Electrospray Mediated Localized and Targeted Chemotherapy in a Mouse Model of Lung Cancer.

Background: An advanced stage, centrally localized invasive tumor is a major cause of sudden death in lung cancer patients. Currently, chemotherapy, radiotherapy, laser ablation, or surgical resection if possible are the available state-of-the-art treatments but none of these guarantee remedy or long-term relief and are often associated with fatal complications. Allowing localized chemotherapy, by direct and confined drug delivery only at the tumor site, could be a promising option for preoperative down staging or palliative therapy. Here we report the localized and targeted application of intra tumor delivery of chemotherapeutics using a novel device based on the principle of electrospray. Methods: C57BL/6J mice were injected with Lewis lung carcinoma cells subcutaneously. After 15 days, the animals were anesthetized and the tumors were exposed by skin incision. Tumors were electrosprayed with 100 µg cisplatin on days 0 and 2, and tumor volumes were measured daily. Animals were sacrificed on day 7 after the first electrospray and tumors were analyzed by immunohistochemistry. Results: In this proof-of-concept study, we report that the tumor volume was reduced by 81.2% (22.46 ± 12.14 mm3) after two electrospray mediated Cisplatin deliveries, while the control tumor growth, at the same time point, increased by 200% (514.30 ± 104.50 mm3). Moreover, tunnel and Caspase-3 positive cells were increased after Cisplatin electrospray compared to other experimental groups of animals. Conclusion: Targeted drug delivery by electrospray is efficient in the subcutaneous mouse model of lung cancer and offers a promising opportunity for further development toward its clinical application.

Rapid Prototyping Method for 3D Printed Biomaterial Constructs with Vascular Structures.

This paper presents a fabrication method for rapid prototyping of 3D biomaterial constructs with vascular structures. The method relies on poloxamer fugitive ink, which is over casted with a custom-made alginate based model extracellular matrix (ECM). The presented method is simple to implement and compatible with standard cell culture workflows used in biomedical research and pharmaceutical development. We present the material preparation, gelation properties and printing methods in detail. First experiments demonstrate the suitability of the ECM constructs for 3D tissue culture.

Method for analysis of electrospray for gene transfer and the impact on cell viability of A549 alveolar epithelial like cells.

Electrospray is a process based on creation and acceleration of small sized droplets based on electrostatic repulsion. Spraying plasmid containing liquids this process may be used to transfer genes into cells. Within this paper we report on a method for accessing and evaluating the spray modalities using high speed imaging system with a post processing of image data to obtain estimated volume and velocity of emerging droplets first. Second we investigate on the impact of different media on the spray modalities. Third we evaluate the impact of the spray on cell viability and on transfection efficiency of an eGFP plasmid as reporter gene obtained in an in vitro setup on alveolar epithelial like cells (A549).

A new electrospray method for targeted gene delivery.

A challenge for gene therapy is absence of safe and efficient local delivery of therapeutic genetic material. An efficient and reproducible physical method of electrospray for localized and targeted gene delivery is presented. Electrospray works on the principle of coulombs repulsion, under influence of electric field the liquid carrying genetic material is dispersed into micro droplets and is accelerated towards the targeted tissue, acting as a counter electrode. The accelerated droplets penetrate the targeted cells thus facilitating the transfer of genetic material into the cell. The work described here presents the principle of electrospray for gene delivery, the basic instrument design, and the various optimized parameters to enhance gene transfer in vitro. We estimate a transfection efficiency of up to 60% was achieved. We describe an efficient gene transfer method and a potential electrospray-mediated gene transfer mechanism.

Monitoring the effectiveness of the vacuum bell during pectus excavatum treatment: Technical innovation.

BACKGROUND: The vacuum bell (VB) is a valid and the only non-invasive treatment for pectus excavatum (PE). To elevate the sternum the patient himself creates a differential negative pressure inside the VB using a hand pump. A distance and differential pressure measuring device (DPMD) enables us for the first time to assess objectively those parameters. METHODS: After approval by the institutional review board, 53 patients recruited from our outpatient clinic were included in this retrospective study and distributed into three groups (group 1 aged 6 to 10years; group 2 aged 11 to 15years; group 3 aged 16 to 20years). Sternum elevation and differential negative pressure inside the VB compared to atmospheric pressure were assessed with the DPMD, a device developed by engineers at the University of Applied Sciences, Northwestern Switzerland. Pressure-elevation curves were recorded during VB therapy. For statistical comparison of the groups, analysis of variance was used. Post-hoc analysis was performed using the Tukey-Kramer test. A p-value of less than 0.05 was considered to be statistically significant. RESULTS: The VB therapy was monitored in 53 children (39 males, 14 females) aged from 6 to 20years (average, 14years). Relationships were established between the differential negative pressure inside the vacuum bell, the elevation of the sternum, and the patient's age. The younger the patient, the lower is the differential negative pressure difference required to obtain a complete elevation of the sternum. Patient's age, weight, the pectus depth, the differential negative pressure inside the VB, and the elevation of the sternum were correlated. When comparing the depth 25 of the pectus excavatum to the patient's age, a statistically significant difference was verified between the groups 3 and 1 (p=0.0291) and 3 and 2 (p=0.0489). The older the patient, the deeper is the pectus excavatum. However, no statistically significant difference between the groups was found when comparing the sternum elevation to the patient's age (p=0.4574) and the elevation to pressure ratio to the patient's age (p=0.8048). The sternum elevation and the elevation to pressure ratio are independent of the patient's age. CONCLUSIONS: DPMD supplies objective data of the elevation of the sternum and the related pressure inside the VB during its application. Correlation between the patient's age, the elevation of the sternum and the pressure inside the VB were demonstrated, but additional data are needed to better understand their relationship and their impact in the treatment of PE by VB. STUDY TYPE: Diagnostic Study. LEVEL OF EVIDENCE: IV.

Capacitive on-line hematocrit sensor design based on impedance spectroscopy for use in hemodialysis machines.

This paper presents a new design for an on-line and in-line hematocrit (HCT) sensor. Special feature of the sensor is the capability to measure the hematocrit of a blood sample inside standard plastic tubing widely used in medical equipment. No blood sample has to be extracted out of existing extracorporeal blood circulation systems such as hemodialysis machines or heart-lung machines. The sensor principle is based on electrical impedance spectroscopy. Dielectric properties of the blood and the plastic tubing are measured at various frequencies. In order to optimize the sensitivity, a unique electrode configuration is developed and optimized by Finite Element Simulation. The new electrode design optimizes the overall sensitivity of the sensor towards a change in dielectric properties of the blood caused by the HCT value and therefore decreases the sensitivity to side effects caused by temperature drift and component tolerances. As a result of the optimized overall sensor performance the complexity of a sensor readout circuitry can be reduced to a minimum which leads to an unmatched price-performance ratio for a complete measurement system.