Molecular, Cellular, and Tissue Engineering Commons^™

The Effects Of Low-Frequency, Low-Intensity Ultrasound On Gene Expression In Macrophage-Endothelial Cell Co-Culture, Evelyn Hergenhan

Honors Theses

Introduction

Low-frequency, low-intensity ultrasound (LFLI US) has been shown to be a promising treatment for noninvasive accelerated chronic wound healing. However, the biological mechanisms of this ultrasound-assisted healing are not yet understood, limiting clinical adoption. The objective of this study is to characterize the effects of LFLI US on gene expression in a simulated chronic wound environment to gain a better understanding of the biological mechanisms underlying this therapeutic.

Methods

A simulated chronic wound environment consisting of endothelial cells and inflammatory M1 macrophages co-cultured in 3D was subject to LFLI US at 50, 100, or 150 mW/cm² Spatial-Peak, Temporal-Peak …

Stentrx, Emma Barna, Minuthi Cooray, Bruce Newlands, Joseph A. Sabetta

Williams Honors College, Honors Research Projects

This project aims to develop a biodegradable, drug-eluting biliary stent for the treatment of biliary cancers. Current metal stents that restore bile flow bit are non-degradable, prone to migration, and unable to deliver drugs locally. The proposed stent will be biocompatible, biodegradable, and capable of controlled drug release to both maintain bile flow and treat tumors. The end goal is to produce a functional prototype that can be deployed via a minimally invasive catheter and maintain bile duct patency for at least three months. The project is expected to be involved in the NEOMED Bench-to-Bedside competition and provisionally patented.

Yk-4-250, A Synthetic Telmisartan-Tempol Conjugate: Crystal Structure Of A Stabilized Free Radical Containing An Angiotensin At₁ Receptor Inhibitor, Simon Friedrich, Yali Kong, Faik N. Musayev, Milton L. Brown, B. Frank Gupton

Department of Biomedical and Translational Sciences Faculty Publications

We report the first crystal structure of the telmisartan-tempol conjugate 2,2,6,6-tetramethyl-1-(λ'-oxidaneyl)piperidin-4-yl 4'-[(1,7'-dimethyl-2'-propyl-1H,3'H-[2,5'-bibenzo[d]imidazol]-3'-yl)methyl]-[1,1'-biphenyl]-2-carboxylate free radical (YK-4-250, C₄₂H₄₆N₅O₃), a dual-function inhibitor designed to target both the angiotensin II type 1 receptor (AT₁R) and reactive oxygen species (ROS). Structural analysis reveals a unique crystal architecture in which the nitroxide radical is stabilized within a sterically protected environment while preserving the telmisartan pharmacophore essential for high-affinity receptor antagonism. YK-4-250 is a novel small-molecule conjugate of telmisartan and tempol that incorporates a catalytic stabilized nitroxide radical and was rationally designed to mitigate gastrointestinal acute radiation syndrome (GI-ARS).

Establishment And Histopathological Characterization Of A Kyse-30 Subcutaneous Xenograft Model Of Esophageal Squamous Cell Carcinoma, Pavel A. Solopov, Alayna Enos, Mantas Silkunas, Giedre Silkuniene, Eleni Zivla, Andrei G. Pakhomov, Olga N. Pakhomova

Bioelectrics Publications

Background/Objectives: Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with poor prognosis and limited treatment options, highlighting the need for reliable preclinical models for translational research. Although xenograft models are widely used in cancer biology, systematic characterization of subcutaneous ESCC models under defined implantation conditions remains limited. The objective of this study was to systematically compare implantation conditions and define histopathological and growth-related parameters that enable reproducible tumor establishment while maintaining a practical experimental window for therapeutic studies. Methods: We established and characterized a subcutaneous ESCC xenograft model using human ESCC cell line KYSE-30 implanted into immunodeficient J:NU mice. …

Bioprinted Scaffolds For Investigating Fibroblast Alignment, Lillian Thro, Daeha Joung Ph.D.

Undergraduate Research Posters

Fibroblasts play a vital role in tissue repair, ECM remodeling, and maintaining structural integrity in human tissues. However, their behavior in engineered 3D microenvironments remains poorly understood. Traditional 2D cultures fail to capture the complex cell-cell and cell-matrix interactions that govern fibroblast alignment, migration, and proliferation in vivo. To address this gap, this project uses bioprinted scaffolds that mimic native ECM structures and provide a platform for studying fibroblast behavior in controlled microenvironments. The project focuses on varying scaffold channel properties—such as width, depth, and geometry—to investigate how physical cues influence fibroblast organization and collective migration. A biodegradable gelatin-based ECM …

Injectable Hydrogels For Bone Regeneration: Mechanical Reinforcement Strategies Using Nanoparticles And Nanofibers: Review Paper, Fariba Ganji, Morteza Mirzagoli, Lobat Tayebi

Electrical & Computer Engineering Faculty Publications

Background and Purpose: The growing demand for bone regeneration following severe injuries highlights the importance of scaffolds in bone tissue engineering (BTE). Injectable hydrogels have emerged as promising candidates because their properties closely mimic the native extracellular matrix (ECM). However, their limited mechanical strength and structural instability restrict their practical application. Approach: This review summarizes recent strategies for reinforcing in situ-forming injectable hydrogels to improve their mechanical performance for bone regeneration. Particular emphasis is placed on nanomaterial-based strategies, including the incorporation of nanoparticles and nanofibers, and their ability to enhance the physical properties of polymeric networks. Key Results: Evidence from …

Design And Validation Of A Novel Patterned Microfluidic Culture Platform For Hipsc-Cm Maturation, Anisia Gabriela Țiplea

Dartmouth College Master’s Theses

Adult cardiomyocytes (CMs) are among the most challenging cells to culture in vitro, given their poor adherence to plastic culture wells and poor maturation outside the native extracellular matrix (Narkar et al., 2022). Human induced pluripotent stem cell-derived CMs (hiPSC-CMs) offer a viable alternative to study heart development and disease progression. While not comparable to adult CMs in their maturity (Narkar et al., 2022), they mimic the clinical phenotypes of heart failure and are more feasible to culture. Nevertheless, hiPSC-CMs require specialized culture conditions that cannot be achieved with 2D static culturing, which fail to replicate native tissue environments (X. …

Forcing A Molecule To Switch: Quantifying Mechanical Control At The Atomic Scale, A. M. Shashika D. Wijerathna, Markus Zirnheld, Michael L. Hildebrand, Myles Perry, Marjorie Cenese, Yuan Zhang

Physics Faculty Publications

Mechanically induced conformational switching at the single-molecule level represents a fundamental mechanism for molecular functionality, yet quantitative characterization of the underlying force and energy landscape remains limited. Here, we study individual TBrPP-Co(II) molecules on Au(111) using qPlus atomic force microscopy. By reconstructing interaction potentials from 3D Δf(x,y,z) data, we determine a threshold force of ∼96 ± 8 pN and a tip-induced switching interaction energy of ∼38 ± 4 meV associate with the conformational transition. The isolated tip-molecule force follows a power law (exponent ∼6), indicating dominance of long-range van der Waals interactions. …

Synthesis And Characterization Of Glass-Ceramic Nanoparticles And Nanobubbles For Integration Into Bone Regenerative Biomaterials, Sun Latt

Honors Undergraduate Theses

Osteoporosis affects over 200 million individuals worldwide and is characterized by an imbalance between osteoclastic bone resorption and osteoblastic bone formation, leading to fragility fractures that significantly diminish quality of life. Current clinical bone cements, such as poly(methyl methacrylate), are limited by poor osseointegration, toxic monomers, and an inability to address the underlying pathophysiology of osteoporosis. This work presents the synthesis, characterization, and systematic in vitro evaluation of a sol-gel-derived, magnesium-incorporated glass-ceramic (GC) nanoparticle within the CaO-MgO-SiO₂ system for incorporation into a novel hydrogel bone cement and bioresorbable magnesium implants. XRD confirmed a biphasic amorphous-crystalline diopside composition, and TEM …

Circulating Biomarker Results From A Phase 2 Study Of Seralutinib In Pulmonary Arterial Hypertension, Robin Osterhout, Athénaïs Boucly, Raymond L. Benza, Richard N. Channick, Kelly M. Chin, Robert P. Frantz, Anna R. Hemnes, Luke S. Howard, Vallerie V. Mclaughlin, Olivier Sitbon, Jean-Luc Vachiéry, Rotham T. Zamanian, Richard Aranda, Matt Cravets, Zhaoqing Ding, Thao Duong-Verlé, David Mattola, Robert F. Roscigno, Ravikumar Sitapara, Lawrence S. Zisman, Jean-Marie Bruey, Hossein-Ardeschir Ghofrani

Department of Medicine Faculty Publications

[Introduction] To the Editor: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by obstructive pulmonary arterial remodeling (1). Seralutinib, an investigational inhaled tyrosine kinase inhibitor, potently and selectively targets kinases relevant to PAH pathobiology including platelet-derived growth factor receptors (PDGFR) α and β, colony stimulating factor 1 receptor (CSF1R), and mast/stem cell growth factor receptor kit (c-KIT) (2). In preclinical models, seralutinib improved cardiopulmonary hemodynamics, reversed pulmonary vascular pathology and decreased right ventricular hypertrophy (3). In TORREY, a phase 2, multicenter, double-blind, randomized, placebo-controlled trial in PAH, seralutinib significantly reduced pulmonary vascular resistance (PVR) after 24 weeks with good …

Curing Duration Optimization To Reduce Shrinkage Cracking In One-Part Alkali-Activated Slag Concrete, A. Sadrmomtazi, H. Zanganeh

Journal of Sustainable Construction Materials and Technologies

The consequences of inadequate curing on one-part alkali-activated slag concrete (O-AAS) performance relative to ordinary Portland cement concrete (OPCC) have been investigated in this research. Prior to exposure to unsaturated conditions, samples underwent initial moist curing for durations ranging from 24 hours to one year. The testing program included compressive strength evaluation, chloride ion transport analysis, and measurement of free and restrained shrinkage. In addition, cylindrical cores were extracted from concrete columns to assess internal strength and chloride penetration resistance. Under unsaturated exposure, O-AAS exhibited a strength-aging phenomenon, with up to a 37% decrease in compressive strength over 360 days, …

Laboratory Investigation And Numerical Modelling Effect Of Carbon Nanotubes On Hot Mix Asphalt Permanent Displacement, Sepehr Saedi, Auwal Usman Nadada

Journal of Sustainable Construction Materials and Technologies

One of the primary causes of asphalt pavement deterioration is rutting; in contrast, one of the most effective methods to address this type of damage is the use of additives and quality evaluation during the design stages. In this research, laboratory testing and modeling using Abaqus software were employed to validate the laboratory results and predict and assess the potential for rutting. Carbon nanotubes (CNTs) were selected as an additive due to their exceptional mechanical properties and molecular interactions with bitumen. These nanotubes were used to modify the bitumen for the preparation of laboratory samples. The laboratory results from the …

Influence Of Early Microwave Curing On Performance Of Slag-Based Geopolymer Mortars, Ahmet Taşdemı̇R, Abdulkadir Çevı̇K

Journal of Sustainable Construction Materials and Technologies

In this article, an experimental study was conducted to examine the effect of curing time and microwave power on the compressive strength of early microwave-cured slag based geopolymers. Geopolymers have the potential to serve as an environmentally friendly substitute for cement-based building materials, and the use of microwave curing to geopolymers holds the promise of substantial strength improvement. Different microwave curing energies (300 - 800 Watts) were utilized at varying durations (10 - 60 minutes) on demoulded mortar specimens after one day. After that, compressive strength tests were conducted on both the cured and uncured specimens at three different ages: …

Use Of Alaçatı Stone Aggregate In Conventional And Self-Consolidating Concretes, Tahir Kemal Erdem

Journal of Sustainable Construction Materials and Technologies

Alaçatı stone or Alapietra stone is widely used mostly for building cladding. However, its production and use in the construction sites generate high amounts of waste (debris), causing environmental pollution in Çeşme which is a touristic district. This study investigated the reuse of Alaçatı stone as lightweight aggregate (LWA) in both conventional and self-consolidating concrete (SCC) mixtures. The concretes were prepared to have three different water-to-cement ratios (w/c), which were 0.38, 0.42 and 0.48. For each w/c, a conventional concrete mixture and two SCC mixtures with 60 or 70 cm slump flow were produced by varying the superplasticizer SP content. …

A Decision Support Model For Building Material And Component Reuse In The Context Of Circular Buildings, Havva Aksel

Journal of Sustainable Construction Materials and Technologies

Construction activities cause significant environmental impacts such as waste generation, pollution, resource consumption, and land use, which are expected to increase with global construction demands. To mitigate these environmental problems, the circular building occurs as an emerging concept depending on in the circular economy, which aims to minimize waste and redefine the “end-of-life” concept by reducing, reusing, recycling, and recovering materials. The reuse of building materials and components (BMCs) from existing structures represents a crucial strategy for achieving circularity in the built environment. Within this framework, design plays a key role. However, designing with reclaimed BMCs remains complex due to …

Optimization Of Research Pipeline To Characterize The Effects Of Atp-Sensitive Potassium Channels Mutations On Native Skeletal Muscle Fibers And Evaluate Potential Drug Therapy, Yuezhou Chen

McKelvey School of Engineering Graduate Student Theses & Dissertations

The ATP-sensitive potassium (KATP) channel is a critical metabolic sensor in skeletal muscle, yet its definitive molecular composition and functional roles remain contested. In this study, I conclusively demonstrate that the Kir6.2/SUR2 complex forms sarcolemmal KATP channel in mouse fast-twitch muscle. Genetic knock-out (KO) of Kir6.2 (Kcnj11−/−) or SUR2 (Abcc9−/−) resulted in a similar phenotype with increased fatigue resistance and a pathological rise in unstimulated resting tension at high-frequency stimulation. In contrast, SUR1 (Abcc8−/−) KO was ineffective. Furthermore, a CRISPR/Cas9 knock-in mouse model of a human SUR2A truncation variant (KCGV/KCGV) recapitulated the abnormal force accumulation, demonstrating that even loss-of-function of …

Functional Characterization Of Abcc8 Mutations Potentially Linked To The Transition From Hyperinsulinemic Hypoglycemia To Diabetes, Hao Zhang

McKelvey School of Engineering Graduate Student Theses & Dissertations

ATP-sensitive potassium (KATP) channels, composed of the SUR1 and Kir6.2 subunits encoded by the ABCC8 and KCNJ11 genes, are critical regulators of membrane excitability and insulin secretion in pancreatic β-cells. Gain-of-function (GOF) mutations in these genes cause neonatal diabetes mellitus through impaired insulin secretion and persistent hyperglycemia, whereas loss-of-function (LOF) mutations lead to congenital hyperinsulinism (CHI) with hypoglycemia due to β-cell hyperexcitability. I have addressed a paradoxical form of maturity-onset diabetes of the young (MODY) arising from KATP mutations, in which patients transition from CHI to glucose intolerance later in life. My experiments indicate that many KATP mutations associated with …

2d-Nanosilicate Carriers For Sustained Delivery Of Vaccine Components, Chih Yun Liu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Laponite® 2D Nanosilicates (NS) are disc-shaped platelets (~30 nm diameter, ~1 nm thick) with positively charged edges and negatively charged faces, capable of loading proteins, drugs, and nucleic acids via electrostatic interactions to form a house-of-cards gel that sequesters cargo. Here, we evaluated NS for sustained delivery of antigens and Toll-like receptor (TLR) agonists to extend germinal center duration and enhance antibody quality. The model antigen ovalbumin (OVA) was adsorbed onto NS at acidic pH in a ~1:1 ratio, with partial unfolding that remained stable at physiological pH. NS-OVA complexes were efficiently internalized by dendritic cells, with uptake driven primarily …

Durability Of Alkali-Activated Concretes Under 5% Sulfuric Acid Environment, Celal Karabaş, Anıl Niş

Journal of Sustainable Construction Materials and Technologies

The investigation focused on the resistance to 5% sulfuric acid degradation of the alkali-activated concretes (AAC). The AAC was manufactured using a blended binder of 50% slag and 50% F-type fly ash. The AAC was activated using a blend of 14 M sodium hydroxide and sodium silicate, with a hydroxide-to-silicate ratio of 1/2,5. Six AAC were produced against a 5% sulfuric acid environment, varying the binder amounts (400–500–600 kg/m3) and activator-binder (A/B) ratios (0,45–0,55). The chemical resistance of AAC was evaluated by visual appearance, variation in weight and compressive strengths. The findings pointed out that more gypsum and higher weight …

Comprehensive Risk Assessment For Construction Site Managers In Kosovo: A Mixed-Method Approach, Muhamet Ahmeti, Besian Sinani

Journal of Sustainable Construction Materials and Technologies

This study developed and validated a hybrid ISO 31000:2018 Kosovo-compliant risk assessment framework tailored for construction site managers operating within transitional economies. The research employed audits of 20 ISO-certified contractors in Pristina, Kosovo, along with field observations, interviews, and quantitative risk matrices. The findings indicate a critical concentration of risk, with 70% of firms classified as "High" or “Very High” risk. The most prevalent hazards identified were working at height without collective protection, unprotected electrical systems, and manual handling of heavy materials. Regression analysis revealed that firms with a designated safety champion achieved significantly lower risk scores, whereas those with …