CRISPR Gene Editing: The Pinnacle of Individualized Medicine
Presenter: Regan Mary Kelly Faculty Sponsor: Reena Randhir School: Springfield Technical Community College Research Area: Biomedical Engineering Location: Poster Session 2, 11:30 AM - 12:15 PM: Campus Center Auditorium [A22]
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), the gene-editing tool has been at the leading-edge of biomedical advancement since its adaption for gene editing in 2012. This study is one of the earliest examples of personalized in vivo CRISPR based therapy. A recent progression in applying CRISPR technology to a human subject has opened the possibility of integrating gene editing tool kits into medical treatment and providing precision-based therapeutic approaches. The research methodology is a review of a published case-study from the New England Journal of Medicine. This powerful and precise gene editing system that can be used to target and modify disease-causing genetic variants within an individual's genome, with the potential to correct underlying genetic disorders rather than only manage symptoms. The subject of this study is an infant diagnosed with a rare Carbamoyl-Phosphate Synthetase 1 Deficiency, a mitochondrial liver enzyme CPS1, that initiates the urea cycle by converting toxic ammonia into a form that can be safely excreted. This disorder is associated with high mortality rate in early infancy. The mechanism of the treatment is a customized lipid nanoparticle- delivered in vivo base editing therapy. Post treatment, the patient was able to receive an increased amount of dietary protein and a reduced dose of a nitrogen-scavenger medication to half of the starting dose. No adverse effects have been observed thus far, though further follow up is warranted to access long-term safety and durability of gene expression. Recent research including the FDA-approved CRISPR-based treatments for inherited blood disorders such as Sickle Cell anemia and clinical trials using systemic delivery platforms further support the clinical potential of this technology. CRISPR-based base editing and targeted delivery systems place gene therapy at the forefront of individualized medicine.
Reading Minds and Controlling Behavior: Elucidating Neural Circuit in the Brain Will Turn Science Fiction Into Reality
Presenter: Ayame Iris Nakagawa Faculty Sponsor: Clarissa Codrington School: Massachusetts Bay Community College Research Area: Biomedical Engineering Location: Poster Session 2, 11:30 AM - 12:15 PM: Campus Center Auditorium [A86]
Can we read someone’s mind and control behavior? This question may sound like something from science fiction and far from reality; however, it may be closer than we expect. All human activities, such as feelings, thoughts, and behaviors, are generated by networks of electrical signaling among neurons in the brain. If we could fully understand these neural activities, it might become possible to interpret our thoughts from outside and even intentionally modify those states by interfering with neural signals.
One potential method for achieving this is brain-computer interface (BCI) technology. Traditionally, BCIs required invasive neurosurgery to implant microelectrode arrays into the brain. However, non-invasive techniques such as functional magnetic resonance imaging (fMRI) have been developed and offer safer alternatives for interpreting brain activity, increasing the possibility of decoding human thoughts and intentions.
Some technologies have been developed to support people with disabilities. Real-time encoding and decoding of brain activity allow speech-impaired patients to communicate without speech or physical movements. Once fully realized, some disabilities may no longer limit patients as they do today. While BCI may bring hope to the medical field there are potential risks, including the erosion of mental privacy, unequal access to cognitive advantages, and the potential undermining of the value of achievements.
This poster will discuss how reading minds and controlling others will be technologically possible, as well as the potential benefits and risks.
The Passive Neuronal Membrane as an RC Circuit
Presenter: Ashley Shepard Faculty Sponsor: Billy Jackson School: North Shore Community College Research Area: Biomedical Engineering Location: Poster Session 2, 11:30 AM - 12:15 PM: Concourse [B12]
A neuron is a cell, mainly located within the central nervous system, that communicates with other cells and transmits information via electrical signals. A direct contribution to the neuron's ability to generate these signals is the composition of its biological structure. Two key components of the neuron's structure, explained within this research, are the cell membrane and the ion channels. Within this research, the comprehensive structure of the neuronal membrane was modelled as a parallel resistor-capacitor circuit using circuit simulation software in an effort to analyze its physiological response to an injected current source in a passive state. The phospholipid bilayer of the neuronal cell membrane stores and separates electric charges, behaving as a capacitor. Meanwhile, the ion channels provide leak pathways that control the ionic flow of current across the cell membrane, acting as a resistor. The possession of resistive and capacitive elements within the neuron's biological structure allow it to be modeled as a resistor-capacitor circuit through the use of specialized circuit simulation software. Within this study, this simulation was performed utilizing PSpice, a commonly used simulation software for electrical circuit modelling. The results of this simulation were then analyzed through the application of classical electromagnetic principles to describe the dynamic behavior of the passive neuronal membrane state. These results provide explanation for membrane voltage responses such as charging and discharging behavior. However, the simple resistor-capacitor circuit model of the passive neuronal membrane captures linear behavior that has several distinct limitations in comparison to more complex nonlinear counterparts.
Targeted Deletion of the gldB Gene to Disrupt Gliding Motility in Cellulophaga lytica
The rod-shaped gram-negative bacteria Cellulophaga Lytica grows in marine ecosystems and has the unique ability of producing iridescence. Iridescence, commonly found in eukaryotes such as birds and fishes, is uncommon to bacteria. C. lytica produces this glitter-like coloration due to the interactions between light and the bacteria’s physical structures arranged in a periodic geometry. Interestingly, the bacteria’s biofilms produce an intense iridescence without a flagella or pili on the cells. Instead, cells depend on gliding motility to transport themselves and form biofilms. Sequencing of C. lytica's genome revealed that the gldB gene, which produces the gld protein, is responsible for the bacteria's gliding motility.
The suicide vector pYT313 is an integrative plasmid that cannot replicate in the target host C. lytica. Its unique design lacks an origin of replication in non-E. coli species, allowing it to replace the target gliding motitlity gene (gldB) with the erythromycin resistance gene (ermF).
In this study, the pYT313 suicide vector is modified to contain the ermF_KO insert such that it can integrate into C. lytica, knockout the gldB gene, and insert erythromycin resistance gene. To do this, we need to modify the pYT313 suicide vector for gene deletion. Golden gate assembly is conducted to ligate the ermF_KO insert into pYT313. Conjugation between modified pYT313 transformed E. coli and C. lytica will allow for direct DNA transfer through a two-step allelic exchange. This will allow us to draw a correlation between the gliding motility of C. lytica and its iridescence through gene deletion
Melanoma continues to pose significant therapeutic challenges, including but not limited to pharmacologic resistance and immune evasion, highlighting the need for delivery systems that enable both precise drug administration and externally tunable therapeutic control. In this work, we report the development of a dual-agent lipid–polymer hybrid nanoparticle platform designed to integrate combinatorial drug delivery with near-infrared (NIR)–responsive modulation. Unlike conventional nanoparticle systems that rely solely on passive delivery, this platform enables externally triggered modulation of therapeutic response through NIR exposure. The nanoparticles were engineered using a poly (lactic-co-glycolic acid) (PLGA) core and a stabilizing lipid shell, providing enhanced formulation robustness and physicochemical uniformity. Particle characterization confirmed a narrow size distribution and a favorable surface charge profile suitable for cellular interaction. The biological performance of the nanoparticle system was evaluated in melanoma stem cell cultures using an alamarBlue viability assay under NIR and non-NIR conditions. The dual-agent nanoparticle formulation produced a reproducible reduction in cell viability relative to control groups, with NIR stimulation further amplifying the observed effect. Together, these findings introduce a modular nanotherapeutic strategy that couples multi-agent delivery with external NIR activation, establishing a flexible framework for melanoma therapy with enhanced control over therapeutic response and future translational optimization.
In the United States, roughly 50 percent of people have used one or more prescription drug in a 30-day period. Despite large demand, conventional drug delivery methods (pills, IV’s, etc.) remain limited by frequent dosing schedules, off-target negative side effects, and gastrointestinal toxicity. To address these limitations, our research proposes an esDLW-printed hollow microneedle array (HMNA), which enables local drug delivery through millimeter long needles that evade pain receptors. Hollow microneedle arrays offer a unique ability to precisely deliver nanoparticles, small molecules, and biologics across the epidermis.
The platform combats burdensome frequent dosing by filling the drug reservoir with a sustained release alginate carrier. Fluorescein and gold nanoparticles (AuNP) were selected as model drugs and were suspended in alginate solutions of various molecular weights. Release studies were first conducted directly into PBS and then through a model of HMNA. For both molecules and under both experimental conditions, drug was proven to diffuse slower from higher molecular weight alginates. This verifies a sustained dosing model for both small molecules and nanoparticles.
This study next seeks to prove that delivery through HMNAs retains the controlled release kinetic pattern. Drug release studies will be repeated in both PBS and an agarose skin mimic, and further experiments will ensure bioactivity of drug passed through HMNA.
Our sustained release HMNA will address limitations of conventional drug delivery methods by painlessly, locally delivering both nanoparticles and small molecules.
Cancer is one of the leading causes of death worldwide. Within tumors exist cancer stem cells (CSCs) capable of differentiation and tumor initiation. A defining characteristic of CSCs is stemness, which is a state of unlimited differential potential and adaptation. Various immune responses can impact CSCs, which can transition between stem-like and differentiated states, complicating immunotherapies. Recent advances in cancer immunotherapies have explored ways to activate the immune system to combat tumors. Innate immune agonists that activate pathways such as Toll-like receptors (TLR) and Stimulator of Interferon Genes (STING) show promise in activating antitumor immunity. To improve delivery and reduce side effects, lipid nanoparticles (LNPs) can be engineered to deliver immune agonists directly to the tumor sites. Co-delivering dual immune agonists (TLR4 and STING) using LNPs has been shown to increase type I interferon responses, leading to improved antigen presentation and activation of T cells. Panc-02 CSCs will be cultured using serum-free media in vitro. Analysis of the CSCs will be done using flow cytometry, where the cells are stained with fluorescent antibodies and an Aldered assay, which measures aldehyde dehydrogenase (ALDH1) to show the stemness potential. This helps assess stemness after the nanoparticle treatment. The efficacy of treatments of CSCs will be measured through fluorescent markers CD24 and CD44, as well as ALDH1 expression. This study can offer a new approach to targeting cancer stem cells to revert stemness and improve antitumor immunity, potentially offering a new therapy for more resistant cancers.
Comparing Machine Learning and Deep Learning Approaches for COPD Exacerbation Risk Assessment
Chronic Obstructive Pulmonary Disease (COPD) is a progressive lung condition that causes breathing difficulties and affects millions worldwide. Acute exacerbations of COPD (AECOPD), a sudden worsening episode requiring emergency care or hospitalization, are a leading driver of patient morbidity and hospital costs, making early risk detection a clinical priority. Inspired by the previous work on the COPDGene cohort, a large dataset containing clinical information from over 10,000 COPD patients, this study investigates whether machine learning (ML) and deep learning (DL) approaches can improve upon earlier classification benchmarks. The input features to the models consist of approximately 300 clinical variables per patient, including demographic information, medical history, and symptom questionnaires. The models are designed to predict exacerbation frequency, classified into seven categories ranging from zero to six or more exacerbations per year. We apply a range of classical machine learning methods, including Support Vector Machines and Gradient Boosted Decision Trees, alongside contemporary deep neural network architectures used to predict patient exacerbation frequency. After identifying the most informative clinical variables, we systematically compare model performance to determine which approaches best capture the relationships between patient characteristics and exacerbation risk. We hypothesize that deep learning architectures will demonstrate improved accuracy in capturing exacerbation risk, owing to their ability to handle more abstract representations of the input data. This work aims to establish updated performance benchmarks and identify promising directions for computational approaches to COPD exacerbation prediction.
Formulation of Smart Hydrogels with Embedded Microparticles for Targeted Melanoma Treatment
Presenter: Emma Thiboutot Faculty Sponsor: Tracie L. Ferreira School: UMass Dartmouth Research Area: Biomedical Engineering Location: Poster Session 4, 2:15 PM - 3:00 PM: Campus Center Auditorium [A77]
This study, “Formulation of Smart Hydrogels with Embedded Microparticles for Targeted Melanoma Treatment,” demonstrates the successful development and characterization of genipin cross-linked PVA-chitosan hydrogels embedded with light-responsive PLGA microparticles for the potential application in localized melanoma therapy. The problem discussed within this proposed project is melanoma skin cancer, with a focus on its impact and the current treatment options available, including chemotherapy, radiation, and surgical interventions, all of which are invasive and often reduce the quality of life. The proposed solution is to develop a novel hydrogel system loaded with PLGA-formulated microparticles that include a mixture of either/and the anti-cancer drug, doxorubicin, or an NIR-responsive dye, indocyanine green, to treat melanoma skin cancer non-invasively with SMART-laser activated drug-releasing hydrogels. The project’s goal is to prove that these hydrogels can effectively target and eliminate melanoma cells with minimal impact on surrounding healthy tissues. Structural analysis via SEM confirmed the presence of pores, with the drug incorporation controlling the distribution, while TGA and DSC revealed that drug loading altered the thermal stability and phase behavior of the hydrogels, and tensile testing confirmed that the mechanical integrity was retained after cross-linking. Swelling studies conducted in ultra-pure water, PBS, and DMEM highlighted altered swelling capacity due to drug and polymer interactions. Importantly, the AlamarBlue assays confirmed the biocompatibility of PVA-chitosan alone, while DOX and ICG-loaded formulations, especially the samples exposed to NIR, showed significant cytotoxicity toward melanoma cells, demonstrating enhanced photothermal or chemotherapeutic impact and supporting therapeutic potential.
OMNI: An Osmotic MicroNeedle Implant Towards Long-term Direct-to-Brain Drug Delivery
Delivering drugs directly to the brain is a major medical challenge due to the blood-brain barrier (BBB). The olfactory pathway, which connects the nasal cavity to the brain, offers a promising route to bypass this barrier, but current methods lack the sustained, controlled release needed for long-term treatment. To address this, we developed the Osmotic MicroNeedle Implant (OMNI), a miniature, power-free device designed for extended implantation.
OMNI is a first-of-its-kind device fabricated entirely using multi-material 3D Direct Laser Writing. It integrates two key components: a soft osmotic chamber with a semi-permeable membrane, and a drug reservoir connected to a hollow microneedle array. After implantation in the olfactory submucosa, the device uses the body’s own interstitial fluid as a power source. Fluid enters the osmotic chamber, causing an osmotic agent to expand. This expansion pressurizes the reservoir, driving the drug through the microneedles and directly into the tissue.
We validated the device in vitro. Accelerated testing showed that the osmotic engine activates upon fluid contact, generating sustained pressure. In a tissue-mimicking gel, the fully assembled OMNI successfully expelled a drug surrogate and delivered it locally without any external power. This work establishes the feasibility of a fully additive manufactured, implantable osmotic pump for the CNS. By enabling long-term, controlled, and targeted drug delivery, OMNI offers a potential new strategy for treating chronic neurological conditions.
Optimizing Ultrasonication Parameters for the Delivery of Graphene-Based Nano E-Tattoos in Continuous Health Monitoring
Continuous and non-invasive health monitoring is essential for managing chronic diseases, yet existing wearable sensors often lack the biocompatibility and longevity required for everyday use. This study investigates the development of graphene-based nano e-tattoos which are ultra-thin, conductive sensors designed to monitor physiological signals for up to ten days. Despite the potential of these devices, a significant challenge remains in achieving a reproducible and safe delivery method that ensures consistent electrical performance without damaging biological tissue. The research employs a mixed-methods experimental approach to optimize an ultrasonication-based delivery system. By embedding conductive nanomaterials into a biocompatible polymer matrix of sodium alginate and chitosan, the study investigates how variables such as probe geometry (2 mm vs. 12 mm), pulse cycles, and probe-to-skin distance influence ink penetration and signal retention. Quantitative data was gathered through resistance and impedance measurements, while qualitative histological analysis was used to assess skin integrity and cytotoxicity. The study’s hypotheses suggest that transitioning from manual probe application to a standardized, stationary pulse-mode method can significantly reduce human error and improve electrical conductivity. Preliminary results indicate that while closer probe proximity (1 mm) minimizes electrical resistance, it increases the risk of thermal buildup. Conversely, a 3 mm distance between the probe and skin provides superior structural definition and reproducibility. This research offers a deeper understanding of the mechanical-biological interface, providing a framework for public health technology to move toward more resilient, patient-friendly monitoring systems. By optimizing these delivery parameters, researchers can create more effective tools for early disease detection in an evolving healthcare landscape.
Role of Nicotine on Bone Metabolism Using DBP-Based Organoids
Presenter: Daniel Jungwoo Kim Faculty Sponsor: Jungwoo Lee School: UMass Amherst Research Area: Biomedical Engineering Location: Poster Session 5, 3:15 PM - 4:00 PM: Room 165 [D9]
Nicotine is a chemical compound widely used for leisure, most commonly through cigarette smoking, but also distributed in the form of nicotine patches, gums, and e-cigarettes for smoking cessation. Its impact on bone health, however, remains controversial and not fully understood. Clinical studies have reported that smokers exhibit lower bone mineral density and increased risk of osteoporosis and fracture, but it remains unclear whether these outcomes arise from nicotine itself or from other components of tobacco smoke. In vitro studies have reported both stimulatory and inhibitory effects of nicotine on osteoblast proliferation, differentiation, and mineralization, depending on concentration and exposure duration. These conflicting findings highlight the need for controlled experimental models to explain the concentration-dependent and receptor-mediated effects of nicotine on bone cells. This project aims to elucidate the role of nicotine in bone metabolism using DBP-based bone organoids that recapitulate key structural and functional features of native bone tissue. By leveraging this three-dimensional organoid platform, this experiment will show how nicotine exposure modulates osteoblast activity, mineral deposition, osteoclast differentiation, and overall bone remodeling dynamics. This experiment will focus on the relationship between nicotine and nicotinic acetylcholine receptors (nAChRs) to understand the exact signaling mechanism by which nicotine affects bone-regulating cells and processes. Through this approach, the study will provide mechanistic insight into nicotine’s role in skeletal pathology and inform public health considerations for populations exposed to nicotine through both recreational and therapeutic delivery systems.
Effects of Asymmetric Surface Stiffness Walking on Lower Limb Muscle Activity
Presenter: Lauren E. Baranowski Faculty Sponsor: Meghan Huber School: UMass Amherst Research Area: Biomedical Engineering Location: Poster Session 6, 4:15 PM - 5:00 PM: Campus Center Auditorium [A12]
INTRODUCTION: Stroke is a long-term adult disability, with 80% of stroke survivors experiencing gait impairments. Interventions that manipulate walking conditions, such as Asymmetric surface stiffness walking have shown to induce neuromotor adaptation and improve gait symmetry. However, these adaptations have previously been assessed through treadmill-based aftereffects, which may not accurately reflect functional overground gait. Additionally, most work has focused on weight-bearing symmetry rather than neuromuscular response. Therefore, this study evaluated the transfer of aftereffects in lower limb muscle activity from symmetric surface stiffness treadmill walking to overground walking.
METHODS: 5 healthy individuals completed a speed test trial on a 12.5m overground walkway to determine their preferred walking speed. Participants then completed three baseline walking trials on the same walkway. Next, participants walked for 12-minutes on an adjustable surface stiffness treadmill (AdjuSST), with a 2-minute acclimation period followed by a 10-minute adaptation period. During adaptation, one leg walked on a rigid belt (300 kN/m) while the contralateral leg walked on a compliant belt (15 kN/). After effects were assessed during a 5-minute post-condition while participants walked overground.
RESULTS: During adaptation, changes in muscle activation were observed between the limbs relative to baseline walking. By late adaptation, participants demonstrated changes in gait symmetry consistent with neuromotor adaptation. During the post condition, alterations in lower limb muscle activity persisted as participants transitioned to overground walking.
CONCLUSIONS: These results indicate that asymmetric stiffness surface walking produced aftereffects in lower limb muscle activation that transferred to overground walking. Further research is needed to evaluate whether these adaptations persist following repeated interventions.
Systematic Screening of Lipid Nanoparticles Surface Properties for Diffusion and Retention in the Brain
Presenter: Vy Do Faculty Sponsor: Jingjing Gao School: UMass Amherst Research Area: Biomedical Engineering Location: Poster Session 6, 4:15 PM - 5:00 PM: Campus Center Auditorium [A33]
Genetic medicine offers tremendous advantages for the treatment of various central nervous system (CNS) diseases by modulating root-cause mechanisms through gene expression regulation. Lipid nanoparticles (LNPs) have been widely employed as delivery vectors for gene therapy due to their low immunogenicity, protection against cargo degradation, and high tunability. While LNPs for brain delivery have been mostly engineered to bypass the blood-brain barrier (BBB), the spatial distribution and cellular tropism of LNPs within the brain parenchyma are also critical factors in determining their translational success. However, how surface physicochemical properties govern interactions between LNPs and the brain environment to determine their residence is poorly understood. In this study, we formulated 65 LNPs with varying surface functional lipids and concentrations and injected them into hippocampal or cortical sites to evaluate their diffusion, retention, and cell-type specificity. Through parallel high-throughput screening, we identified top-performing formulations with distinct spreading and localization capabilities and validated their performance by delivering eGFP mRNA. Our results reveal a panel of LNP formulations with diffusion or retention profiles across brain regions and their preferential uptake by specific brain cell types, allowing for applications in targeted delivery to specific areas or cell populations relevant to neurodegenerative diseases. This study establishes a foundation for further rational development of LNPs with engineered surface characteristics for targeted CNS gene delivery.
It is estimated that 50 million people worldwide live with neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s. Gene therapies can help slow or reverse their progression. However, delivering them to the brain is difficult because of the blood-brain barrier (BBB). The BBB is made up of brain endothelial cells and other glial cells that regulate selective permeability of molecules and ions from the blood into the brain. This prevents large drugs and their carriers from crossing into brain tissue.
Lipid Nanoparticles (LNPs) are promising candidates for delivering gene therapies. They are biocompatible, nano-sized spherical drug carriers made of specialized phospholipids and cholesterol encapsulating genetic cargo. They also mimic lipoproteins, which are spherical carriers of triglycerides and cholesterol in the body’s natural lipid delivery system.
Lipoproteins display various proteins on their surface that promote cell adhesion and uptake into cells, including brain endothelial cells. These proteins can be adsorbed onto the surface of LNPs by incubation, allowing them to mimic lipoprotein properties for cell adhesion and endocytosis.
In this study, I will make LNPs and incubate them with various concentrations of each protein of interest. Protein adsorption will be quantified using Western blotting and ELISA. The functionalized LNPs will be tested on brain endothelial cells in transwell assays to determine cell adhesion and gene therapy delivery efficiency compared to controls. The results of this study will help evaluate LNPs as an effective delivery platform for gene therapy medications to treat CNS disorders.
Intubation Aid for Pregnant Patients
Presenter: Kayla Gitonga Faculty Sponsor: Cathal J. Kearney School: UMass Amherst Research Area: Biomedical Engineering Location: Poster Session 6, 4:15 PM - 5:00 PM: Campus Center Auditorium [A46]
Anatomical and physiological changes during pregnancy, including increased airway edema, significantly complicate airway management during procedures such as cesarean sections. These changes result in intubation failure rates that are two to three times higher than in non-pregnant patients, along with higher risk of airway trauma, aspiration, and maternal morbidity. Intubation of pregnant patients is advised against as current airway devices are not suitable to safely manage their airway. This design proposes a de-edema spray device with the purpose of reducing swelling of the airway during the pre-operative phase of planned procedures. The device delivers medication through a flexible transnasal wand during the pre-oxygenation window, allowing for edema reduction prior to intubation. This device uses a spring-actuated pump within the ergonomic handle composed of clinically compatible and manufacturable materials. Regulatory guidelines for risk management, biocompatibility, and safety informed the design process to ensure safe and reliable intranasal use in patients. Design specifications were advised by user needs including clinical performance, safety, and manufacturability with defined marginal and ideal targets. A PLA prototype of the handle and internal spray mechanism will undergo verification and validation testing, including repeated- use durability assessments, spray particle size analysis, and user-handling simulations to confirm alignment with design specifications. By addressing airway edema prior to intubation, this device aims to improve airway management through targeted medication delivery that reduces swelling, facilitates safer intubation, and enhances maternal safety in high-risk patients.
The Influence of Mechanically Stimulated Osteocytes on Metastatic Breast Cancer Cell Behavior
Breast cancer is a deadly disease impacting millions of women worldwide and, when metastasized to bone, further decreases quality of life and life expectancy for patients. Osteocytes, the most abundant bone cell, respond to mechanical cues to regulate bone remodeling and control pathways that influence tumor cell invasion. However, there is limited knowledge on how mechanically stimulated osteocytes affect cancer cell behavior and metastasis. It is hypothesized that mechanical stimulation will cause osteocytes to secrete cytokines that promote cancer cell proliferation, creating a pro-metastatic environment. Breast cancer cells are also expected to alter osteocyte signaling, causing them to shift bone remodeling dynamics to support the “vicious cycle” of metastasis that causes osteolytic tumors. The major aims of this project are to: (1) evaluate the effects of mechanically stimulated osteocytes on breast cancer cell behavior and (2) determine whether breast cancer cells directly interact with osteocytes and modulate their signaling pathways. OCY-454 cells were subjected to fluid shear stress on an orbital shaker, simulating the mechanical loading that osteocytes experience physiologically. The conditioned media was used to culture PY8119 and behavior characterization was performed. CCK8 assay showed increased cancer cell proliferation, while ICC revealed morphology changes in treated OCY-454 and PY8119 cells. Ongoing work includes a direct co-culture between PY8119 and OCY-454 cells; qPCR will quantify changes in osteocyte gene expression, expecting an increase in mechanosensitive and resorptive genes. Results will provide greater understanding of interactions between osteocytes and cancer cells, informing the mechanisms behind bone metastasis.
Modulation of Endothelial Permeability with Pulsed Electric Fields for Targeted Drug Delivery
Pulsed electric fields (PEF) are known to affect the cytoskeleton of epithelial and endothelial cells, triggering actin remodeling and the internalization of gap junctions. I hypothesized that such changes in cells within the endothelial layer would disrupt barrier function, increasing the transport of molecules. A microphysiological system (MPS) representing an arteriole was built to test this hypothesis. A screening experiment was performed to assess the relationship between PEF energy dose and the severity of changes in barrier function in endothelial layers using the MPS chip. Permeability trackers 10kDa FITC Dextran (FITC) and 70kDa Rhodamine Dextran (Rhod) were used to capture the kinetics of barrier function change and transport across the layer. Treating with chips with PEF at 25 bursts using a moderate field strength of 500 v/cm showed a 41.6% increase in the diffusion of FITC and a 30.5% increase in Rhod diffusion. Increasing the field strength to 1000 v/cm showed an 84.8% increase in FITC transport and a 71.9% increase in Rhod transport through the vessel. The data for FITC, as compared to the Rhod, showed more movement through the vessel wall since smaller molecules experience less difficulty in diffusion. Using MPS, I have shown that a temporary increase in vessel permeability can be achieved using PEF without destroying vessel wall integrity long-term. The results show that this technique could be used for direct delivery of drugs to specific sites in the body.
Biofilm Formation and Quorum Sensing in 2D vs 3D Microenvironments
Presenter: Erin Kim Faculty Sponsor: Sang Hyun Lee School: UMass Amherst Research Area: Biomedical Engineering Location: Poster Session 6, 4:15 PM - 5:00 PM: Room 163 [C18]
Biofilm in porous environments plays an important role in
ecological and biomedical systems, yet conventional microfluidic platforms
often rely on simple two-dimensional (2D) channel geometries that do not
capture the structural complexity and flow tortuosity of natural porous media.
To address this limitation, I developed microfluidic chips incorporating both
2D patterned cylinders (1000 μm × 500 μm x 500 μm) and three-dimensional (3D)
architectures composed of repeating hemispherical features (1000 μm × 500 μm × 500
μm) fabricated using a biocompatible 3D‑printing resin. The goal of this
work was to compare biofilm formation and quorum sensing (QS), which regulates
biofilm formation, signal dynamics under geometrically distinct
microenvironments.
Green fluorescence protein (GFP)-tagged Pseudomonas
aeruginosa, a clinically relevant QS-active strain known to form biofilms
through C4-HSL and 3-oxo-C12-HSL N‑acylhomoserine lactones (AHLs) QS
signal molecules was chosen as our model bacterium and injected via a syringe
pump at a fixed rate. Extracellular QS signal levels were quantified using the
AHLs-responsive reporter strain Agrobacterium tumefaciens A136 (Ti−)(pCF218)(pCF372), which expresses β-galactosidase
upon detecting a broad range of AHLs. Biofilm formation and spatial distribution
was then quantified and compared in 2D and 3D geometries. In addition, flow
simulations were conducted to assess the velocity field and shear stress in the
considered structures by solving Navier-Stokes equation in COMSOL.
Through this work, I aim to highlight the importance of
microenvironmental architecture in shaping biofilm proliferation and QS
activity. The developed 3D patterned microchip provides a more realistic
platform for studying biofilm behavior and may support future investigations
into suppressing biofilm growth.