BioE Home

BIOE Undergraduate Honors Thesis Defenses 2017

The page below includes defense announcements for Adam Berger,  Timothy HolzbergCasey LimRobert (Reuven) RosenSriramya Ayyagari

Adam Berger

Wednesday, April 12th, 12:30pm
3203 Jeong H. Kim Engineering Bldg

Committee:

Dr. Ian White, Chair
Dr. Peter Kofinas
Dr. Giuliano Scarcelli

Plasmonic Sensors for Detection of Drugs and Small Molecules: Towards Real-World Applications

Surface enhanced Raman spectroscopy (SERS) is a nanotechnology-enabled method of vibrational spectroscopy which has been used for sensitive detection of small molecules, proteins, and nucleic acids. Despite the sensitivity of SERS, it has had limited commercial and translational success due to expense, throughput, and manufacturability issues with current SERS substrates. Designing SERS sensors with an application-based approach is critical to their real-world success. To address this, our lab has pioneered research into paper SERS substrates, as they are cheaper, easier to manufacture, and have inherent fluid flow properties enabling their use as point-of-care diagnostics.

One important potential application of these paper SERS sensors, especially with the push towards precision medicine, is therapeutic drug monitoring (TDM). TDM quantifies the real-time physiological load of an administered drug in order to ensure efficacy and mitigate toxicities. We demonstrate use of inkjet-printed paper SERS substrates for TDM, focusing on effective sample clean-up of a model target drug, flucytosine (5FC), first from serum and then from whole blood using a passive vertical flow scheme. Using this setup, we detect 5FC from human serum at therapeutic levels and in whole blood at the threshold for toxicity.

While the vertical flow scheme provides sufficient detection at clinically relevant concentrations of 5FC, it is unable to provide highly sensitive detection necessary for trace analytes. To address this, we have begun developing a mesoporous, elastic SERS sponge that allows better sample handling. These substrates are fashioned out of polydimethylsiloxane and decorated with nanoparticles. The porous three-dimensional structure simplifies sample acquisition and retains organic solvents, allowing one-step concentration of trace analytes from aqueous samples. The work presented herein rethinks the design of SERS substrates with a focus on real-world diagnostic applications away from the central laboratory.

Timothy Holzberg

Wednesday, April 19th, 9:30am
Kay Boardroom 1 (1107 Jeong H. Kim Engineering Bldg)

Committee:

Dr. John Fisher, Chair
Dr. Gregory Payne
Dr. Steven Jay

Tissue Engineered Cartilaginous Scaffold for Trachea Repair

The trachea is an important part of the respiratory system that connects the larynx to the bronchi, and damage to it can severely impact an individual’s ability to survive. There are currently no clinically viable artificial replacements for this organ, as most fail in vivo due to various issues relating to integration with the existing cartilage tissue. Tissue engineering approaches for developing partial and full trachea models have been investigated, and various design considerations, such as the type of cells used, the material composition, and culture conditions, can impact the clinical success of a scaffold. Our goal is to construct a cartilaginous scaffold that can support cell growth and have the potential for clinical use as a trachea replacement. We have proposed a simple trachea model consisting of a three-dimensional poly(lactic-co-glycolic acid) (PLGA) scaffold seeded with chondrocytes, and we hypothesize that our scaffold will serve as a suitable cartilaginous implant because the material that it is made out of can support cell proliferation and it can be easily fabricated with a patient-specific shape. Extracellular matrix (ECM) formation, chondrocyte viability, and chondrocyte proliferation were evaluated on the first scaffold through immunohistochemistry, live/dead staining, and cell counting with DNA quantification, respectively. Results suggest that our PLGA scaffold constructs can support growth of chondrocytes in vitro, and the cells remained viable during a three week study.

The preliminary success of a single phase cartilaginous scaffold drives us to build a more complex model with more detailed biological functions for a trachea scaffold. We developed a composite model consisting of a 3D printed polycaprolactone (PCL) scaffold seeded with hMSCs and lined with a layer of epithelial cells embedded in gelatin methacrylate (gelMA). We hypothesize that hMSCs will differentiate into cartilage along the surrounding PCL wall in the composite scaffold because the cell composition in the gelMA and PCL closely mimic that of the mucosa and the hyaline cartilage, respectively. Cell viability and chondrogenic differentiation on the second scaffold were assessed with live/dead staining and immunostaining, respectively. We showed that the layer of epithelial cells on the inside of the composite scaffolds did not appear to impact chondrogenic differentiation of hMSCs. These two new artificial trachea scaffolds that can support cell growth in vitro can benefit the clinical treatment of tracheal disease if they are proven to be successful in an in vivo environment.

Casey Lim

Wednesday, April 19th, 11:00am
Kay Boardroom 1 (1107 Jeong H. Kim Engineering Bldg)

Committee:

Dr. John Fisher, Chair
Dr. Helim Aranda-Espinoza
Dr. Kimberly Stroka

3D Printing with DMSO for Carilaginous Scaffolds with Enhanced Bioactivity

Articular cartilage defects are often the result of trauma or prolonged and increasing stress over time affecting individuals over a range of ages. Cartilage has limited self-regenerative ability for critical defects due to lack of proper nutrient supply from blood and lymph vessels. Existing cell based therapies are expensive, time consuming, and difficult to control in terms of cellular response. Alternatively, current acellular based therapies, while less expensive, do not incorporate biological functionalization. In order to achieve more efficient cartilage regeneration, we have developed an acellular 3-D printed bioactive polymer scaffold for treatment of articular cartilage defects. In particular, we have developed a novel printing method using DMSO as a solvent for PLGA, significantly lowering the printing temperature, and allowing for the incorporation of bioactive molecules into the scaffolds. The copolymer poly(lactic-co-glycolic acid) (PLGA) was chosen as the main printing material for the scaffolds, as it is biocompatible, and its mechanical properties can be easily altered to mimic native cartilage mechanical properties. However, printing with PLGA requires too high of a temperature for bioactive molecules to be added. Therefore, we have proposed the use of dimethyl sulfoxide (DMSO), a polar aprotic solvent able to dissolve hydrophilic and hydrophobic molecules, as a solvent to lower the printing temperature of PLGA.

Through this work, we have demonstrated the ability to print refined structures with a PLGA/DMSO complex resin. Mechanical testing has demonstrated PLGA/DMSO scaffolds have similar mechanical properties as native cartilage. Furthermore, after evaporation of DMSO, the scaffolds have confirmed biocompatibility. Additionally, results from biological testing of this printing method with fibronectin have demonstrated the ability to print with bioactive molecules with increased cell adhesion as compared to non-fibronectin printed scaffolds. Moreover, we have established the conditions for printing PLGA/DMSO with transforming growth factor beta3 (TGF-β3). Biological testing of this printing method with TGF-β3 has demonstrated enhanced chondrogenesis, indicating the retained bioactivity of TGF-β3 when printing with DMSO as compared to non-TGF-β3 printed scaffolds. Overall, this work highlights how the use of DMSO as a printing solvent for PLGA will allow for optimal mechanical properties and improved bioactivity of scaffolds for treatment of articular cartilage defects, a quality current printing methodologies have yet to accomplish. Implementation of this approach would improve upon current clinical treatments by providing enhanced biofunctionality to patient specific implantable scaffolds. In the future, this printing technique may expand the incorporation of bioactive molecules into scaffolds to further clinical applications.

Robert (Reuven) Rosen

Thursday, April 20th, 11:00am
Rabin-Barbe Conference Room (2111 Potomac Bldg)

Committee:

Dr. Arthur Johnson, Chair
Dr. Ian White
Dr. Yang Tao

Development of the Airflow Perturbation Device for Respiratory Resistance Control Using Biofeedback Techniques

Studies have shown that the presence of an external monitor of a physiological parameter can enable a subject to obtain cognitive control over the measured parameter and manipulate it at will. This process is known as biofeedback. Biofeedback has been used to treat asthma, anxiety and many other psychological and physiological diseases and ailments. The goal of this project is to explore the benefits of biofeedback on respiratory functionality through monitoring respiratory resistance. Current tools used to measure respiratory resistance are large, expensive, slow, and require trained personnel to operate. A new method to monitor respiratory resistance was developed to explore respiratory resistance control using biofeedback techniques. The new model of the Airflow Perturbation Device, APD2016, allows for a fast and accurate output of respiratory resistance values. The APD2016 differentiates between inhalation and exhalation airway resistances and enables the user to monitor each one individually. It outputs an average respiratory resistance value within three seconds of monitoring the incoming signal and provides an updated moving average value of respiratory resistance up to fifty times a second. This updated value is visually displayed through a needle-gauge display to simplify interpreting the monitored value. This rapid data interpretation and display provides the foundation for biofeedback capabilities and for the development of biofeedback-based respiratory care.

Sriramya Ayyagari

Thursday, April 20th, 2:00 PM
ISR Conference Room (1146 A.V. Williams Bldg)

Committee:
Dr. Steven Jay, Chair
Dr. Kimberly Stroka
Dr. Giuliano Scarcelli

Engineering Proteins for Inducing Vascularization in Chronic Non-Healing Wounds
Chronic non-healing wounds are a serious problem for diabetic patients, where vascular function is impaired. If left untreated, they can lead to other serious complications such as ulcers and infections. Current treatments are limited for chronic wounds and as a result, it is important to look for new therapeutics. This process involves several growth factors that interact with one another in order to stimulate tissue remodeling and vascularization, and may be controlled through activation of particular receptors. Specifically, the ErbB Receptor Family has previously been shown to be important in wound healing. Upon binding Epidermal Growth Factor (EGF), these receptors can undergo dimerization with other ErbB receptors and trigger signaling cascades that result in cell migration and proliferation. However, EGF’s ability to induce a constant cell migratory response is limited. Placental-derived growth factor (PlGF-2) has recently been shown to have a high binding affinity to the ECM and also has been used in fusion proteins with growth factors to induce a prolonged vascularization response. The purpose of this project is to 1) clarify the signaling pathway of the ErbB/EGF pathway in endothelial cells and to design a novel protein with PlGF-2 and EGF in order to target the ErbB receptors, and maximize vascularization response. Preliminary results demonstrate that EGFR homodimers may not be involved in vascularization, and that there may be protein-protein interactions that affect purification of PlGF-2/EGF fusion proteins. Future work aims to determine whether other potential ErbB receptor interactions that can be exploited for therapeutic vascularization.