Biomedical Engineering and Bioengineering Commons^™

Obstacles To Translating The Promise Of Nanoparticles Into Viable Amyloid Disease Therapeutics, N. P. Van Der Munnik, M. A. Moss, M. J. Uline

Faculty Publications

Nanoparticles (NPs) constitute a powerful therapeutic platform with exciting prospects as potential inhibitors of amyloid-β (Aβ) aggregation, a process associated with Alzheimer's disease (AD). Researchers have synthesized and tested a large collection of NPs with disparate sizes, shapes, electrostatic properties and surface ligands that evoke a variety of responses on Aβ aggregation. In spite of a decade of research on the NP-Aβ system and many promising experimental results, NPs have failed to progress to any level of clinical trials for AD. A theoretical framework with which to approach this physical system is presented featuring two simple metrics, (1) the extent …

Diagnostic Performance Of Receptor-Specific Surgical Specimen Staining Correlates With Receptor Expression Level, Jasmin M. Schaefer, Connor W. Barth, Scott C. Davis, Summer L. Gibbs

Dartmouth Scholarship

Intraoperative margin assessment is imperative to cancer cure but is a continued challenge to successful surgery. Breast conserving surgery is a relevant example, where a cosmetically improved outcome is gained over mastectomy, but re-excision is required in >25  %   of cases due to positive or closely involved margins. Clinical translation of margin assessment modalities that must directly contact the patient or required administered contrast agents are time consuming and costly to move from bench to bedside. Tumor resections provide a unique surgical opportunity to deploy margin assessment technologies including contrast agents on the resected tissues, substantially shortening the path to …

Electrical System For Bioelectric Impedance Using Ad5933 Impedance Converter, Allison Garcia, Ahmet C. Sabuncu

SMU Journal of Undergraduate Research

Benchtop lab equipment, such as the HP4194A Precision Impedance Analyzer, offer accuracy and functionality but are often expensive and bulky. Although integrated circuits offer less functionality than benchtop equivalents, they can be a cheaper alternative for smaller applications. In this study, the AD5933 Impedance Converter was investigated as a low-cost option for impedance analysis of the bicep brachii. The AD5933 evaluation board was properly calibrated to measure human muscle by using an equivalent parallel circuit consisting of a 5 nF capacitor and a 1 kOhm resistor. Next, the impedance of the bicep was measured using the AD5933 as the experimental …

Dynamic Light Scattering Optical Coherence Tomography To Probe Motion Of Subcellular Scatterers., Nico J J Arezza, Marjan Razani, Michael C Kolios

Medical Biophysics Publications

Optical coherence tomography (OCT) is used to provide anatomical information of biological systems but can also provide functional information by characterizing the motion of intracellular structures. Dynamic light scattering OCT was performed on intact, control MCF-7 breast cancer cells and cells either treated with paclitaxel to induce apoptosis or deprived of nutrients to induce oncosis. Autocorrelations (ACs) of the temporal fluctuations of OCT intensity signals demonstrate a significant decrease in decorrelation time after 24 h in both the paclitaxel-treated and nutrient-deprived cell groups but no significant differences between the two groups. The acquired ACs were then used as input for …

Raman Spectroscopy As A Predictive Tool For Monitoring Osteoporosis Therapy In A Rat Model Of Postmenopausal Osteoporosis, J. Renwick Beattie, Antonia Sophocleous, M. Clare Caraher, Olive O'Driscoll, Niamh M. Cummins, Steven E.J. Bell, Mark R. Towler, Alireza Rahimnejad Yazdi, Stuart H. Ralston, Aymen I. Idris

Chemical and Biochemical Engineering Faculty Research & Creative Works

Pharmacological therapy of osteoporosis reduces bone loss and risk of fracture in patients. Modulation of bone mineral density cannot explain all effects. Other aspects of bone quality affecting fragility and ways to monitor them need to be better understood. Keratinous tissue acts as surrogate marker for bone protein deterioration caused by oestrogen deficiency in rats. Ovariectomised rats were treated with alendronate (ALN), parathyroid hormone (PTH) or estrogen (E2). MicroCT assessed macro structural changes. Raman spectroscopy assessed biochemical changes. Micro CT confirmed that all treatments prevented ovariectomy-induced macro structural bone loss in rats. PTH induced macro structural changes unrelated to ovariectomy. …

Exploring The Effects Of Electrospun Fiber Surface Nanotopography On Neurite Outgrowth And Branching In Neuron Cultures, Anthony R. D'Amato, Devan L. Puhl, Alexis M. Ziemba, Christopher D.L. Johnson, Janneke Doedee, Jonathan Bao, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

Three aligned, electro spun fiber scaffolds with unique surface features were created from poly-L-lactic acid (PLLA). Fibers without surface nano topography (smooth fibers), fibers with surface divots (shallow pits), and fibers with surface pits (deeper pits) were fabricated, and fiber alignment, diameter, and density were characterized using scanning electron microscopy (SEM). Whole dorsal root ganglia (DRG) were isolated from rats and placed onto uncoated fibers or fibers coated with laminin. On uncoated fibers, neurite outgrowth was restricted by fibers displaying devoted or pitted nano topography when compared to neurite outgrowth on smooth fibers. However, neurites extending from whole DRG cultured …

Quantifying Proliferative And Surface Marker Heterogeneity In Colony‐Founding Connective Tissue Progenitors And Their Progeny Using Time‐Lapse Microscopy, Edward Kwee, Gerald M. Saidel, Kimerly Powell, Christopher M. Heylman, Cynthia A. Boehm, George F. Muschler

Biomedical Engineering

Connective tissue progenitors (CTPs) are defined as the heterogeneous population of tissue‐resident stem and progenitor cells that are capable of proliferating and differentiating into connective tissue phenotypes. The prevalence and variation in clonal progeny of CTPs can be characterized using a colony formation assay. However, colony assays do not directly assess the characteristics of the colony‐founding CTP. We performed large, field‐of‐view, time‐lapse microscopy to manually track colonies back to the founding cells. Image processing and analysis was used to characterize the colonies and their founding cells. We found that the traditional colony‐forming unit (CFU) assay underestimates the number of founding …

Kinematic Foot Types In Youth With Pes Planovalgus Secondary To Cerebral Palsy, Juliet Amene, Joseph J. Krzak, Karen M. Kruger, Logan Killen, Haluk Altiok, Peter A. Smith, Gerald F. Harris

Biomedical Engineering Faculty Research and Publications

Background

Kinematic variability of the foot and ankle segments exists during ambulation among individuals with pes planovalgus (PPV) secondary to cerebral palsy (CP). Clinicians have previously recognized such variability through classification schemes to identify subgroups of individuals, but have been unable to identify kinematic foot types.

Research question

The purpose of this work was to identify kinematic foot types among children with PPV secondary to CP using 3-dimensional multi-segment foot and ankle kinematics during gait as inputs for principal component analysis (PCA) and K-means cluster analysis.

Methods

In a single assessment session, multi-segment foot and ankle kinematics using the …

A Fast, Linear Boltzmann Transport Equation Solver For Computed Tomography Dose Calculation (Acuros Ctd), Adam Wang, Alexander Maslowski, Todd Wareing, Josh Star-Lack, Taly Gilat-Schmidt

Biomedical Engineering Faculty Research and Publications

Purpose

To improve dose reporting of CT scans, patient‐specific organ doses are highly desired. However, estimating the dose distribution in a fast and accurate manner remains challenging, despite advances in Monte Carlo methods. In this work, we present an alternative method that deterministically solves the linear Boltzmann transport equation (LBTE), which governs the behavior of x‐ray photon transport through an object.

Methods

Our deterministic solver for CT dose (Acuros CTD) is based on the same approach used to estimate scatter in projection images of a CT scan (Acuros CTS). A deterministic method is used to compute photon fluence within the …

Novel Supply Chain And Process Modeling For Cell Therapy Manufacturing And Distribution, Chip White, Ben Wang, Kan Wang, Reid Bishop, Aaron Levine, Brian Liu, Bhavya Divvela, Aubrey Incorvaia, Kris Saha, Tava Das

Advancing Manufacture of Cell and Gene Therapies VI [2019]

We present a two-level hierarchical supply chain model of (autologous) CAR-T cell therapy that serves as the basis for the development of strategies to: 1) deliver cell therapy products that are safe and have a high level of efficacy, 2) minimize fulfillment time and variability, and 3) reduce total manufacturing and logistics costs while reducing the risk of patient morbidity and mortality. The model consists of two integral components: (1) an agent-based program for a “single manufacturing facility” that simulates the manufacturing and quality control process of cell therapy; and (2) a supply chain network program that evaluates different supply …

Key Engineering Challenges In The Biomanufacturing Of Lentiviral Viral Vectors, Peter Jones

Advancing Manufacture of Cell and Gene Therapies VI [2019]

No Abstract.

Tangential Flow Filtration And Scalability In Viral Vector Purification, Eni Sterjanaj, Heather Mall, Rachel Legmann, Jacky Dang

Advancing Manufacture of Cell and Gene Therapies VI [2019]

Pall Biotech has linearly scalable tangential flow filtration technology that can cover processing volume ranges from less than a liter to over 2000 liters. Manual assemblies can be used with Pall TFF filters in scales under 20L and programmable skids are available for larger scales. In this document TFF linear scalability of up to 200 liters is covered starting from a 7L initial volume and maintaining similar pressures, processing times and yields at all scales. Using this scalable technology Pall biotech can help biologics companies go to clinical trials and to commercial scale manufacturing successfully.

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Conference Program, Dolores Baksh, Rod Rietze, Ivan Wall

Advancing Manufacture of Cell and Gene Therapies VI [2019]

No abstract provided.

Workshop Agenda, Fernanda Masri

Advancing Manufacture of Cell and Gene Therapies VI [2019]

No abstract provided.

Development Of A Closed Car-T Manufacturing Process, Loo-Yong Steven Kee, Calley Hirsch, Devina Ramsaroop, Elizabeth Csaszar, Danylo Sirskyj, Aaron Dulgar-Tulloch

Advancing Manufacture of Cell and Gene Therapies VI [2019]

The field of immunotherapy has emerged as a promising new type of treatment for cancer with the approval of the first two CAR-T therapies. The clinical success of T-cell based immunotherapies necessitates a robust manufacturing process for these products to be consistently produced at commercial scale. Our CAR-T workflow combines unit operation specific solutions for thaw of an apheresis unit, wash, CD3 selection, T-cell activation, lentiviral transduction, incubator- and reactor-based expansion culture, harvest, formulation, cryopreservation and thaw of CAR-T product. We have evaluated the impact of both serum-containing and xeno-free culture media, commercially available T-cell selection and activation reagents, closed …

Scale-Up Study For Ex-Vivo Expansion Of Allogeneic Natural Killer Cells In Stirred-Tank Bioreactor, Juyoung Kim, Hyung Jin Nam, Sang Hyun Lee, Jong Beom Ku, Seung Ryel Han, Hye Jin Shin, Yu Kyeong Hwang, Sang Hoon Paik

Advancing Manufacture of Cell and Gene Therapies VI [2019]

Natural killer (NK) cells are a type of lymphocyte in the blood that are responsible for innate and adaptive immune response, and they mature in the liver and bone marrow. Being a key role in host defense system with direct and indirect killing of virus-infected cells or cancer cells, NK cell has been considered an attractive candidate for cancer therapy. Peripheral blood shows the low frequency of NK cells, so ex vivo expansion method is important to obtain sufficient NK cells for therapeutic use. Currently, we successfully developed bioreactor process for NK cell expansion on lab-scale. Stirred-tank bioreactor could be …

Single Use Disposable Biosettler Removes The Dead Cells And Cell Debris Selectively To Increase The Viability Percentage Of Mammalian Cells (E.G., Car-T) During Expansion, Dhinakar Kompala

Advancing Manufacture of Cell and Gene Therapies VI [2019]

Current challenge in a FDA approved cell therapy product for adult B-cell leukemia is reported to be the percentage of viable cells after manufacturing is sometimes out of specified range. As the head of a large contract development and manufacturing organization observed, this fall in viability percentage during CAR-T cell manufacturing is a challenge to the whole industry.

We present a simple and powerful off-the-shelf solution to this big challenge in all mammalian cell culture expansion bioreactor system. Our single use disposable BioSettler has been demonstrated to be uniquely capable of removing dead cells and cell debris selectively from the …

Disciplinary Learning From An Authentic Engineering Context, Catherine Langman, Judith Zawojewski, Patricia Mcnicholas, Ali Cinar, Eric Brey, Mustafa Bilgic, Hamidreza Mehdizadeh

Journal of Pre-College Engineering Education Research (J-PEER)

This small-scale design study describes disciplinary learning in mathematical modeling and science from an authentic engineeringthemed module. Current research in tissue engineering served as source material for the module, including science content for readings and a mathematical modeling activity in which students work in small teams to design a model in response to a problem from a client. The design of the module was guided by well-established principles of model-eliciting activities (a special class of problem-solving activities deeply studied in mathematics education) and recently published implementation design principles, which emphasize the portability of model-eliciting activities to many classroom settings.

Two …

The Effect Of Electrospun Fiber Diameter On Astrocyte-Mediated Neurite Guidance And Protection, Christopher D.L. Johnson, Jonathan M. Zuidema, Kathryn R. Kearns, Alianna B. Maguire, Gregory P. Desmond, Deanna M. Thompson, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

The topography of electro spun fiber scaffolds modifies astrocytes toward in vivo-like morphologies and behaviors. However, little is known about how electro spun fiber diameter influences astrocyte behavior. In this work, aligned fibers with two distinct nanoscale fiber diameters (808 and 386 nm) were prepared, and the astrocyte response was measured over time. Astrocytes on the large diameter fibers showed significantly increased elongation as early as 2 h after seeding and remained significantly more elongated for up to 4 days compared to those on small diameter fibers. Astrocytes extending along larger diameter fibers were better equipped to support long neurite …

Coatings On Mammalian Cells: Interfacing Cells With Their Environment, Kara A. Davis, Pei-Jung Wu, Calvin F. Cahall, Cong Li, Anuhya Gottipati, Brad J. Berron

Chemical and Materials Engineering Faculty Publications

The research community is intent on harnessing increasingly complex biological building blocks. At present, cells represent a highly functional component for integration into higher order systems. In this review, we discuss the current application space for cellular coating technologies and emphasize the relationship between the target application and coating design. We also discuss how the cell and the coating interact in common analytical techniques, and where caution must be exercised in the interpretation of results. Finally, we look ahead at emerging application areas that are ideal for innovation in cellular coatings. In all, cellular coatings leverage the machinery unique to …