Molecular, Cellular, and Tissue Engineering Commons^™

Fabrication And Evaluation Of Poly(Lactic Acid), Chitosan, And Tricalcium Phosphate Biocomposites For Guided Bone Regeneration, Srikanthan Ramesh, Lisa Lungaro, Dimitrios Tsikritsis, Eric Weflen, Iris V. Rivero

Industrial and Manufacturing Systems Engineering Publications

This study presents and evaluates an approach for fabricating poly(lactic acid) (PLA)/chitosan (CS)/tricalcium phosphate (TCP) electrospun scaffolds for guided bone regeneration, a dental procedure that uses membranes to direct and delineate regions of osteogenesis. Biomaterials were pre‐processed using cryomilling, a solid‐state grinding technique that facilitates the generation of powdered biocomposites conducive to electrospinning. X‐ray diffraction (XRD) confirmed the generation of cryomilled blends consisting of PLA, CS, and TCP. Results from the differential scanning calorimetry showed an upward shift in glass transition temperature and an increase in crystallinity with the inclusion of TCP reinforcing the ...

Modulating Viscoelasticity, Stiffness, And Degradation Of Synthetic Cellular Niches Via Stoichiometric Tuning Of Covalent Versus Dynamic Noncovalent Cross-Linking, Yu Tan, Henry Huang, David C. Ayers, Jie Song

Open Access Articles

Viscoelasticity, stiffness, and degradation of tissue matrices regulate cell behavior, yet predictive synergistic tuning of these properties in synthetic cellular niches remains elusive. We hypothesize that reversible physical cross-linking can be quantitatively introduced to synthetic hydrogels to accelerate stress relaxation and enhance network stiffness, while strategic placement of isolated labile linkages near cross-linking sites can predict hydrogel degradation, both of which are essential for creating adaptive cellular niches. To test these hypotheses, chondrocytes were encapsulated in hydrogels formed by biorthogonal covalent and noncovalent physical cross-linking of a pair of hydrophilic building blocks. The stiffer and more viscoelastic hydrogels with DBCO-DBCO ...

Tissue Clearing As A Mechanism To Identify Changes In Fibronectin Structure During Breast Cancer Metastasis, Maryam Nuru, Kelsey Hopkins, Luis Solorio

The Summer Undergraduate Research Fellowship (SURF) Symposium

With metastasis accounting for approximately 90% of breast cancer deaths and an alarming number of over 300,000 new breast cancer cases to be diagnosed by the end of 2018, there is growing need to understand the process of breast cancer. Changes in the extracellular matrix (ECM) of the tumor microenvironment play an essential role in this deadly tumor progression. Specifically, the glycoprotein fibronectin (FN), has been identified to be up-regulated in patients with worse clinical outcomes. During tumor progression fibronectin undergoes conformational changes that aid in metastatic dissemination. In order to analyze the dynamic changes in FN expression and ...

Characterization And Quantification Of Fibrin Gel Mechanics With Fibroblast Invasion, Nicklaus Iavagnilio, Sarah Calve, Adrian Buganza-Tepole

The Summer Undergraduate Research Fellowship (SURF) Symposium

Cutaneous wounds undergo an intricate healing process stimulated by a variety of local mechanical and biological stimuli that lead to patterns of growth and remodeling. Despite significant research in dermal wound healing, pathological scarring is still common particularly in wounds closed under mechanical stress, or large wounds left to heal by secondary intention. The purpose of this study is to utilize previously established wound healing models using fibrin gels and fibroblasts to better understand the functional relationships of the biological processes of normal compared to abnormal wound healing. Increases in uni-axial strain and transforming growth factor beta-1 concentration have been ...

Developing Droplet Based 3d Cell Culture Methods To Enable Investigations Of The Chemical Tumor Microenvironment, Jacqueline A. De Lora

Biomedical Sciences ETDs

Adaptation of cancer cells to changes in the biochemical microenvironment in an expanding tumor mass is a crucial aspect of malignant progression, tumor metabolism, and drug efficacy. In vitro, it is challenging to mimic the evolution of biochemical gradients and the cellular heterogeneity that characterizes cancer tissues found in vivo. It is well accepted that more realistic and controllable in vitro 3D model systems are required to improve the overall cancer research paradigm and thus improve on the translation of results, but multidisciplinary approaches are needed for these advances. This work develops such approaches and demonstrates that new droplet-based cell-encapsulation ...

Preparation And Characterization Of Functionalized Heparin-Loaded Poly-Ɛ-Caprolactone Fibrous Mats To Prevent Infection With Human Papillomaviruses, Daniela Gonzalez, Jorge Ragusa, Peter C. Angeletti, Gustavo F. Larsen

Chemical and Biomolecular Engineering -- All Faculty Papers

In this study, heparin-loaded poly-ε-caprolactone (PCL) fibrous mats were prepared and characterized based on their physical, cytotoxic, thermal, and biological properties. The main objective of the work described here was to test the hypothesis that incorporation of heparin into a PCL carrier could serve as bio-compatible material capable of inhibiting Human Papillomavirus (HPV) infection. The idea of firmly anchoring heparin to capture soluble virus, vs. a slow heparin release to inhibit a virus in solution was tested. Thus, one material was produced via conventional heparin matrix encapsulation and electrohydrodynamic fiber processing in one step. A second type of material was ...

Developmental Steps For A Functional Three-Dimensional Cell Culture System For The Study Of Asymmetrical Division Of Neural Stem Cells, Martina Zamponi

Biomedical Engineering Theses & Dissertations

Stem cells are a cell type present during and following development, which possess self- renewal properties, as well as the ability to differentiate into specific cells. Asymmetrical division is the cellular process that allows stem cells to produce one differentiated and one un-differentiated daughter cell during the same mitotic event. Insights in the molecular mechanisms of such process are minimal, due to the absence of effective methods for its targeted study. Currently, traditional methods of investigation include monolayer cell culture and animal models. The first poses structural limitations to the accurate representation of human tissue and cell structures, while animal ...

Chemically Modified Gellan Gum Hydrogels With Tunable Properties For Use As Tissue Engineering Scaffolds, Zihao Xu, Zhuqing Li, Shan Jiang, Kaitlin M. Bratlie

Chemical and Biological Engineering Publications

Gellan gum is a naturally occurring polymer that can cross-link in the presence of divalent cations to form biocompatible hydrogels. However, physically cross-linked gellan gum hydrogels lose their stability under physiological conditions, thus restricting the applications of these hydrogels in vivo. To improve the mechanical strength of the gels, we incorporated methacrylate into the gellan gum and chemically cross-linked the hydrogel through three polymerization methods: step growth through thiol–ene photoclick chemistry, chain-growth via photopolymerization, and mixed model in which both mechanisms were employed. Methacrylation was confirmed and quantified by proton nuclear magnetic resonance (1H NMR) and Fourier transform infrared ...

Modeling Pharmaceutical Inhibition Of Glucose-Stimulated Renin-Angiotensin System In Kidneys, Ashlee N. Ford Versypt, Minu R. Pilvankar, Hui Ling Yong

Biology and Medicine Through Mathematics Conference

No abstract provided.

Soft-Microrobotics: The Manipulation Of Alginate Artificial Cells, Samuel Sheckman

Mechanical Engineering Research Theses and Dissertations

In this work, the approach to the manipulation of alginate artificial cell soft-microrobots, both individually and in swarms is shown. Fabrication of these artificial cells were completed through centrifugation, producing large volumes of artificial cells, encapsulated with superparamagnetic iron oxide nanoparticles; these artificial cells can be then externally stimulated by an applied magnetic field. The construction of a Permeant Magnet Stage (PMS) was produced to manipulate the artificial cells individually and in swarms. The stage functionalizes the permanent magnet in the 2D xy-plane. Once the PMS was completed, Parallel self-assembly (Object Particle Computation) using swarms of artificial cells in complex ...

Designing Synthetic Environments To Control Valvular Interstital Cells In Vitro, Kent E. Coombs

Biomedical Sciences ETDs

Aortic valve disease (AVD) is a large contributor to health costs in the United States affecting 2.8% of the population greater than 75 years old. With a growing elderly population due to medical advances, AVD will continue to rise in prevalence over time. Current treatments for AVD are insufficient due to a lack of preventative therapies and the bioprosthetic valves used for surgical replacement have major limitations. Tissue engineered heart valves (TEHVs) present an ideal solution to current AVD needs because of their biocompatibility, capability to integrate with the host’s tissue, and ability to utilize the natural repair ...

Mitochondrial Mrna Translation Is Required For Maintenance Of Oxidative Capacity, David Lee

Theses and Dissertations

Oxidative metabolism is required to produce adequate energy to sustain human life. A primary example of deteriorating oxidative capacity is seen in the cardiac musculature during chronic heart failure. This suggests that by improving oxidative potential, chronic heart disease could be mitigated and one approach to accomplish this may be through targeting the mt-mRNA translation system. Purpose: This investigation’s purpose was to characterize disruptions in mt-mRNA translation machinery in multiple forms of cardiomyopathy and to determine if mitochondrial mRNA translation initiation factor (mtIF2) is necessary to maintain oxidative capacity in cardiomyocytes. Methods Using a combination of animal and cell ...

Novel Methodology For Emboli Analog Production And In-Vitro Simulation Of Acute Ischemic Stroke, Anne Preut

Theses and Dissertations

Stroke is the leading cause of disability and a primary cause of mortality, resulting in an estimated $33 billion dollars spent on healthcare, rehabilitation and lost productivity in the United States each year. The most prevalent cause of stroke incidents are acute ischemic events, manifested as blood clots in the vasculature supplying the brain. Current gold standard treatments have improved since 2006 with the introduction of mechanical stent retrievers; however, several issues with the current treatments to acute ischemic stroke remain. Thrombolysis of the clot with a tissue plasminogen activator may lead to weakening the vessel wall and consequently, hemorrhaging ...

Structure And Property Of Polymers And Biopolymers From Molecular Dynamic Simulations, Xiaoquan Sun

Theses and Dissertations

Natural and synthetic polymers and biopolymers have been studied for a variety of applications in food emulsion, biopharmaceutical purification, tissue engineering, and biosensor. The structure and property of polymers and biopolymers are critically important to determine their functions. Molecular dynamics (MD) simulations have a unique advantage to explore the structure and property of polymers and biopolymers from the molecular level. In the dissertation, MD simulations were conducted to study the mechanisms of various biological and chemical processes controlled by polymers and biopolymers based on real-world experimental results.

Seven heptapeptides have been screened from a peptide library in our earlier study ...

Plga-Modified Nanoparticles For The Treatment Of Hypo-Vascularized Hpv-Related Cervical Cancers., Lee B. Sims

Electronic Theses and Dissertations

A major challenge associated with delivery of active agents in the female reproductive tract (FRT) is the ability of agents to efficiently diffuse through the cervicovaginal mucosa (CVM) and reach the underlying sub-epithelial immune cell layer and vasculature. A variety of drug delivery vehicles have been employed to improve the delivery of agents across the CVM and offer the capability to increase the longevity and retention of active agents to treat infections of the female reproductive tract. Nanoparticles (NPs) have been shown to improve retention, diffusion, and cell-specific targeting via specific surface modifications, relative to other delivery platforms. In particular ...

Investigation Of Cardiovascular Tissue Following 56fe-Radiation And Potential Countermeasure Effectiveness., Alexandra R Decarlo

Electronic Theses and Dissertations

Exposure to ionizing radiation is an important medical concern because it can lead to health problems including cancer and cardiovascular issues. In space, astronauts are exposed to ionizing radiation that is not experienced by those who remain on Earth. This radiation can cause health problems such as cardiovascular disease. One way this can happen is through the creation of reactive oxygen species, which can activate TGF-β1, contributing to fibrosis or other cardiovascular problems. Antioxidants can be a potential pharmacological mitigator of these excess reactive oxygen species because of their ability to neutralize reactive oxygen species. One such antioxidant with potential ...

Armms As A Versatile Platform For Intracellular Delivery Of Macromolecules, Qiyu Wang, Jiujiu Yu, Tatenda Kadungure, Joseph Beyene, Hong Zhang, Quan Lu

Pediatric Publications and Presentations

Majority of disease-modifying therapeutic targets are restricted to the intracellular space and are therefore not druggable using existing biologic modalities. The ability to efficiently deliver macromolecules inside target cells or tissues would greatly expand the current landscape of therapeutic targets for future generations of biologic drugs, but remains challenging. Here we report the use of extracellular vesicles, known as arrestin domain containing protein 1 [ARRDC1]-mediated microvesicles (ARMMs), for packaging and intracellular delivery of a myriad of macromolecules, including the tumor suppressor p53 protein, RNAs, and the genome-editing CRISPR-Cas9/guide RNA complex. We demonstrate selective recruitment of these macromolecules into ...

A Synthetic, Three-Dimensional Bone Marrow Hydrogel, Lauren Jansen, Thomas Mccarthy, Michael J. Lee, Shelly Peyton

University of Massachusetts Medical School Faculty Publications

Three-dimensional (3D) synthetic hydrogels have recently emerged as desirable in vitro cell culture platforms capable of representing the extracellular geometry, elasticity, and water content of tissue in a tunable fashion. However, they are critically limited in their biological functionality. Hydrogels are typically decorated with a scant 1-3 peptide moieties to direct cell behavior, which vastly underrepresents the proteins found in the extracellular matrix (ECM) of real tissues. Further, peptides chosen are ubiquitous in ECM, and are not derived from specific proteins. We developed an approach to incorporate the protein complexity of specific tissues into the design of biomaterials, and created ...

Covalently Crosslinked Organic/Inorganic Hybrid Biomaterials For Bone Tissue Engineering Applications, Dibakar Mondal

Electronic Thesis and Dissertation Repository

Scaffolds are key components for bone tissue engineering and regeneration. They guide new bone formation by mimicking bone extracellular matrix for cell recruitment and proliferation. Ideally, scaffolds for bone tissue engineering need to be osteoconductive, osteoinductive, porous, degradable and mechanically competent. As a single material can not provide all these requirements, composites of several biomaterials are viable solutions to combine various properties. However, conventional composites fail to fulfil these requirements due to their distinct phases at the microscopic level. Organic/inorganic (O/I) class II hybrid biomaterials, where the organic and inorganic phases are chemically crosslinked on a molecular scale ...

Eigenstrain As A Mechanical Set-Point Of Cells, Shengmao Lin, Marsha C. Lampi, Cynthia A. Reinhart-King, Gary C.P. Tsui, Jian Wang, Carl A. Nelson, Linxia Gu

Mechanical & Materials Engineering Faculty Publications

Cell contraction regulates how cells sense their mechanical environment. We sought to identify the set-point of cell contraction, also referred to as tensional homeostasis. In this work, bovine aortic endothelial cells (BAECs), cultured on substrates with different stiffness, were characterized using traction force microscopy (TFM). Numerical models were developed to provide insights into the mechanics of cell–substrate interactions. Cell contraction was modeled as eigenstrain which could induce isometric cell contraction without external forces. The predicted traction stresses matched well with TFM measurements. Furthermore, our numerical model provided cell stress and displacement maps for inspecting the fundamental regulating mechanism of ...