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Article: Nanoscopic and Functional Characterization of Keratinocyte-Originating Exosomes in the Wound Fluid of Non-Diabetic and Diabetic Chronic Wound Patients.

Guda, Poornachander R / Sharma, Anu / Anthony, Adam J / ElMasry, Mohamed S / Couse, Andrew D / Ghatak, Piya Das / Das, Amitava / Timsina, Lava / Trinidad, Jonathan C / Roy, Sashwati / Clemmer, David E / Sen, Chandan K / Ghatak, Subhadip

Nano today

2023 Volume 52

Abstract: Exosomes, a class of extracellular vesicles of endocytic origin, play a critical role in paracrine signaling for successful cell-cell ... ...

Abstract	Exosomes, a class of extracellular vesicles of endocytic origin, play a critical role in paracrine signaling for successful cell-cell crosstalk
Language	English
Publishing date	2023-08-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2224882-1
ISSN	1878-044X ; 1748-0132
ISSN (online)	1878-044X
ISSN	1748-0132
DOI	10.1016/j.nantod.2023.101954
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Article ; Online: Use of antibiotic impregnated resorbable beads reduces pressure ulcer recurrence: A retrospective analysis.

Khansa, Ibrahim / Barker, Jenny C / Ghatak, Piya Das / Sen, Chandan K / Gordillo, Gayle M

Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society

2018 Volume 26, Issue 2, Page(s) 221–227

Abstract: Recurrence of pressure ulcers remains common. We have employed resorbable antibiotic beads as a therapeutic strategy to deliver high local antibiotic concentrations to the debridement site. Our objective was to determine whether the use of resorbable ... ...

Abstract	Recurrence of pressure ulcers remains common. We have employed resorbable antibiotic beads as a therapeutic strategy to deliver high local antibiotic concentrations to the debridement site. Our objective was to determine whether the use of resorbable antibiotic- beads would reduce pressure ulcer recurrence. We reviewed all stage IV pressure ulcers treated with excision, partial ostectomy and flap coverage over 16 years. Baseline patient factors (location of ulcer, presence of osteomyelitis, preoperative prealbumin), surgical factors (type of flap, use of antibiotic beads, bone culture results) and postoperative outcomes (ulcer recurrence at 1 year, dehiscence, seroma, cellulitis) were collected. Outcomes of patients who received antibiotic-impregnated beads were compared to those who did not. Eighty-six patients with 120 stage IV pressure ulcers underwent excision and flap coverage. This included 16 ulcers where antibiotic beads were used and 104 where they were not. The overall ulcer recurrence rate at 12 months was 35.8%. The recurrence rate in the group treated with antibiotic beads was significantly lower than the group without beads (12.5% vs. 39.4%, p = 0.03). Overall, complication rates between the two groups were similar (43.8% vs. 51.9%, p = 0.54). No systemic or local toxicity from antibiotic beads occurred. Scanning electron microscopy images of sacral bone from one case showed bacterial biofilm even after debridement. Pressure ulcer recurrence at 1 year after excision and flap coverage decreased significantly with the use of resorbable antibiotic beads.
MeSH term(s)	Anti-Bacterial Agents/administration & dosage ; Debridement/methods ; Humans ; Infusion Pumps, Implantable ; Osteomyelitis/complications ; Osteomyelitis/prevention & control ; Osteomyelitis/therapy ; Postoperative Care/methods ; Postoperative Complications/drug therapy ; Postoperative Complications/pathology ; Postoperative Complications/prevention & control ; Pressure Ulcer/pathology ; Pressure Ulcer/prevention & control ; Pressure Ulcer/therapy ; Reconstructive Surgical Procedures ; Recurrence ; Retrospective Studies ; Surgical Flaps ; Treatment Outcome
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2018-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1174873-4
ISSN	1524-475X ; 1067-1927
ISSN (online)	1524-475X
ISSN	1067-1927
DOI	10.1111/wrr.12638
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Article: Power Generation for Wearable Electronics: Designing Electrochemical Storage on Fabrics.

Vilkhu, Ramandeep / Thio, Wesley Joo-Chen / Ghatak, Piya Das / Sen, Chandan K / Co, Anne C / Kiourti, Asimina

IEEE access : practical innovations, open solutions

2018 Volume 6, Page(s) 28945–28950

Abstract: We report a new class of textiles with electrochemical functions which, when moistened by a conductive liquid (saline solution, sweat, wound fluid, etc.), generate DC voltage and current levels capable of powering wearable electronics on the go. Contrary ...

Abstract	We report a new class of textiles with electrochemical functions which, when moistened by a conductive liquid (saline solution, sweat, wound fluid, etc.), generate DC voltage and current levels capable of powering wearable electronics on the go. Contrary to previously reported power generation techniques, the proposed fabrics are fully flexible, feel and behave like regular clothing, do not include any rigid components, and provide DC power via moistening by readily available liquids. Our approach entails printed battery cells that are composed of silver and zinc electrodes deposited onto a polyester fabric to generate power in the microwatt range. Electrochemical characterization of the discharge of a single printed battery cell in a 10 M NaOH electrolyte shows reproducible results with a sustained power level of ∼80
Language	English
Publishing date	2018-05-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2687964-5
ISSN	2169-3536
ISSN	2169-3536
DOI	10.1109/ACCESS.2018.2839078
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Article ; Online: May Dietary Supplementation Augment Respiratory Burst in Wound-Site Inflammatory Cells?

Das, Amitava / Dickerson, Ryan / Ghatak, Piya Das / Gordillo, Gayle M / Chaffee, Scott / Saha, Abhijoy / Khanna, Savita / Roy, Sashwati

Antioxidants & redox signaling

2017 Volume 28, Issue 5, Page(s) 401–405

Abstract: Persistent infection contributes to wound chronicity. At the wound site, NADPH oxidase (NOX) activity in immune cells fights infection to enable the healing process. Fermented papaya preparation (FPP) is a carbohydrate-rich nutritional supplement that ... ...

Abstract	Persistent infection contributes to wound chronicity. At the wound site, NADPH oxidase (NOX) activity in immune cells fights infection to enable the healing process. Fermented papaya preparation (FPP) is a carbohydrate-rich nutritional supplement that has demonstrated ability to bolster respiratory burst in experimental rodent systems. In FPP, glucose coexists with fructose and maltose in addition to multiple other sugar alcohols such as inositol. We have previously reported that FPP supplementation augments wound healing in diabetic mice via improvement of respiratory burst activity of wound innate immune cells. In this clinical study ( clinicaltrials.gov : NCT02332993), chronic wound patients were orally supplemented with FPP daily. Inducible production of reactive oxygen species was significantly higher in wound-site immune cells from patients supplemented with FPP and on standard of care (SoC) for wound management compared with those patients receiving SoC alone. Wound closure in FPP-supplemented patients showed improvement. Importantly, the consumption of this mixture of carbohydrates, including significant amounts of glucose, did not increase HbA1c. These observations warrant a full-length clinical trial testing the hypothesis that FPP improves wound closure by augmenting NOX activity in immune cells at the wound site. Antioxid. Redox Signal. 28, 401-405.
MeSH term(s)	Antioxidants/administration & dosage ; Dietary Supplements ; Female ; Humans ; Male ; Middle Aged ; Oxidation-Reduction ; Plant Preparations/administration & dosage ; Reactive Oxygen Species/metabolism ; Respiratory Burst/drug effects ; Wound Healing/drug effects
Chemical Substances	Antioxidants ; Plant Preparations ; Reactive Oxygen Species ; fermented papaya preparation
Language	English
Publishing date	2017-10-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1483836-9
ISSN	1557-7716 ; 1523-0864
ISSN (online)	1557-7716
ISSN	1523-0864
DOI	10.1089/ars.2017.7304
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Article: A Wireless Electroceutical Dressing Lowers Cost of Negative Pressure Wound Therapy.

Ghatak, Piya Das / Schlanger, Richard / Ganesh, Kasturi / Lambert, Lynn / Gordillo, Gayle M / Martinsek, Patsy / Roy, Sashwati

Advances in wound care

2015 Volume 4, Issue 5, Page(s) 302–311

Abstract: Objective: ...

Abstract	Objective:
Language	English
Publishing date	2015-05-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2650541-1
ISSN	2162-1934 ; 2162-1918
ISSN (online)	2162-1934
ISSN	2162-1918
DOI	10.1089/wound.2014.0615
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Article ; Online: Staphylococcus aureus Biofilm Infection Compromises Wound Healing by Causing Deficiencies in Granulation Tissue Collagen.

Roy, Sashwati / Santra, Suman / Das, Amitava / Dixith, Sriteja / Sinha, Mithun / Ghatak, Subhadip / Ghosh, Nandini / Banerjee, Pradipta / Khanna, Savita / Mathew-Steiner, Shomita / Ghatak, Piya Das / Blackstone, Britani N / Powell, Heather M / Bergdall, Valerie K / Wozniak, Daniel J / Sen, Chandan K

Annals of surgery

2019 Volume 271, Issue 6, Page(s) 1174–1185

Abstract: Objective: The objective of this work was to causatively link biofilm properties of bacterial infection to specific pathogenic mechanisms in wound healing.: Background: Staphylococcus aureus is one of the four most prevalent bacterial species ... ...

Abstract	Objective: The objective of this work was to causatively link biofilm properties of bacterial infection to specific pathogenic mechanisms in wound healing. Background: Staphylococcus aureus is one of the four most prevalent bacterial species identified in chronic wounds. Causatively linking wound pathology to biofilm properties of bacterial infection is challenging. Thus, isogenic mutant stains of S. aureus with varying degree of biofilm formation ability was studied in an established preclinical porcine model of wound biofilm infection. Methods: Isogenic mutant strains of S. aureus with varying degree (ΔrexB > USA300 > ΔsarA) of biofilm-forming ability were used to infect full-thickness porcine cutaneous wounds. Results: Compared with that of ΔsarA infection, wound biofilm burden was significantly higher in response to ΔrexB or USA300 infection. Biofilm infection caused degradation of cutaneous collagen, specifically collagen 1 (Col1), with ΔrexB being most pathogenic in that regard. Biofilm infection of the wound repressed wound-edge miR-143 causing upregulation of its downstream target gene matrix metalloproteinase-2. Pathogenic rise of collagenolytic matrix metalloproteinase-2 in biofilm-infected wound-edge tissue sharply decreased collagen 1/collagen 3 ratio compromising the biomechanical properties of the repaired skin. Tensile strength of the biofilm infected skin was compromised supporting the notion that healed wounds with a history of biofilm infection are likely to recur. Conclusion: This study provides maiden evidence that chronic S. aureus biofilm infection in wounds results in impaired granulation tissue collagen leading to compromised wound tissue biomechanics. Clinically, such compromise in tissue repair is likely to increase wound recidivism.
MeSH term(s)	Animals ; Biofilms ; Cells, Cultured ; Collagen/metabolism ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Granulation Tissue/metabolism ; Granulation Tissue/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Staphylococcal Infections/microbiology ; Staphylococcus aureus/isolation & purification ; Swine ; Wound Healing/physiology ; Wound Infection/diagnosis ; Wound Infection/microbiology
Chemical Substances	Collagen (9007-34-5)
Language	English
Publishing date	2019-01-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	340-2
ISSN	1528-1140 ; 0003-4932
ISSN (online)	1528-1140
ISSN	0003-4932
DOI	10.1097/SLA.0000000000003053
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Article ; Online: Electric Field Based Dressing Disrupts Mixed-Species Bacterial Biofilm Infection and Restores Functional Wound Healing.

Barki, Kasturi Ganesh / Das, Amitava / Dixith, Sriteja / Ghatak, Piya Das / Mathew-Steiner, Shomita / Schwab, Elizabeth / Khanna, Savita / Wozniak, Daniel J / Roy, Sashwati / Sen, Chandan K

Annals of surgery

2017 Volume 269, Issue 4, Page(s) 756–766

Abstract: Objective: This study was designed to employ electroceutical principles, as an alternative to pharmacological intervention, to manage wound biofilm infection. Mechanism of action of a United States Food and Drug Administration-cleared wireless ... ...

Abstract	Objective: This study was designed to employ electroceutical principles, as an alternative to pharmacological intervention, to manage wound biofilm infection. Mechanism of action of a United States Food and Drug Administration-cleared wireless electroceutical dressing (WED) was tested in an established porcine chronic wound polymicrobial biofilm infection model involving inoculation with Pseudomonas aeruginosa PAO1 and Acinetobacter baumannii 19606. Background: Bacterial biofilms represent a major wound complication. Resistance of biofilm toward pharmacologic interventions calls for alternative therapeutic strategies. Weak electric field has anti-biofilm properties. We have previously reported the development of WED involving patterned deposition of Ag and Zn on fabric. When moistened, WED generates a weak electric field without any external power supply and can be used as any other disposable dressing. Methods: WED dressing was applied within 2 hours of wound infection to test its ability to prevent biofilm formation. Alternatively, WED was applied after 7 days of infection to study disruption of established biofilm. Wounds were treated with placebo dressing or WED twice a week for 56 days. Results: Scanning electron microscopy demonstrated that WED prevented and disrupted wound biofilm aggregates. WED accelerated functional wound closure by restoring skin barrier function. WED blunted biofilm-induced expression of (1) P. aeruginosa quorum sensing mvfR (pqsR), rhlR and lasR genes, and (2) miR-9 and silencing of E-cadherin. E-cadherin is critically required for skin barrier function. Furthermore, WED rescued against biofilm-induced persistent inflammation by circumventing nuclear factor kappa B activation and its downstream cytokine responses. Conclusion: This is the first pre-clinical porcine mechanistic study to recognize the potential of electroceuticals as an effective platform technology to combat wound biofilm infection.
MeSH term(s)	Animals ; Bandages ; Biofilms ; Electricity ; Equipment Design ; Female ; Swine ; Wound Healing ; Wound Infection/therapy
Language	English
Publishing date	2017-10-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	340-2
ISSN	1528-1140 ; 0003-4932
ISSN (online)	1528-1140
ISSN	0003-4932
DOI	10.1097/SLA.0000000000002504
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Article ; Online: A modified collagen gel dressing promotes angiogenesis in a preclinical swine model of chronic ischemic wounds.

Elgharably, Haytham / Ganesh, Kasturi / Dickerson, Jennifer / Khanna, Savita / Abas, Motaz / Ghatak, Piya Das / Dixit, Sriteja / Bergdall, Valerie / Roy, Sashwati / Sen, Chandan K

Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society

2015 Volume 22, Issue 6, Page(s) 720–729

Abstract: We recently performed proteomic characterization of a modified collagen gel (MCG) dressing and reported promising effects of the gel in healing full-thickness excisional wounds. In this work, we test the translational relevance of our aforesaid findings ... ...

Abstract	We recently performed proteomic characterization of a modified collagen gel (MCG) dressing and reported promising effects of the gel in healing full-thickness excisional wounds. In this work, we test the translational relevance of our aforesaid findings by testing the dressing in a swine model of chronic ischemic wounds recently reported by our laboratory. Full-thickness excisional wounds were established in the center of bipedicle ischemic skin flaps on the backs of animals. Ischemia was verified by laser Doppler imaging, and MCG was applied to the test group of wounds. Seven days post wounding, macrophage recruitment to the wound was significantly higher in MCG-treated ischemic wounds. In vitro, MCG up-regulated expression of Mrc-1 (a reparative M2 macrophage marker) and induced the expression of anti-inflammatory cytokine interleukin (IL)-10 and of fibroblast growth factor-basic (β-FGF). An increased expression of CCR2, an M2 macrophage marker, was noted in the macrophages from MCG treated wounds. Furthermore, analyses of wound tissues 7 days post wounding showed up-regulation of transforming growth factor-β, vascular endothelial growth factor, von Willebrand's factor, and collagen type I expression in MCG-treated ischemic wounds. At 21 days post wounding, MCG-treated ischemic wounds displayed higher abundance of proliferating endothelial cells that formed mature vascular structures and increased blood flow to the wound. Fibroblast count was markedly higher in MCG-treated ischemic wound-edge tissue. In addition, MCG-treated wound-edge tissues displayed higher abundance of mature collagen with increased collagen type I : III deposition. Taken together, MCG helped mount a more robust inflammatory response that resolved in a timely manner, followed by an enhanced proliferative phase, angiogenic outcome, and postwound tissue remodeling. Findings of the current study warrant clinical testing of MCG in a setting of ischemic chronic wounds.
MeSH term(s)	Angiogenesis Inducing Agents/pharmacology ; Animals ; Bandages ; Chronic Disease ; Collagen/pharmacology ; Disease Models, Animal ; Gels ; Immunohistochemistry ; Ischemia/complications ; Surgical Flaps ; Swine ; Vascular Endothelial Growth Factor A/metabolism ; Wound Healing ; Wounds and Injuries/etiology ; Wounds and Injuries/pathology ; Wounds and Injuries/therapy
Chemical Substances	Angiogenesis Inducing Agents ; Gels ; Vascular Endothelial Growth Factor A ; Collagen (9007-34-5)
Language	English
Publishing date	2015-01-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1174873-4
ISSN	1524-475X ; 1067-1927
ISSN (online)	1524-475X
ISSN	1067-1927
DOI	10.1111/wrr.12229
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Article ; Online: First evidence of sternal wound biofilm following cardiac surgery.

Elgharably, Haytham / Mann, Ethan / Awad, Hamdy / Ganesh, Kasturi / Ghatak, Piya Das / Gordillo, Gayle / Sai-Sudhakar, Chittoor B / Roy, Sashwati / Wozniak, Daniel J / Sen, Chandan K

PloS one

2013 Volume 8, Issue 8, Page(s) e70360

Abstract: Management of deep sternal wound infection (SWI), a serious complication after cardiac surgery with high morbidity and mortality incidence, requires invasive procedures such as, debridement with primary closure or myocutaneous flap reconstruction along ... ...

Abstract	Management of deep sternal wound infection (SWI), a serious complication after cardiac surgery with high morbidity and mortality incidence, requires invasive procedures such as, debridement with primary closure or myocutaneous flap reconstruction along with use of broad spectrum antibiotics. The purpose of this clinical series is to investigate the presence of biofilm in patients with deep SWI. A biofilm is a complex microbial community in which bacteria attach to a biological or non-biological surface and are embedded in a self-produced extracellular polymeric substance. Biofilm related infections represent a major clinical challenge due to their resistance to both host immune defenses and standard antimicrobial therapies. Candidates for this clinical series were patients scheduled for a debridement procedure of an infected sternal wound after a cardiac surgery. Six patients with SWI were recruited in the study. All cases had marked dehiscence of all layers of the wound down to the sternum with no signs of healing after receiving broad spectrum antibiotics post-surgery. After consenting patients, tissue and/or extracted stainless steel wires were collected during the debridement procedure. Debrided tissues examined by Gram stain showed large aggregations of Gram positive cocci. Immuno-fluorescent staining of the debrided tissues using a specific antibody against staphylococci demonstrated the presence of thick clumps of staphylococci colonizing the wound bed. Evaluation of tissue samples with scanning electron microscope (SEM) imaging showed three-dimensional aggregates of these cocci attached to the wound surface. More interestingly, SEM imaging of the extracted wires showed attachment of cocci aggregations to the wire metal surface. These observations along with the clinical presentation of the patients provide the first evidence that supports the presence of biofilm in such cases. Clinical introduction of the biofilm infection concept in deep SWI may advance the current management strategies from standard antimicrobial therapy to anti-biofilm strategy.
MeSH term(s)	Adult ; Aged, 80 and over ; Biofilms/drug effects ; Biofilms/growth & development ; Drug Resistance, Bacterial ; Female ; Humans ; Male ; Methicillin-Resistant Staphylococcus aureus/drug effects ; Methicillin-Resistant Staphylococcus aureus/physiology ; Middle Aged ; Sternum/microbiology ; Surgical Wound Infection/microbiology ; Thoracic Surgery ; Tobramycin/pharmacology
Chemical Substances	Tobramycin (VZ8RRZ51VK)
Language	English
Publishing date	2013-08-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0070360
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