A5079299741- Cardiac Valve Diseases and Treatments
- Electrospun Nanofibers in Biomedical Applications
- Connective tissue disorders research
- Aortic Disease and Treatment Approaches
- 3D Printing in Biomedical Research
- Infective Endocarditis Diagnosis and Management
- Bone and Dental Protein Studies
- Tribology and Lubrication Engineering
- Cellular Mechanics and Interactions
- Ion Channels and Receptors
- Fuel Cells and Related Materials
- Meat and Animal Product Quality
- Postharvest Quality and Shelf Life Management
- Platelet Disorders and Treatments
- COVID-19 Clinical Research Studies
- Sex and Gender in Healthcare
- Aortic aneurysm repair treatments
- Hip disorders and treatments
- Hydrogels: synthesis, properties, applications
- Tissue Engineering and Regenerative Medicine
- Viral Infectious Diseases and Gene Expression in Insects
- Cardiovascular Function and Risk Factors
- SARS-CoV-2 and COVID-19 Research
- Streptococcal Infections and Treatments
- Cardiovascular Effects of Exercise
Wellborn Road Veterinary Medical Center
2022-2023
University of Colorado Boulder
2018-2022
Howard Hughes Medical Institute
2016
Background: Aortic valve stenosis is a sexually dimorphic disease, with women often presenting sustained fibrosis and men more extensive calcification. However, the intracellular molecular mechanisms that drive these clinically important sex differences remain underexplored. Methods: Hydrogel biomaterials were designed to recapitulate key aspects of tissue microenvironment serve as culture platform for sex-specific valvular interstitial cells (VICs; precursors profibrotic myofibroblasts)....
Objective: Resident valvular interstitial cells (VICs) activate to myofibroblasts during aortic valve stenosis progression, which further promotes fibrosis or even differentiate into osteoblast-like that can lead calcification of tissue. Inflammation is a hallmark stenosis, so we aimed determine proinflammatory cytokines secreted from M1 macrophages give rise transient VIC phenotype leads Approach and Results: We designed hydrogel biomaterials as extracellular matrix mimics enabling the...
Materials that are resistant to nonspecific protein adsorption critical in the biomedical community. Specifically, nonfouling implantable biomaterials necessary reduce undesirable, but natural foreign body response. The focus of this investigation is demonstrate polyampholyte hydrogels prepared with equimolar quantities positively charged [2-(acryloyloxy)ethyl] trimethylammonium chloride (TMA) and negatively 2-carboxyethyl acrylate (CAA) monomers a viable solution problem. TMA/CAA were their...
Abstract Aortic valve stenosis (AVS) is a progressive fibrotic disease that caused by thickening and stiffening of leaflets. At the cellular level, quiescent interstitial cells (qVICs) activate to myofibroblasts (aVICs) persist within tissue. Given persistence in AVS, epigenetic mechanisms have been implicated. Here, we studied changes occur VICs during myofibroblast activation using hydrogel matrix recapitulate different stiffnesses leaflet fibrosis. We first compared chromatin landscape...
In their native extracellular microenvironment, cells respond to a complex array of biochemical and mechanical cues that can vary in both time space. High-throughput methods allow characterization cell-laden matrices are valuable tools screen through many combinations variables, ultimately helping evolve test hypotheses related cell–ECM signaling. Here, we developed platform for high-throughput encapsulation peptide-functionalized poly(ethylene glycol) hydrogels. Hydrogels were synthesized...
Documented natural infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in exotic and companion animals following human exposures are uncommon. Those documented typically mild self-limiting, infected have only infrequently died or been euthanized. Through a coordinated One Health initiative, necropsies were conducted on 5 from different premises that exposed to humans laboratory-confirmed SARS-CoV-2 infection. The combination of epidemiologic evidence exposure...
Valvular interstitial cells (VICs) are responsible for the maintenance of extracellular matrix in heart valve leaflets and, response to injury, activate from a quiescent fibroblast wound healing myofibroblast phenotype. Under normal conditions, activation is transient, but chronic presence activated VICs can lead diseases, such as fibrotic aortic stenosis, which non-surgical treatments remain elusive. We monitored porcine VIC exogenously delivered growth factor 2 (FGF-2; 100 ng/ml),...
Pro-inflammatory cytokines play critical roles in regulating valvular interstitial cell (VIC) phenotypic changes that can cause heart valve fibrosis and calcification. Tumor necrosis factor alpha (TNF-α) is a cytokine known to influence VIC behavior has been reported at high levels calcified valves ex vivo. We sought understand the specific effects of TNF-α on phenotypes (eg, fibroblast, profibrotic activated myofibroblasts) its link with disorders. characterize human aortic tissue from...
Abstract The role viscoelasticity in fibrotic disease progression is an emerging area of interest. Here, a fast‐relaxing hydrogel system exploited to investigate potential crosstalk between calcium signaling and mechanotransduction. Poly(ethylene glycol) (PEG) hydrogels containing boronate triazole crosslinkers are synthesized, with varying ratios crosslinks systematically vary the extent stress relaxation. Valvular interstitial cells (VICs) encapsulated highest levels relaxation (90%)...
As aortic valve stenosis develops, tissue becomes stiffer. In response to this change in environmental mechanical stiffness, valvular interstitial cells (VICs) activate into myofibroblasts. We aimed investigate the role of mechanosensitive calcium channel Transient Receptor Potential Vanilloid type 4 (TRPV4) stiffness induced myofibroblast activation. verified TRPV4 functionality VICs using live imaging during application small molecule modulators activity. designed hydrogel biomaterials...
Patients with aortic valve stenosis (AVS) have sexually dimorphic phenotypes in their tissue, where male valvular tissue adopts a calcified phenotype and female becomes more fibrotic. The molecular mechanisms that regulate sex-specific calcification remain poorly understood. Here, we explored the role of osteopontin (OPN), pro-fibrotic but anti-calcific bone sialoprotein, regulating tissue. Recognizing OPN mediates processes, hypothesized interstitial cells (VICs) reduced expression...
A collagen-rich tumor microenvironment (TME) is associated with worse outcomes in cancer patients and contributes to drug resistance many types. In melanoma, stiff fibrillar collagen-abundant tissue observed after failure of therapeutic treatments BRAF inhibitors. Increased collagen the TME can affect properties extracellular matrix (ECM), including stiffness, adhesiveness, interaction integrins triple helix forming nanostructures. Decoupling these biochemical biophysical ECM lead a better...
Valve interstitial cells (VIC) are the primary cell type residing within heart valve tissues. In many pathologies, VICs become activated and will subsequently profoundly remodel tissue extracellular matrix (ECM). A indicator of VIC activation is upregulation α--smooth muscle actin (αSMA) fibers, which in turn increase contractility. Thus, contractile state reflects ECM biosynthesis levels. general, contraction studies have largely utilized two--dimensional substrates,which a vastly different...
Enzymatically degradable hydrogels were designed for the 3D culture of valvular interstitial cells (VICs), and through incorporation various functionalities, we aimed to investigate role tissue microenvironment in promoting osteogenic properties VICs matrix mineralization. Specifically, encapsulated a poly(ethylene glycol) hydrogel crosslinked with metalloproteinase (MMP)-degradable crosslinker (KCGPQG↓IWGQCK) formed via thiol-ene photoclick reaction presence or absence collagen type I...
Front Cover: Valvular interstitial cell (VIC) alignment and myofibroblast activation are investigated using a Poly(ethylene glycol) (PEG) based fastrelaxing boronate hydrogel with tunable viscoelasticity. VIC spreading correlates higher extents of stress relaxation, signaling through transient receptor potential vanilloid 4 (TRPV4) calcium channel. A crosstalk between viscoelasticity, signaling, mechanotransduction is proposed, which may provide insights for treatment valvular tissue...
Objective: Recent clinical reports indicate that patients with calcific aortic valve stenosis (AVS) have sexually dimorphic disease phenotypes, where female reduced calcification compared to males. Yet, the cellular mechanisms contributing this dimorphism remain unknown. Our results reveal diseased leaflets from a tend and smaller-scale microcalcifications Additionally, osteopontin (OPN) expression, pro-fibrotic but anti-calcific bone sialoprotein, is elevated in human tissue sections. We...
Objective: Calcific aortic valve disease (CAVD) affects 2.5% of the US population over 75 and there remain no therapeutics, other than surgical replacement, to prevent or reverse progression. The aim this study was better understand role matrix microenvironment in promoting suppressing calcification, specifically with respect that valvular interstitial cells (VICs) play CAVD.Methods: We designed characterized a hydrogel system for 3D VIC culture including proteolytically degradable...