Translational Medical Research Commons^™

Volumetric Wear Analysis Of Polyethylene Orthopedic Liners Using Point Clouds, Gabriel Landi

Dartmouth College Master’s Theses

In vivo wear of ultra-high molecular weight polyethylene (UHMWPE) orthopedic bearings represents a major problem in shoulder and knee arthroplasty, with significant amounts of devices failing due to the complication itself, and even more due to associated reasons for retrieval, including aseptic loosening. However, quantification of UHMWPE wear has largely been limited to linear and in vitro volumetric analyses, obscuring the understanding of the amount of clinically relevant material loss. This study proposes new methods to measure articular, rim, and backside surfaces of retrieved shoulder and knee UHMWPE liners, centered around the coordinate measuring machine (CMM)-based collection of high density …

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 …

A Chicken Model For Non-Invasive Diagnosis Of Infant Developmental Dysplasia Of The Hip (Ddh) Using Acoustic Transmission Measurements, Aliza Shah

Honors Undergraduate Theses

Developmental dysplasia of the hip (DDH) is a condition characterized by abnormal development and stability of the hip joint. In a healthy infant, the femoral head (ball) fits securely within the acetabulum (socket of the pelvis), allowing for proper joint function. In DDH, the relationship is disrupted, ranging from mild acetabular dysplasia to partial (subluxation) or complete dislocation of the femoral head. This condition represents a range of structural abnormalities that develop during early growth. The integrity of the hip joint is essential for physical mobility, and disruption of this structure can lead to significant functional impairment. DDH may result …

A Novel Scaffold-Based Model For Stage Ii Pressure Injury Simulation: Protocol Development And Future Directions In Tissue Engineering, Skyler B. Wrubleski

Undergraduate Research and Scholarship Symposium

This study developed a 3D tissue-engineered scaffold to mimic human sacral skin for modeling pressure injuries. The scaffold consisted of a composite hydrogel of sodium alginate, gelatin, and tannic acid, crosslinked with calcium chloride. Swelling tests showed moderate hydration capacity, while wound mimic formation using a custom 3D-printed apparatus produced consistent morphology and dimensions comparable to human dermal tissue. The scaffold maintained structural integrity under prolonged compressive forces, demonstrating viability for pressure injury studies. Future work will incorporate a bilayer model with keratinocytes and fibroblasts and introduce elastin to enhance elasticity and mechanical properties. This approach aims to improve in …

Advancing Novel Contrast Agents For Applications In Fluorescence-Guided Neurosurgery Using Fluorescence Cryotomography, Augustino Vittorio Scorzo

Dartmouth College Ph.D Dissertations

Fluorescence guided surgery (FGS) is an emerging surgical technique that aims to help surgeons identify tissue types to assist in surgical decision making - ideally providing “cut-by-color” guidance. A primary application for this approach is the identification of tumor tissue to achieve more accurate and complete tumor removal while simultaneously minimizing damage to surrounding normal tissue. The cornerstone of tumor visualization for FGS is the administration of fluorescent contrast agents, or in some cases metabolic precursors, designed to accumulate specifically in tumor tissue, and a wide range of agents that use different targeting mechanisms are currently under investigation. Although these …

Mechanistic Insights Into The Flash Effect: The Role Of Oxygen And Radiation Chemistry In Ultra-High Dose Rate Radiation Therapy, Jacob Pierce Sunnerberg

Dartmouth College Ph.D Dissertations

The development of new cancer therapies focuses on widening the therapeutic ratio between tumor control and normal tissue toxicity. Over the last decade, ultra-high dose rate (UHDR) radiation therapy, commonly known as FLASH radiotherapy (FLASH-RT), has shown promising potential to reduce normal tissue toxicity while maintaining tumor control. However, the underlying mechanisms of the FLASH effect remain poorly understood. This thesis explores the radiation-chemical basis of FLASH-RT, focusing on the role of oxygen and reactive oxygen species in modulating biological outcomes.

A comprehensive set of in vitro studies demonstrated that UHDR delivery significantly alters radiation chemistry compared to conventional dose …

Toward The Application Of Natural Language Processing In Electronic Health Record Analysis For Taxonomy Development, Latoya Mcdonald

All Dissertations

Electronic health records (EHRs) are pivotal resources for nurse practice because they increase the timeliness and reliability of patient information at the point of care and support access by multiple healthcare providers and the individual patients themselves. However, it is widely recognized that data extraction from EHRs is challenging due to the variability in the language used in clinical care notes and the lack of standardized terminology across healthcare systems. The broad objective of this dissertation is to develop taxonomy-based classification models for nursing care by applying feature engineering approaches to EHRs that include nursing care of ostomy patients following …

Novel Electrophysiological Biomarkers In Pediatric Drug Resistant Epilepsy And Genetic Epilepsy Syndromes, Sakar Rijal

Bioengineering Dissertations - Archive

Pediatric epilepsies, particularly those that are drug-resistant or genetically driven, represent some of the most complex neurological disorders encountered in childhood. Central to their pathophysiology is a disruption in the delicate balance between cortical excitation and inhibition (E/I), often resulting from impaired GABAergic interneuron function. This imbalance manifests as aberrant network dynamics and altered neural oscillations, giving rise to seizures and long-term cognitive impairments. In this thesis, we developed a translational framework to identify electrophysiological biomarkers that (i) assess cortical E/I imbalance and (ii) map epileptogenic zones, with the aim of enhancing diagnosis, guiding surgical planning, and informing therapeutic monitoring …

Fabricating Silver-Ceria Polymer Nanocomposite Scaffolds For Biomedical Therapeutic Applications, Shreya S. Pawar

Honors Undergraduate Theses

Improper healing of bone fractures and limited regeneration of bone following bone tumor resection remain a prevalent complication worldwide. Long-term effects of this include joint instability, limited movement, and arthritis. Bone infections (osteomyelitis), reactive oxygen species (ROS) generation via excessive inflammation, and underlying conditions such as osteoporosis can contribute to suboptimal bone tissue regeneration. ROS accumulation stimulates osteoblast apoptosis, while promoting osteoclast differentiation. These processes inhibit mineralization and osteogenesis. Conventional therapeutics involve the utilization of drugs and bone grafts. However, these approaches pose limitations and can result in subsequent complications. Microbial infections, ROS accumulation, and excessive inflammations are factors that …

No Difference In Pullout Strength Between A Bio-Inductive Implant And A Semitendinosus Tendon Graft In A Biomechanical Study Of Medial Patellofemoral Ligament Repair Augmentation, Austin Wetzler, Sean Mcmillan, Erik Brewer, Aakash Patel, Samuel Handy, Merrick Wetzler

Rowan-Virtua School of Translational Biomedical Engineering & Sciences Departmental Research

Purpose: To compare the pullout strength of a bio-inductive implant (BI) used to augment a medial patellofemoral ligament (MPFL) repair with the pullout strength of semitendinosus graft in a biomechanical cadaveric model. Methods: Six matched pairs of cadavers (12 knees) were used in the biomechanical testing comparing semitendinosus tendon (Semi-T) versus a BI. The Semi-T was harvested from 1 of the matched pairs. A standard double-bundle technique using 2 sockets in the upper two-thirds of the patella 15 mm apart was performed. After docking of the graft into the patella, the patella was dissected free of soft tissues and potted …

Novel Engineering Approaches For Orthopedic Injury Treatment And Infection Diagnosis, Cynthia Co

Bioengineering Dissertations - Archive

Bioengineering has made significant contributions to the treatment of orthopedic injury through interdisciplinary approaches. Central to these advancements are many orthopedic implants, including anchors and joint replacements, which have been designed to restore mobility. Despite their functional efficacy, these products have limited lifespan and are associated with many complications, such as implant-associated infection. The success of implant design and function, both in the short and long term, is paramount for enhancing patient outcomes and overall well-being. Therefore, my thesis work is dedicated to addressing these critical challenges, aiming to maximize their treatment effect while minimizing the implant-associated complications.

Long-term patient …

Evaluation Of Silk Fibroin And Hylauronic Acid As Otic Drug Delivery System Additives; Investigation Of Silk Fibroins Responses To Enviromental Stimulii, Kolton Charles Sandau

Graduate Student Theses, Dissertations, & Professional Papers

The Serban lab has previously developed and reported on a single application drug delivery system for the treatment of otitis externa. Otitis externa also known as outer ear infections is a very common ailment that impacts large portions of both human and domestic animal populations. Typical treatment for otitis externa typically requires an extended dosing regimen over several days that is inconvenient and can lead to poor clinical outcomes due to poor patient compliance. Our delivery system employs a thixotropic gel to deliver a steady dose of medication over the duration of the infection.

Here we evaluated the reproducibility and …

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

Prevention And Reversal Of Elastin-Associated And Phosphate-Dependent Arterial Calcification Using Targeted Nanotherapeutics In Pre-Clinical Models, Fatema Tuj Zohora

All Dissertations

Vascular calcification can be life-threatening, involving calcium phosphate crystal deposits in the blood vessels. The calcification in the intimal layer of the arterial wall is usually associated with atherosclerotic plaque build-up that, in the advanced stage, harbors ‘dispersed’ and ‘spotty’ deposits of calcium phosphate crystals in the necrotic core of the plaque. In contrast, medial arterial calcification (MAC) can form independently of atherosclerosis and appears as ‘Railroad-like’ calcific deposits along degraded elastin lamellae in the medial layer of arteries. The mechanisms of such elastin-associated medial arterial calcification and potential therapies are the key concerns of this dissertation. MAC is common …

Noninvasively Monitoring Of Cerebral Blood Flow In Piglet Models Of Graded Hemorrhage And Hypoxic Ischemic Brain Injury Using Diffuse Correlation Spectroscopy And Near-Infrared Spectroscopy, Randolph Sinahon, Danielle Shoshany, Shadi Malaeb, Mert Deniz Polat, Meltem Izzetoglu, Kurtulus Izzetoglu

St. Chris Research Day

No abstract provided.

Regenerative Medicine For Tendon/Ligament Injuries: De Novo Equine Tendon/Ligament Neotissue Generation And Application, Takashi Taguchi

LSU Doctoral Dissertations

Tendon and ligament injuries are debilitating conditions across species. Poor regenerative capacities of these tissues limit restoration of original functions. The first study evaluated the effect of cellular administration on tendon/ligament injuries in horses using meta-analysis. The cellular administration was effective in restoring ultrasonographic echogenicity and increasing vascularity during early phase of healing. Additionally, it improved microstructural organization of healed tissue in terms of cellularity and fiber alignment. However, the study did not support its use for increasing rate of return to performance, expression/deposition of tendon-specific genes/proteins, or mechanical properties.

The findings led to the second study that engineered implantable …

Sodium Hyaluronate Based Drug Delivery To The Outer And Inner Ear, Emma Barrett-Catton

Graduate Student Theses, Dissertations, & Professional Papers

We have developed two projects using sodium hyaluronate (HA)-based systems for drug delivery to the ear. First, we investigated an HA-based hydrogel for use as a single use antibiotic treatment for otitis externa. Otitis externa, also known as outer ear infection, is a frequent affliction in both humans and animals. The most prevalent treatment for otitis externa is ear drops, but it is difficult to adhere properly to this treatment, causing poor patient compliance and the potential for complications. As a result, we have developed an HA-based hydrogel for use as a single application treatment for otitis externa to increase …

Use Of Bioheat Modeling To Characterize And Optimize Implantable Medical Devices And Neuromodulation Technologies, Adantchede Louis Zannou

Dissertations and Theses

Medical device development includes prototyping, benchtop characterization, preclinical studies, and clinical trials. Understanding the limitations and potential adverse effects of medical devices prior to their administration in humans is a crucial first step. Optimizing medical devices is essential to employing technology and improving patients care. Computational modeling is widely adopted as a powerful tool to predict stimulation/recording parameter optimization, rapid electrode/device prototyping, investigating novel mechanism of action, and testing working principles of any medical devices. Many implantable neuromodulation technologies including Spinal Cord Stimulation (SCS), which provide substantial therapeutic benefit for patient population with lower back pain, produces heat via the …

Leveraging Cell-Substrate Adhesion And Cell Migratory Properties In Skeletal Muscle Constructs And Cancer Metastasis Assays, Lauren E. Mehanna

Theses and Dissertations--Chemical and Materials Engineering

Volumetric muscle loss (VML) remains one of the few skeletal muscle injuries without a reliable and repeatable treatment. In large volume muscle injuries, muscle fibers as well as the surrounding connective tissue are damaged, preventing therapeutic muscle stem cells, called myogenic progenitor cells (MPCs), from reaching the injury site and initiating repair. There is a clinical need to rapidly fabricate in vitro muscle tissue constructs that mimic the native tissue organization, with aligned myotubes, for insertion and integration at the patient’s injury site. In this dissertation, we utilize the MPC’s natural propensity to close gaps across an injury site to …

The Role Of Generative Adversarial Networks In Bioimage Analysis And Computational Diagnostics., Ahmed Naglah

Electronic Theses and Dissertations

Computational technologies can contribute to the modeling and simulation of the biological environments and activities towards achieving better interpretations, analysis, and understanding. With the emergence of digital pathology, we can observe an increasing demand for more innovative, effective, and efficient computational models. Under the umbrella of artificial intelligence, deep learning mimics the brain’s way in learn complex relationships through data and experiences. In the field of bioimage analysis, models usually comprise discriminative approaches such as classification and segmentation tasks. In this thesis, we study how we can use generative AI models to improve bioimage analysis tasks using Generative Adversarial Networks …

Role Of Deep Learning Techniques In Non-Invasive Diagnosis Of Human Diseases., Hisham Abouelseoud Elsayem Abdeltawab

Electronic Theses and Dissertations

Machine learning, a sub-discipline in the domain of artificial intelligence, concentrates on algorithms able to learn and/or adapt their structure (e.g., parameters) based on a set of observed data. The adaptation is performed by optimizing over a cost function. Machine learning obtained a great attention in the biomedical community because it offers a promise for improving sensitivity and/or specificity of detection and diagnosis of diseases. It also can increase objectivity of the decision making, decrease the time and effort on health care professionals during the process of disease detection and diagnosis. The potential impact of machine learning is greater than …

Development Of A Decellularized Hydrogel Composite And Its Application In A Novel Model Of Disc-Associated Low Back Pain In Female Sprague Dawley Rats, David Lillyman

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Chronic low back pain is a global socioeconomic crisis compounded by an absence of reliable, curative treatments. The predominant pathology associated with chronic low back pain is degeneration of intervertebral discs in the lumbar spine. During degeneration, nerves can sprout into the intervertebral disc tissue and be chronically subjected to inflammatory and mechanical stimuli, resulting in pain. Pain arising from the intervertebral disc, or disc-associated pain, is a complex, multi-faceted disorder which necessitates valid animal models to screen therapeutics and study pathomechanisms of pain.

While many research teams have created animal models of disc degeneration, the translation of these platforms …

Development And Application Of 3d Kinematic Methodologies For Biomechanical Modelling In Adaptive Sports And Rehabilitation, Anne Marie Severyn

All Dissertations

Biomechanical analysis is widely used to assess human movement sciences, specifically using three-dimensional motion capture modelling. There are unprecedented opportunities to increase quantitative knowledge of rehabilitation and recreation for disadvantaged population groups. Specifically, 3D models and movement profiles for human gait analysis were generated with emphasis on post-stroke patients, with direct model translation to analyze equivalent measurements while horseback riding in use of the alternative form of rehabilitation, equine assisted activities and therapies (EAAT) or hippotherapy (HPOT). Significant improvements in gait symmetry and velocity were found within an inpatient rehabilitation setting for patients following a stroke, and the developed movement …

Optimizing Biomedical Discoveries As An Engine Of Culture Change In An Academic Medical Center, Anne K. Dechant, Stephen Fening, Michael Haag, William Harte, Mark R. Chance

Faculty Scholarship

Academic discovery in biomedicine is a growing enterprise with tens of billions of dollars in research funding available to universities and hospitals. Protecting and optimizing the resultant intellectual property is required in order for the discoveries to have an impact on society. To achieve that, institutions must create a multidisciplinary, collaborative system of review and support, and utilize connections to industry partners. In this study, we outline the efforts of Case Western Reserve University, coordinated through its Clinical and Translational Science Collaborative (CTSC), to promote entrepreneurial culture, and achieve goals of product development and startup formation for biomedical and population …

Exosome- And Microrna-Based Therapeutic Approach For Tendinopathy, Angela Wang Ilaltdinov

Dissertations and Theses

Tendinopathy, characterized by degeneration and chronic inflammation, is a significant clinical burden. Current treatments focus on symptom management but do not sufficiently address its underlying pathology; however, stem cell-based approaches aimed at repairing diseased tissues may overcome this limitation. Therapeutic effects of stem cells may be due in part to paracrine actions, including some mediated by exosomes – extracellular vesicles secreted by cells that play a role in cell communication. MicroRNA (miRNA), small non-coding RNA carried by exosomes, are likely responsible for many exosome effects. Exosomes and miRNA therapies show promise in treating diseases such as cancer and arthritis, but …

A Fully-Automated, Deep Learning-Based Framework For Ct-Based Localization, Segmentation, Verification And Planning Of Metastatic Vertebrae, Tucker Netherton, Tucker James Netherton

Dissertations and Theses (Open Access)

Palliative radiotherapy is an effective treatment for the palliation of symptoms caused by vertebral metastases. Visible evidence of disease is localized on medical images as part of the treatment planning process. However, complicating factors such as time pressures, anatomic variants in the spine, and similarities in adjacent vertebrae are associated with wrong level treatments of the spine. In addition, erroneous manual contouring of anatomic structures is a major failure mode in radiotherapy treatment planning.

The purpose of this study is to mitigate the challenges associated with treatment planning of the spine by automating the treatment planning process for three-dimensional conformal …

Intermittent Theta Burst Stimulation: Application To Spinal Cord Injury Rehabilitation And Computational Modeling, Neil Mittal

Theses and Dissertations

Loss of motor function from spinal cord injuries (SCI) results in loss of independence. Rehabilitation efforts are targeted to enhance the ability to perform activities of daily living (ADLs), but outcomes from physical therapy alone are often insufficient. Neuromodulation techniques that induce neuroplasticity may push the limits on recovery. Neuromodulation by intermittent theta burst transcranial magnetic stimulation (iTBS) induces neuroplasticity by increasing corticomotor excitability, though this has most frequently been studied with motor targets and on individuals not in need of rehabilitation. Increased corticomotor excitability is associated with motor learning. The response to iTBS, however, is highly variable and unpredictable, …

Development Of A Pediatric Cardiac Assist Maglev Pump For Use With A Universal Driver System., Landon Heath Tompkins

Electronic Theses and Dissertations

Heart failure (HF) remains the leading cause of death, affecting 26 million adults worldwide and 6.5 million adults in the United States. Pediatric HF patients have been a historically underserved population with few options for mechanical circulatory support (MCS) therapy, a leading treatment as an alternative to heart transplantation. To address this clinical need, the Inspired Universal MagLev System is being developed; a low cost, universal magnetically levitated extracorporeal MCS system with interchangeable single-use pumps that will ultimately provide adult and pediatric patients ventricular and respiratory assist therapies. The Inspired Pediatric VAD is the first single-use pump application for this …

Modeling, Fabrication And Characterization Of Coated Calcium Phosphate Scaffolds Produced By 3d-Printing For Tissue Engineering Application, Touri Maria

Student Works (2020-2029)

A fully interconnected 3-dimensional scaffold with pre-determined dimensions and porosity can be attained by design-dependent rapid prototyping techniques which possess precise control over the internal and external architecture of the scaffolds thus they can overcome the problems associated with the process-dependent classical approaches. Interruption of vascular flow with fracture or surgical osteotomy results in a transient hypoxic gradient within the wound and subsequent tissue necrosis. Tissue engineering scaffolds with oxygen generating elements have shown to be able to increase the level of oxygen and cell survivability. In this study, biphasic calcium phosphate (BCP) scaffolds with the composition of 60% hydroxyapatite …

Development Of Fully Balanced Ssfp And Computer Vision Applications For Mri-Assisted Radiosurgery (Mars), Jeremiah Sanders

Dissertations and Theses (Open Access)

Prostate cancer is the second most common cancer in men and the second-leading cause of cancer death in men. Brachytherapy is a highly effective treatment option for prostate cancer, and is the most cost-effective initial treatment among all other therapeutic options for low to intermediate risk patients of prostate cancer. In low-dose-rate (LDR) brachytherapy, verifying the location of the radioactive seeds within the prostate and in relation to critical normal structures after seed implantation is essential to ensuring positive treatment outcomes.

One current gap in knowledge is how to simultaneously image the prostate, surrounding anatomy, and radioactive seeds within the …