebert, 2019-04-01) Roy, Sashwati; Prakash, Shaurya; Mathew-Steiner, Shomita S.; Das Ghatak, Piya; Lochab, Varun; Jones, Travis H.; Mohana Sundaram, Prashanth; Gordillo, Gayle M.; Subramaniam, Vish V.; Sen, Chandan K.; Surgery, School of MedicineObjective: To evaluate if patterned electroceutical dressing (PED) is safe for human chronic wounds treatment as reported by wound care providers. Approach: This work reports a pilot feasibility study with the primary objective to determine physically observable effects of PED application on host tissue response from a safety evaluation point of view. For this pilot study, patients receiving a lower extremity amputation with at least one open wound on the part to be amputated were enrolled. Patients were identified through the Ohio State University Wexner Medical Center (OSUWMC) based on inclusion and exclusion criteria through prescreening through the Comprehensive Wound Center's (CWC) Limb Preservation Program and wound physicians and/or providers at OSUWMC. Wounds were treated with the PED before amputation surgery. Results: The intent of the study was to identify if PED was safe for clinical application based on visual observations of adverse or lack of adverse events on skin and wound tissue. The pilot testing performed on a small cohort (N = 8) of patients showed that with engineered voltage regulation of current flow to the open wound, the PED can be used with little to no visually observable adverse effects on chronic human skin wounds. Innovation: The PED was developed as a second-generation tunable electroceutical wound care dressing, which could potentially be used to treat wounds with deeper infections compared with current state of the art that treats wounds with treatment zone limited to the surface near topical application. Conclusion: Technology advances in design and fabrication of electroceutical dressings were leveraged to develop a tunable laboratory prototype that could be used as a disposable low-cost electroceutical wound care dressing on chronic wounds. Design revisions of PED-1 (1 kΩ ballast resistor) circumvented previously observed adverse effects on the skin in the vicinity of an open wound. PED-10 (including a 10 kΩ ballast resistor) was well tolerated in the small cohort of patients (N = 8) on whom it was tested, and the observations reported here warrant a larger study to determine the clinical impact on human wound healing and infection control.Item Electroceutical Management of Bacterial Biofilms and Surgical Infection(Liebert, 2020) Sen, Chandan K.; Mathew-Steiner, Shomita S.; Das, Amitava; Sundaresan, Vishnu Baba; Roy, Sashwati; Surgery, School of MedicineSignificance: In the host–microbe microenvironment, bioelectrical factors influence microbes and hosts as well as host–microbe interactions. This article discusses relevant mechanistic underpinnings of this novel paradigm. It also addresses how such knowledge may be leveraged to develop novel electroceutical solutions to manage biofilm infection. Recent Advances: Systematic review and meta-analysis of several hundred wound studies reported a 78.2% prevalence of biofilms in chronic wounds. Biofilm infection is a major cause of delayed wound healing. In the host–microbe microenvironment, bioelectrical factors influence interactions between microbes and hosts. Critical Issues: Rapid biological responses are driven by electrical signals generated by ion currents moving across cell membranes. Bacterial life, growth, and function rely on a bioelectrical milieu, which when perturbed impairs their ability to form a biofilm, a major threat to health care. Electrokinetic stability of several viral particles depend on electrostatic forces. Weak electrical field strength, otherwise safe for humans, can be anti-microbial in this context. In the host, the electric field enhanced keratinocyte migration, bolstered immune defenses, improved mitochondrial function, and demonstrated multiple other effects consistent with supporting wound healing. A deeper mechanistic understanding of bioelectrical principles will inform the design of next-generation electroceuticals. Future Directions: This is an opportune moment in time as there is a surge of interest in electroceuticals in medicine. Projected to reach $35.5 billion by 2025, electroceuticals are becoming a cynosure in the global market. The World Health Organization reports that more than 50% of surgical site infections can be antibiotic resistant. Electroceuticals offer a serious alternative.Item Filamentous bacteriophage delays healing of Pseudomonas-infected wounds(Elsevier, 2022) Bach, Michelle S.; de Vries, Christiaan R.; Khosravi, Arya; Sweere, Johanna M.; Popescu, Medeea C.; Chen, Qingquan; Demirdjian, Sally; Hargil, Aviv; Van Belleghem, Jonas D.; Kaber, Gernot; Hajfathalian, Maryam; Burgener, Elizabeth B.; Liu, Dan; Tran, Quynh-Lam; Dharmaraj, Tejas; Birukova, Maria; Sunkari, Vivekananda; Balaji, Swathi; Ghosh, Nandini; Mathew-Steiner, Shomita S.; El Masry, Mohamed S.; Keswani, Sundeep G.; Banaei, Niaz; Nedelec, Laurence; Sen, Chandan K.; Chandra, Venita; Secor, Patrick R.; Suh, Gina A.; Bollyky, Paul L.; Surgery, School of MedicineChronic wounds infected by Pseudomonas aeruginosa (Pa) are characterized by disease progression and increased mortality. We reveal Pf, a bacteriophage produced by Pa that delays healing of chronically infected wounds in human subjects and animal models of disease. Interestingly, impairment of wound closure by Pf is independent of its effects on Pa pathogenesis. Rather, Pf impedes keratinocyte migration, which is essential for wound healing, through direct inhibition of CXCL1 signaling. In support of these findings, a prospective cohort study of 36 human patients with chronic Pa wound infections reveals that wounds infected with Pf-positive strains of Pa are more likely to progress in size compared with wounds infected with Pf-negative strains. Together, these data implicate Pf phage in the delayed wound healing associated with Pa infection through direct manipulation of mammalian cells. These findings suggest Pf may have potential as a biomarker and therapeutic target in chronic wounds.Item Genome-wide DNA hypermethylation opposes healing in patients with chronic wounds by impairing epithelial-mesenchymal transition(The American Society for Clinical Investigation, 2022) Singh, Kanhaiya; Rustagi, Yashika; Abouhashem, Ahmed S.; Tabasum, Saba; Verma, Priyanka; Hernandez, Edward; Pal, Durba; Khona, Dolly K.; Mohanty, Sujit K.; Kumar, Manishekhar; Srivastava, Rajneesh; Guda, Poornachander R.; Verma, Sumit S.; Mahajan, Sanskruti; Killian, Jackson A.; Walker, Logan A.; Ghatak, Subhadip; Mathew-Steiner, Shomita S.; Wanczyk, Kristen E.; Liu, Sheng; Wan, Jun; Yan, Pearlly; Bundschuh, Ralf; Khanna, Savita; Gordillo, Gayle M.; Murphy, Michael P.; Roy, Sashwati; Sen, Chandan K.; Surgery, School of MedicineAn extreme chronic wound tissue microenvironment causes epigenetic gene silencing. An unbiased whole-genome methylome was studied in the wound-edge tissue of patients with chronic wounds. A total of 4,689 differentially methylated regions (DMRs) were identified in chronic wound-edge skin compared with unwounded human skin. Hypermethylation was more frequently observed (3,661 DMRs) in the chronic wound-edge tissue compared with hypomethylation (1,028 DMRs). Twenty-six hypermethylated DMRs were involved in epithelial-mesenchymal transition (EMT). Bisulfite sequencing validated hypermethylation of a predicted specific upstream regulator TP53. RNA-Seq analysis was performed to qualify findings from methylome analysis. Analysis of the downregulated genes identified the TP53 signaling pathway as being significantly silenced. Direct comparison of hypermethylation and downregulated genes identified 4 genes, ADAM17, NOTCH, TWIST1, and SMURF1, that functionally represent the EMT pathway. Single-cell RNA-Seq studies revealed that these effects on gene expression were limited to the keratinocyte cell compartment. Experimental murine studies established that tissue ischemia potently induces wound-edge gene methylation and that 5'-azacytidine, inhibitor of methylation, improved wound closure. To specifically address the significance of TP53 methylation, keratinocyte-specific editing of TP53 methylation at the wound edge was achieved by a tissue nanotransfection-based CRISPR/dCas9 approach. This work identified that reversal of methylation-dependent keratinocyte gene silencing represents a productive therapeutic strategy to improve wound closure.