Biomedical Engineering and Bioengineering Commons^™

In Vitro And In Vivo Correlation Of Skin And Cellular Responses To Nucleic Acid Delivery, M. Bosnjak, K. Znidar, A. Sales Conniff, T. Jesenko, B. Markelc, Nina Semenova, J. Tur, K. Kohena, S. Kranjc Brezar, L. Heller, M. Cemazar

Bioelectrics Publications

Skin, the largest organ in the body, provides a passive physical barrier against infection and contains elements of the innate and adaptive immune systems. Skin consists of various cells, including keratinocytes, fibroblasts, endothelial cells and immune cells. This diversity of cell types could be important to gene therapies because DNA transfection could elicit different responses in different cell types. Previously, we observed the upregulation and activation of cytosolic DNA sensing pathways in several non-tumor and tumor cell types as well in tumors after the electroporation (electrotransfer) of plasmid DNA (pDNA). Based on this research and the innate immunogenicity of …

Flash Radiotherapy: Skin Pigmentation As A Non-Invasive Indicator For Radiation-Induced Damage, Brady Mccallister

ENGS 88 Honors Thesis (AB Students)

FLASH ultra-high dose rate radiotherapy (RT) is one of the most rapidly growing subfields of radiation oncology today due to its potential to increase the limits of the therapeutic ratio. The FLASH effect, which includes heightened normal tissue sparing paired with iso-effective tumor cell killing, has been literature documented, in a limited manner, in rodent models, a few large animals, and one clinical patients.

A porcine-based experiment was conducted to test the effects of FLASH RT on normal tissue compared to conventional (CONV) RT. A clinical linear accelerator (LINAC) was reversibly converted to be capable of FLASH RT. A female …

Radiotherapy-Induced Cherenkov Luminescence Imaging In A Human Body Phantom, Syed Rakin Ahmed, Mengyu Jia, Petr Bruza, Sergei A. Vinogradov, Shudong Jiang, David J. Gladstone, Lesley A. Jarvis, Brian W. Pogue

Dartmouth Scholarship

Radiation therapy produces Cherenkov optical emission in tissue, and this light can be utilized to activate molecular probes. The feasibility of sensing luminescence from a tissue molecular oxygen sensor from within a human body phantom was examined using the geometry of the axillary lymph node region. Detection of regions down to 30-mm deep was feasible with submillimeter spatial resolution with the total quantity of the phosphorescent sensor PtG4 near 1 nanomole. Radiation sheet scanning in an epi-illumination geometry provided optimal coverage, and maximum intensity projection images provided illustration of the concept. This work provides the preliminary information needed to attempt …

Polysaccharide Fabrication Platforms And Biocompatibility Assessment As Candidate Wound Dressing Materials, Donald C. Aduba Jr., Hu Yang

Chemical and Biochemical Engineering Faculty Research & Creative Works

Wound dressings are critical for wound care because they provide a physical barrier between the injury site and outside environment, preventing further damage or infection. Wound dressings also manage and even encourage the wound healing process for proper recovery. Polysaccharide biopolymers are slowly becoming popular as modern wound dressings materials because they are naturally derived, highly abundant, inexpensive, absorbent, non-toxic and non-immunogenic. Polysaccharide biopolymers have also been processed into biomimetic platforms that offer a bioactive component in wound dressings that aid the healing process. This review primarily focuses on the fabrication and biocompatibility assessment of polysaccharide materials. Specifically, fabrication platforms …

Electro-Gene Transfer To Skin Using A Noninvasive Multielectrode Array, Siqi Guo, Amy Donate, Gaurav Basu, Cathryn Lundberg, Loree Heller, Richard Heller

Bioelectrics Publications

Because of its large surface area and easy access for both delivery and monitoring, the skin is an attractive target for gene therapy for cutaneous diseases, vaccinations and several metabolic disorders. The critical factors for DNA delivery to the skin by electroporation (EP) are effective expression levels and minimal or no tissue damage. Here, we evaluated the non-invasive multielectrode array (MEA) for gene electrotransfer. For these studies we utilized a guinea pig model, which has been shown to have a similar thickness and structure to human skin. Our results demonstrate significantly increased gene expression 2 to 3 logs above injection …

Electrically Mediated Delivery Of Plasmid Dna To The Skin, Using A Multielectrode Array, Richard Heller, Yolmari Criz, Loree C. Heller, Richard A. Gilbert, Mark J. Jaroszeski

Bioelectrics Publications

The easy accessibility of skin makes it an excellent target for gene transfer protocols. To take full advantage of skin as a target for gene transfer, it is important to establish an efficient and reproducible delivery system. Electroporation is a strong candidate to meet this delivery criterion. Electroporation of the skin is a simple, direct, in vivo method to deliver genes for therapy. Previously, delivery to the skin was performed by means of applicators with relatively large distances between electrodes, resulting in significant muscle stimulation and pain. These applicators also had limitations in controlling the directionality of the applied field. …

Biomedical Technology: Supporting Movement, Petros Katsioloudis

STEMPS Faculty Publications

According to the National Institute on Disability and Rehabilitation Research, an estimated 8.5 million children 21 years and younger have a disability (Jans & Stoddard, 1999). After about a decade, with the development of new and sophisticated materials (aluminum alloys, titanium alloys, and carbon fibers) and the integration of electronics, it was then possible to significantly improve the performance of prostheses, built with the so-called endo skeletal (or skeletal-modular) method (Mora, Beratni & Pedrotti, 2006).

Comparison Of Electrically Mediated And Liposome-Complexed Plasmid Dna Delivery To The Skin, Loree C. Heller, Mark J. Jaroszeski, Domenico Coppola, Richard Heller

Bioelectrics Publications

BACKGROUND: Electroporation is an established technique for enhancing plasmid delivery to many tissues in vivo, including the skin. We have previously demonstrated efficient delivery of plasmid DNA to the skin utilizing a custom-built four-plate electrode. The experiments described here further evaluate cutaneous plasmid delivery using in vivo electroporation. Plasmid expression levels are compared to those after liposome mediated delivery.

METHODS: Enhanced electrically-mediated delivery, and less extensively, liposome complexed delivery, of a plasmid encoding the reporter luciferase was tested in rodent skin. Expression kinetics and tissue damage were explored as well as testing in a second rodent model.

RESULTS: Experiments …