Biomedical Engineering and Bioengineering Commons^™

Extracellular-Vesicle-Based Therapeutics In Neuro-Ophthalmic Disorders, Hamed Massoumi, Sohil Amin, Mohammad Soleimani, Bita Momenaei, Mohammad Javad Ashraf, Victor H Guaiquil, Peiman Hematti, Mark I Rosenblatt, Ali R Djalilian, Elmira Jalilian

Wills Eye Hospital Papers

Extracellular vesicles (EVs) have been recognized as promising candidates for developing novel therapeutics for a wide range of pathologies, including ocular disorders, due to their ability to deliver a diverse array of bioactive molecules, including proteins, lipids, and nucleic acids, to recipient cells. Recent studies have shown that EVs derived from various cell types, including mesenchymal stromal cells (MSCs), retinal pigment epithelium cells, and endothelial cells, have therapeutic potential in ocular disorders, such as corneal injury and diabetic retinopathy. EVs exert their effects through various mechanisms, including promoting cell survival, reducing inflammation, and inducing tissue regeneration. Furthermore, EVs have shown …

Multiple And Consecutive Genome Editing Using I-Gonad And Breeding Enrichment Facilitates The Production Of Genetically Modified Mice, Carolina R Melo-Silva, Cory J Knudson, Lingjuan Tang, Samita Kafle, Lauren E. Springer, Jihae Choi, Christopher M. Snyder, Yajing Wang, Sangwon V. Kim, Luis J. Sigal

Department of Microbiology and Immunology Faculty Papers

Genetically modified (GM) mice are essential tools in biomedical research. Traditional methods for generating GM mice are expensive and require specialized personnel and equipment. The use of clustered regularly interspaced short palindromic repeats (CRISPR) coupled with improved-Genome editing via Oviductal Nucleic Acids Delivery (i-GONAD) has highly increased the feasibility of producing GM mice in research laboratories. However, genetic modification in inbred mouse strains of interest such as C57BL/6 (B6) is still challenging because of their low fertility and embryo fragility. We have successfully generated multiple novel GM mouse strains in the B6 background while attempting to optimize i-GONAD. We found …

Identification Of Proteins Involved In Cell Membrane Permeabilization By Nanosecond Electric Pulses (Nsep), Giedre Silkuniene, Uma Mangalanathan, Alessandra Rossi, Peter A. Mollica, Andrei G. Pakhomov, Olga N. Pakhomova

Bioelectrics Publications

The study was aimed at identifying endogenous proteins which assist or impede the permeabilized state in the cell membrane disrupted by nsEP (20 or 40 pulses, 300 ns width, 7 kV/cm). We employed a LentiArray CRISPR library to generate knockouts (KOs) of 316 genes encoding for membrane proteins in U937 human monocytes stably expressing Cas9 nuclease. The extent of membrane permeabilization by nsEP was measured by the uptake of Yo-Pro-1 (YP) dye and compared to sham-exposed KOs and control cells transduced with a non-targeting (scrambled) gRNA. Only two KOs, for SCNN1A and CLCA1 genes, showed a statistically significant reduction in …

Objectively Measuring Effects Of Electro-Acupuncture In Parkinsonian Rhesus Monkeys, Rui Zhang, Anders H. Andersen, Peter A. Hardy, Eric Forman, April Evans, Yi Ai, Jin Yue, Guihua Yue, Don M. Gash, Richard Grondin, Zhiming Zhang

Magnetic Resonance Imaging and Spectroscopy Center Faculty Publications

Acupuncture has increasingly been used as an alternative therapy for treatment of Parkinson’s disease (PD). However, the efficacy of acupunture for PD still remains unclear. The present study was designed to objectively and safely monitor anti-parkinsonian effects of electroacupuncture (EA) and brain activity in nonhuman primates modeling human PD. Six middle-aged rhesus monkeys were extensively studied by a computerized behavioral testing battery and by pharmacological MRI (phMRI) scans with specific dopaminergic drug stimulations. All animals were evaluated for behavior and phMRI responses under normal, parkinsonian, parkinsonian with EA treatment and parkinsonian after EA treatment conditions. Stable parkinsonian features were observed …

Computational Sensitivity Investigation Of Hydrogel Injection Characteristics For Myocardial Support, Hua Wang, Christopher B. Rodell, Madonna E. Lee, Neville N. Dusaj, Joseph H. Gorman Iii, Jason A. Burdick, Robert C. Gorman, Jonathan F. Wenk

Mechanical Engineering Faculty Publications

Biomaterial injection is a potential new therapy for augmenting ventricular mechanics after myocardial infarction (MI). Recent in vivo studies have demonstrated that hydrogel injections can mitigate the adverse remodeling due to MI. More importantly, the material properties of these injections influence the efficacy of the therapy. The goal of the current study is to explore the interrelated effects of injection stiffness and injection volume on diastolic ventricular wall stress and thickness. To achieve this, finite element models were constructed with different hydrogel injection volumes (150 µL and 300 µL), where the modulus was assessed over a range of 0.1 kPa …

An Imaging-Based Platform For High-Content, Quantitative Evaluation Of Therapeutic Response In 3d Tumour Models, Jonathan P. Celli, Imran Rizvi, Adam R. Blanden, Iqbal Massodi, Iqbal Massodi, Michael D. Glidden, Brian Pogue, Tayyaba Hasan

Dartmouth Scholarship

While it is increasingly recognized that three-dimensional (3D) cell culture models recapitulate drug responses of human cancers with more fidelity than monolayer cultures, a lack of quantitative analysis methods limit their implementation for reliable and routine assessment of emerging therapies. Here, we introduce an approach based on computational analysis of fluorescence image data to provide high-content readouts of dose-dependent cytotoxicity, growth inhibition, treatment-induced architectural changes and size-dependent response in 3D tumour models. We demonstrate this approach in adherent 3D ovarian and pancreatic multiwell extracellular matrix tumour overlays subjected to a panel of clinically relevant cytotoxic modalities and appropriately designed controls …

Quantitative, Spectrally-Resolved Intraoperative Fluorescence Imaging, Pablo A. Valdés, Frederic Leblond, Valerie L. Jacobs, Brian C. Wilson, Keith D. Paulsen, David W. Roberts

Dartmouth Scholarship

Intraoperative visual fluorescence imaging (vFI) has emerged as a promising aid to surgical guidance, but does not fully exploit the potential of the fluorescent agents that are currently available. Here, we introduce a quantitative fluorescence imaging (qFI) approach that converts spectrally-resolved data into images of absolute fluorophore concentration pixel-by-pixel across the surgical field of view (FOV). The resulting estimates are linear, accurate, and precise relative to true values, and spectral decomposition of multiple fluorophores is also achieved. Experiments with protoporphyrin IX in a glioma rodent model demonstrate in vivo quantitative and spectrally-resolved fluorescence imaging of infiltrating tumor margins for the …

Resting-State Connectivity Identifies Distinct Functional Networks In Macaque Cingulate Cortex., R Matthew Hutchison, Thilo Womelsdorf, Joseph S Gati, L Stan Leung, Ravi S Menon, Stefan Everling

Physiology and Pharmacology Publications

Subregions of the cingulate cortex represent prominent intersections in the structural networks of the primate brain. The relevance of the cingulate to the structure and dynamics of large-scale networks ultimately requires a link to functional connectivity. Here, we map fine-grained functional connectivity across the complete extent of the macaque (Macaca fascicularis) cingulate cortex and delineate subdivisions pertaining to distinct identifiable networks. In particular, we identified 4 primary networks representing the functional spectrum of the cingulate: somatomotor, attention-orienting, executive, and limbic. The cingulate nodes of these networks originated from separable subfields along the rostral-to-caudal axis and were characterized by positive and …

Quantitative Cherenkov Emission Spectroscopy For Tissue Oxygenation Assessment, Johan Axelsson, Adam K. Glaser, David J. Gladstone, Brian W. Pogue

Dartmouth Scholarship

Measurements of Cherenkov emission in tissue during radiation therapy are shown to enable estimation of hemoglobin oxygen saturation non-invasively, through spectral fitting of the spontaneous emissions from the treated tissue. Tissue oxygenation plays a critical role in the efficacy of radiation therapy to kill tumor tissue. Yet in-vivo measurement of this has remained elusive in routine use because of the complexity of oxygen measurement techniques. There is a spectrally broad emission of Cherenkov light that is induced during the time of irradiation, and as this travels through tissue from the point of the radiation deposition, the tissue absorption and scatter …

Organization And Signal Processing Of The Descending Tracts In The Cervical Spinal Cord, Yanmei Tie

Doctoral Dissertations

This dissertation addresses the research for the development of spinal cord-computer interface (SCCI). The main objective of SCCI is to generate voluntary motor control signals for individuals with spinal cord injury (SCI).

In the neuroscience aspect, organization of the fibers in the descending tracts of the dorsolateral funiculus of the cervical spinal cord was investigated in cats. The spinal cord was penetrated with silicon substrate microelectrodes at 400 μm intervals in the medio-lateral direction at the C5/C6 and C6/C7 segmental borders. The stimulus consisted of a 20 ms train of charge-balanced biphasic pulses at 330 Hz. The evoked activities from …