Joshua A. Samuels

Antimicrobial efficacy and wound-healing property of a topical ointment containing nitric-oxide-loaded zeolites.

Topical delivery of nitric oxide (NO) through a wound dressing has the potential to reduce wound infections and improve healing of acute and chronic wounds. This study characterized the antibacterial efficacy of an ointment containing NO-loaded, zinc-exchanged zeolite A that releases NO upon contact with water. The release rate of NO from the ointment was measured using a chemiluminescence detection system. Minimum bactericidal concentration assays were performed using five common wound pathogens, including Gram-negative bacteria (Escherichia coli and Acinetobacter baumannii), Gram-positive bacteria (Staphylococcus epidermidis and meticillin-resistant Staphylococcus aureus) and a fungus (Candida albicans). The time dependence of antimicrobial activity was characterized by performing log-reduction assays at four time points after 1-8 h ointment exposure. The cytotoxicity of the ointment after 24 h was assessed using cultured 3T3 fibroblast cells. Minimum microbicidal concentrations (MMCs) for bacterial organisms (5×10(7) c.f.u.) ranged from 50 to 100 mg ointment (ml media)(-1); the MMC for C. albicans (5×10(4) c.f.u.) was 50 mg ointment (ml media)(-1). Five to eight log reductions in bacterial viability and three log reductions in fungal viability were observed after 8 h exposure to NO-zeolite ointment compared with untreated organisms. Fibroblasts remained viable after 24 h exposure to the same concentration of NO-zeolite ointment as was used in antimicrobial tests. In parallel studies, full-thickness cutaneous wounds on Zucker obese rats healed faster than wounds treated with a control ointment. These data indicate that ointment containing NO-loaded zeolites could potentially be used as a broad-spectrum antimicrobial wound-healing dressing.

Low-frequency (<100 kHz), low-intensity (<100 mW/cm2) ultrasound to treat venous ulcers: A human study and in vitro experiments

The purpose of this study was to examine whether low frequency (<100 kHz), low intensity (<100 mW/cm(2), spatial peak temporal peak) ultrasound can be an effective treatment of venous stasis ulcers, which affect 500 000 patients annually costing over

Optimization of un-tethered, low voltage, 20-100kHz flexural transducers for biomedical ultrasonics applications.

1 billion per year. Twenty subjects were treated with either 20 or 100 kHz ultrasound for between 15 and 45 min per session for a maximum of four treatments. Healing was monitored by changes in wound area. Additionally, two in vitro studies were conducted using fibroblasts exposed to 20 kHz ultrasound to confirm the ultrasounds effects on proliferation and cellular metabolism. Subjects receiving 20 kHz ultrasound for 15 min showed statistically faster (p < 0.03) rate of wound closure. All five of these subjects fully healed by the fourth treatment session. The in vitro results indicated that 20 kHz ultrasound at 100 mW/cm(2) caused an average of 32% increased metabolism (p < 0.05) and 40% increased cell proliferation (p < 0.01) after 24 h when compared to the control, non-treated cells. Although statistically limited, this work supports the notion that low-intensity, low-frequency ultrasound is beneficial for treating venous ulcers.

Finite element static displacement optimization of 20–100 kHz flexural transducers for fully portable ultrasound applicator

This paper describes optimization of un-tethered, low voltage, 20-100kHz flexural transducers for biomedical ultrasonics applications. The goal of this work was to design a fully wearable, low weight (<100g), battery operated, piezoelectric ultrasound applicator providing maximum output pressure amplitude at the minimum excitation voltage. Such implementation of ultrasound applicators that can operate at the excitation voltages on the order of only 10-25V is needed in view of the emerging evidence that spatial-peak temporal-peak ultrasound intensity (I(SPTP)) on the order of 100mW/cm(2) delivered at frequencies below 100kHz can have beneficial therapeutic effects. The beneficial therapeutic applications include wound management of chronic ulcers and non-invasive transdermal delivery of insulin and liposome encapsulated drugs. The early prototypes of the 20 and 100kHz applicators were optimized using the maximum electrical power transfer theorem, which required a punctilious analysis of the complex impedance of the piezoelectric disks mounted in appropriately shaped metal housings. In the implementation tested, the optimized ultrasound transducer applicators were driven by portable, customized electronics, which controlled the excitation voltage amplitude and facilitated operation in continuous wave (CW) or pulsed mode with adjustable (10-90%) duty cycle. The driver unit was powered by remotely located rechargeable lithium (Li) polymer batteries. This was done to further minimize the weight of the applicator unit making it wearable. With DC voltage of approximately 15V the prototypes were capable of delivering pressure amplitudes of about 55kPa or 100mW/cm(2) (I(SPTP)). This level of acoustic output was chosen as it is considered safe and side effects free, even at prolonged exposure.

Diffuse near-infrared spectroscopy prediction of healing in diabetic foot ulcers: A human study and cost analysis

This paper focuses on the development of a finite-element model and subsequent stationary analysis performed to optimize individual flexural piezoelectric elements for operation in the frequency range of 20-100kHz. These elements form the basic building blocks of a viable, un-tethered, and portable ultrasound applicator that can produce intensities on the order of 100mW/cm(2) spatial-peak temporal-peak (I(SPTP)) with minimum (on the order of 15V) excitation voltage. The ultrasound applicator can be constructed with different numbers of individual transducer elements and different geometries such that its footprint or active area is adjustable. The primary motivation behind this research was to develop a tether-free, battery operated, fully portable ultrasound applicator for therapeutic applications such as wound healing and non-invasive transdermal delivery of both naked and encapsulated drugs. It is shown that careful selection of the components determining applicator architecture allows the displacement amplitude to be maximized for a specific frequency of operation. The work described here used the finite-element analysis software COMSOL to identify the geometry and material properties that permit the applicators design to be optimized. By minimizing the excitation voltage required to achieve the desired output (100mW/cm(2)I(SPTP)) the power source (rechargeable Li-Polymer batteries) size may be reduced permitting both the electronics and ultrasound applicator to fit in a wearable housing.

Development of a multi-frequency diffuse photon density wave device for the characterization of tissue damage at multiple depths

Wound size reduction has been the standard benchmark for determination of efficacy for diabetic ulcer treatments but due to interclinician error and difficulty measuring irregular wound shapes, this method is unreliable with a positive predictive value of less than 60%. Diffuse near‐infrared spectroscopy (DNIRS) uses 70‐MHz modulated light in the diagnostic window (650–900 nm) noninvasively to quantify levels of oxy‐ and deoxy‐hemoglobin in the wound bed, which when measured over time, can show a trend toward or away from healing based on the changes in oxy‐hemoglobin concentration from week to week. In this study, DNIRS was used to monitor 24 human diabetic foot ulcers longitudinally over the course of 20 weekly or biweekly measurement sessions. In just 4 weeks, the DNIRS system has an 82% positive predictive value (sensitivity of 0.9 and specificity of 0.86; p < 0.002). These data indicate that it could be possible to predict healing in 4 weeks using DNIRS, which can provide objective guidance toward the continuation of costly treatments. Discontinuing ineffective treatments after 4 weeks could have potentially saved over

Ultrasound for healing chronic wounds

12,600 per patient, based on the treatment regimen of patients in this study.

Low intensity (55 kPa) 20 kHz ultrasound heals venous ulcers

The ability to determine the depth and degree of cutaneous and subcutaneous tissue damage is critical for medical applications such as burns and pressure ulcers. The Diffuse Photon Density Wave (DPDW) methodology at near infrared wavelengths can be used to non-invasively measure the optical absorption and reduced scattering coefficients of tissue at depths of several millimeters. A multi-frequency DPDW system with one light source and one detector was constructed so that light is focused onto the tissue surface using an optical fiber and lens mounted to a digitally-controlled actuator which changes the distance between light source and detector. A variable RF generator enables the modulation frequency to be selected between 50 to 400MHz. The ability to digitally control both source-detector separation distance and modulation frequency allows for virtually unlimited number of data points, enabling precise selection of the volume and depth of tissue that will be characterized. Suspensions of Intralipid and india ink with known absorption and reduced scattering coefficients were used as optical phantoms to assess device accuracy. Solid silicon phantoms were formulated for stability testing. Standard deviations for amplitude and phase shift readings were found to be 0.9% and 0.2 degrees respectively, over a one hour period. The ability of the system to quantify tissue damage in vivo at multiple depths was tested in a porcine burn model.

Diffuse Correlation Spectroscopy to Assess Capillary Flow Relative to Vascular Disease and Cigarette Smoking

Over 500,000 patients are treated for venous ulcers annually, accounting for approximately 1% of total healthcare costs in the western world.1, 2 Direct wound care costs often exceed

20—100 kHz, ultrasound assisted treatment of chronic wounds

2,400 per month,1, 2 but despite this, the pain and resulting limitations on mobility and productivity mean venous ulcers force many patients to give up work. Not only does this create an economic drain, but it can potentially lead to further costs associated with anxiety and depression.3 Hence, even modest reductions in healing time could reduce healthcare costs significantly. The ideal solution could be used at home by patients, reducing hospital visits for patients with limited mobility and providing moreconvenient treatment for chronic wounds. We recruited 16 patients between the ages of 18 and 80 years and with chronic venous ulcers from Drexel University Wound Healing Center for a trial of ultrasound treatment of their wounds with concurrent optical monitoring. Eligibility included having had a documented venous ulcer for at least 8 weeks with a surface area 1cm2 using a standard calculation of length width.4 Furthermore, patients with moderate to severe vascular insufficiency (ankle brachial index <0.75 or toe brachial index <0.5) were excluded, as tissue oxygen perfusion and subsequent wound healing are known to be diminished in these individuals.5 Patients with invasive bacterial infection or on antibiotics were also excluded. Following enrolment, the subjects were randomly assigned to one of two experimental groups: active ultrasound treatment or treatment with a sham applicator. Treatment sessions lasted 15 minutes and were conducted once a week for a period of 12 treatments, or until closure. Throughout the study, all subjects received standard wound care that included weekly or Figure 1. The ultrasound applicator used during the clinical study.