Megan C Frost

The development of an ideal vascular prosthesis represents an important challenge in terms of the treatment of cardiovascular diseases with respect to which new materials are being considered that have produced promising results following testing in animal models. This study focuses on nanofibrous polycaprolactone-based grafts assessed by means of...

Orthodontic treatment commonly requires the need to prevent movement of some teeth while maximizing movement of other teeth. This study aimed to investigate the influence of locally injected nitric oxide (NO) releasing nanoparticles on orthodontic tooth movement in rats. Materials and methods: Experimental tooth movement was achieved with nickel-...

Constant or intense light degenerates the retina and retinal pigment epithelial cells. Light generates reactive oxygen species and nitric oxide leading to initial reactions of retinal degeneration. Apoptosis is the primary mechanism of abnormal death of photoreceptors, retinal ganglion cells, or retinal pigment epithelium (RPE) in degenerative reti...

Synthetic nitric oxide (NO)-donating materials have been shown to have many beneficial effects when incorporated into biomedical materials. When released in the correct dosage, NO has been shown to increase the biocompatibility of blood and tissue contacting materials, but materials are often limited in the amount of NO that can be administered ove...

Diabetic foot ulcers (DFU) are a major health problem associated with diabetes mellitus. Impaired nitric oxide (NO) production has been shown to be a major contributor to the dysregulation of healing in DFU. The level of impairment is not known primarily due to challenges with measuring NO. Herein, we report the actual level of NO produced by human...

Diabetic foot ulcers (DFUs) are the leading cause of lower extremity amputation in the United States, and the prognosis after an initial amputation is fairly grim. Many advanced wound healing therapies are currently available for the treatment of DFUs, including growth factor therapy, bioengineered skin substitutes, and autologous platelet solution...

Microgels that can generate antipathogenic levels of hydrogen peroxide (H2O2) through simple rehydration in solutions with physiological pH are described herein. H2O2 is a widely used disinfectant but the oxidant is hazardous to store and transport. Catechol, an adhesive moiety found in mussel adhesive proteins, was incorporated into microgels, whi...

Polyvinyl chloride (PVC) is one of the most widely used polymers in medicine but has very poor biocompatibility when in contact with tissue or blood. To increase biocompatibility, controlled release of nitric oxide (NO) can be utilized to mitigate and reduce the inflammatory response. A synthetic route is described where PVC is aminated to a specif...

The gold standard of care for coronary artery disease, a leading cause of death for in the world, is balloon angioplasty in conjunction with stent deployment. However, implantation injuries and long‐term presence of foreign material often promotes significant luminal tissue growth, leading to a narrowing of the artery and severely restricted blood...

Directly monitoring physiological analytes on a continuous, real-time basis may lead to improved patient outcomes. Although the technology to fabricate robust miniature sensors has existed for decades, these sensors fail to accurately track the true physiological status of patients after implantation in the human body. Nitric oxide (NO) may be empl...

The antibacterial effect of zinc oxide (ZnO#1) as prepared and annealed (ZnO#2) at 400 °C, Cu doped ZnO (CuZnO), and Ag doped ZnO (AgZnO) nanoplates on Staphylococcus epidermidis was investigated for the inhibition and inactivation of cell growth. The results shows that pure ZnO and doped ZnO samples exhibited antibacterial activity against Staphyl...

Applying soluble nitric oxide (NO) donors is the most widely used method to expose cells of interest to exogenous NO. Because of the complex equilibria that exists between components in culture media, the donor compound and NO itself, it is very challenging to predict the dose and duration of NO cells actually experience. To determine the actual le...

Nitric oxide (NO), identified over the last several decades in many physiological processes and pathways as both a beneficial and detrimental signaling molecule, has been the subject of extensive research. Physiologically, NO is transported by a class of donors known as S-nitrosothiols. Both endogenous and synthetic S-nitrosothiols have been report...

Nitric oxide (NO), is arguably one of the most important small signaling molecules in biological systems. It regulates various biological responses in both physiological and pathological conditions, often time producing seemingly contradictory results. The details of the effects of NO are highly dependent on the level of NO that cells experience an...

Nitric oxide (NO) has been heavily studied over the past two decades due to its multitude of physiological functions and its potential therapeutic promise. Of major interest is the desire to fabricate or coat implanted devices with an NO releasing material that will impart the appropriate dose and duration of NO release to positively mediate the bi...

Although significant advances have been made in the development of artificial vascular grafts, small-diameter grafts still suffer from excessive platelet activation, thrombus formation, smooth muscle cell intimal hyperplasia, and high occurrences of restenosis. Recent discoveries demonstrating the excellent blood-contacting properties of the natura...

We review approaches and challenges in developing chemical sensor-based methods to accurately and continuously monitor levels of key analytes in blood related directly to the status of critically ill hospitalized patients. Electrochemical and optical sensor-based technologies have been pursued to measure important critical care species in blood [i....

The usage of gelatin hydrogel is limited due to its instability and poor mechanical properties, especially under physiological conditions. Divalent metal ions present in gelatin such as Ca(2+) and Fe(2+) play important roles in the gelatin molecule interactions. The objective of this study was to determine the impact of divalent ion removal on the...

Nitric oxide (NO) is an ubiquitous signaling molecule of intense interest in many physiological processes. Nitric oxide is a highly reactive free radical gas that is difficult to deliver with precise control over the level and timing that cells actually experience. We describe and characterize a device that allows tunable fluxes and patterns of NO...

Light is a risk factor for various eye diseases, includ-ing age-related macular degeneration (AMD) and retinitis pigmentosa (RP). We aim to understand how cytoskeletal proteins in the retinal pigment epithet-lium (RPE) respond to oxidative stress, including light and how these responses affect apoptotic signal-ing. Previously, proteomic analysis re...

There are many remaining challenges impeding future progress in field of Clinical Diagnostics. This book presents a technical assessment and vision of clinical leaders, scoping the clinical and other diagnostic needs and the bottle-necks in their cognate fields. Issues of real environmental biological measurements from the perspective of the end-us...

Nitric oxide plays important roles in cardiovascular homeostasis, immune responses and wound repair. Therefore, polymers that release nitric oxide locally at the surface exhibit improved biocompatibility for biomedical implants through reducing neointimal hyperplasia and thrombosis caused by blood vessel wall damage. The objective of this article w...

An S-nitroso-N-acetylpenicillamine (SNAP) derivatization approach was used to modify existing free primary amines found in fibrin (a natural protein-based biomaterial) to generate a controlled nitric oxide (NO) releasing scaffold material. The duration of the derivatization reaction affects the NO release kinetics, the induction of controlled NO-re...

Nitric oxide (NO) plays an important role in cardiovascular homeostasis, immune responses, and wound repair. The pro-angiogenic and antimicrobial properties of NO has stimulated the development of NO-releasing materials for wound dressings. Gelatin, an abundant natural biodegradable polymer derived from collagen, is able to promote wound repair. S-...

Nitric oxide (NO) release can promote healthy tissue regeneration. A PEG-fibrinogen adhesive hydrogel that would allow for inducible NO release was created with mechanical properties that could be tailored to specific applications and tissue types. PEG (4-arm)-fibrinogen hydrogels of varying ratios were derivatized with S-nitroso-N-acetyl-D, L-peni...

Light is a risk factor for various eye diseases, includ-ing age-related macular degeneration (AMD) and retinitis pigmentosa (RP). We aim to understand how cytoskeletal proteins in the retinal pigment epithet-lium (RPE) respond to oxidative stress, including light and how these responses affect apoptotic signal-ing. Previously, proteomic analysis re...

Despite the documented potential to leverage nitric oxide generation to improve in vivo performance of implanted devices, a key limitation to current NO releasing materials tested thus far is that there has not been a means to modulate the level of NO release after it has been initiated. We report the fabrication of a wireless platform that uses li...

Nitric oxide (NO) has shown to play important and diverse biological roles. NO is suspected to be beneficial at low levels for a variety of cells, including retinal epithelial cells, lymphatic epithelial cells, and dorsal root ganglion cells, but can be detrimental at high levels or at certain periods of time in their growth. Currently, the benefic...

Nitric oxide (NO) plays a critical role in the regulation of a wide variety of physiological processes. It is a potent inhibitor of platelet adhesion and aggregation, inhibits bacterial adhesion and proliferation, is implicated in mediating the inflammatory response toward implanted devices, plays a role in tumor growth and proliferation, and is a...

Nitric oxide (NO) plays an important role in inhibiting the development of hepatic fibrosis and its ensuing complication of portal hypertension by inhibiting human hepatic stellate cell (HSC) activation. Here we have developed a gold nanoparticle and silica nanoparticle mediated drug delivery system containing NO donors, which could be used for pot...

Measuring the blood gases of patients in the intensive care unit or undergoing major surgical procedures in real time would help healthcare providers diagnose and manage base excess and base deficient disorders. Optical fibers provide a platform upon which an intravascular blood gas sensor may be built and has been by various companies. Unfortunate...

Previous studies have shown that many S-nitrosothiols (RSNOs) rapidly degrade, with half-lives from minutes to seconds in aqueous solution [1]. The research presented in this paper presents data that the RSNO 1,3-benzenedinitrosothiol has been relatively stable for over 1 year. This RSNO still releases nitric oxide (NO) when subjected to ultraviole...

Biomedical devices that contact blood and tissue universally inspire a host response that often compromises the function of the device (i.e., intravascular sensors become coated with thrombi, artificial vascular grafts become coated with thrombi, artificial vascular grafts become occluded with thrombus formation and neointimal hyperplasia). Nitric...

Nitric Oxide (NO) is small, free radical gas that has been shown to have a wide variety of physiological functions, including the ability to hinder tumor angiogenesis at high, but non lethal, concentrations [1]. Previous work suggests that if NO could be effectively delivered in vivo to tumors of patients currently undergoing chemotherapy treatment...

Nitric Oxide (NO) is small, free radical gas that has been shown to have a wide variety of physiological functions, including the ability to hinder tumor angiogenesis at high, but non lethal, concentrations. Previous work suggests that if NO could be effectively delivered in vivo to tumors of patients currently undergoing chemotherapy treatments at...

Biomedical devices that contact blood and tissue universally inspire a host response that often compromises the function of the device (i.e., intravascular sensors become coated with thrombi, artificial vascular grafts become occluded with thrombus formation and neointimal hyperplasia). Nitric oxide (NO) has been shown to be a potent inhibitor of p...

The gold standard for anticoagulation during extracorporeal circulation (ECC) remains systemic heparinization and the concomitant risk of bleeding in an already critically ill patient could lead to death. Normal endothelium is a unique surface that prevents thrombosis by the release of antiplatelet and antithrombin agents. Nitric oxide (NO) is one...

Because of the biological response of the host, an implanted medical device may not report the true or diagnostically relevant level of the analyte in the patient's blood. Megan Frost and Mark E. Meyerhoff of the University of Michigan discuss the issues of trying to make reliable measurements with sensors implanted intravascularly and subcutaneous...

The current state-of-the-art with respect to the preparation, characterization and biomedical applications of novel nitric oxide (NO) releasing or generating polymeric materials is reviewed. Such materials show exceptional promise as coatings to prepare a new generation of medical devices with superior biocompatiblity. Nitric oxide is a well-known...

A new type of nitric oxide (NO)-releasing material is described that utilizes S-nitrosothiols anchored to tiny fumed silica (FS) particles as the NO donor system. The synthetic procedures suitable for tethering three different thiol species (cysteine, N-acetylcysteine, and N-acetylpenicillamine) to the surface of FS polymer filler particles are det...

The synthetic methods used recently in this laboratory to prepare a variety of novel nitric oxide (NO)-releasing hydrophobic polymers are reviewed. Nitric oxide is a well known inhibitor of platelet adhesion and activation. Thus, such NO release polymers have potential applications as thromboresistant coatings for a large number of blood-contacting...

This report describes the first hydrophobic nitric oxide (NO)-releasing material that utilizes light as an external on/off trigger to control the flux of NO generated from cured polymer films. Fumed silica polymer filler particles were derivatized with S-nitroso-N-acetyl-dl-penicillamine and blended into the center layer of trilayer silicone rubber...

This chapter describes the procedure employed to construct functional NO-releasing catheter-type amperometric oxygen sensors, including coating the sensor with NO-release materials, assembly of the sensor itself, and in vivo evaluation of the analytical performance and hemocompatibility of the device. The procedure describing the specific fabricati...

The widespread use of miniaturized chemical sensors to monitor clinically important analytes such as PO2, PCO2, pH, electrolytes, glucose and lactate in a continuous, real-time manner has been seriously hindered by the erratic analytical results often obtained when such devices are implanted in vivo. One major factor that has influenced the analyti...

The in vivo biocompatibility and analytical performance of amperometric oxygen-sensing catheters prepared with a new type of nitric oxide (NO)-releasing silicone rubber polymer (DACA/N2O2 SR) is reported. The NO-release silicone rubber coating contains diazeniumdiolated secondary amine sites covalently anchored to a dimethylsiloxane matrix. Narrow...

The in vitro analytical performance of fluorescence-based oxygen sensing polymeric films prepared with silicone rubbers that spontaneously release nitric oxide (NO) is examined. The use of NO-release polymers for fabricating functional optical sensors is proposed as a potential solution to fingering biocompatibility and concomitant performance prob...

Recently, progress has been made in the development of implantable chemical sensors capable of real-time monitoring of clinically important species such as PO(2), PCO(2), pH, glucose and lactate. The need for developing truly biocompatible materials for sensor fabrication remains the most significant challenge for achieving robust and reliable sens...

A synthetic path for the preparation of methacrylic homo- and copolymers containing secondary amine groups that can be converted into nitric oxide (NO) releasing N-diazeniumdiolates is described. The polymers are obtained by a multistep procedure involving synthesis of methacrylate monomers containing boc-protected secondary amine sites, free radic...

Planar chromatography with electroosmotic flow is used to separate either a mixture of dyes using 80% aqueous ethanol as the mobile phase or a mixture of miscellaneous compounds using 45% aqueous acetonitrile as the mobile phase. Both mobile phases are 1.0 mM in N-[tris(hydroxymethyl)methyl]-3-aminopropanesulfonic acid (TAPS) buffer. Separations us...

We have used multiple linear regression to predict either initial rate, log initial rate or specificity for enzyme-catalyzed reactions performed in non-aqueous solvents. The Subtilisin Carlsberg catalyzed transesterification of N-acetyl-l-phenylalanine ethyl ester by methanol, 1-propanol, and 1-butanol was assayed in 30 non-aqueous solvents, and th...

The p-nitrobenzyl ester of the dansyl derivatives of fifteen amino acids were prepared and chromatographed on silica gel plates using a series of single-solvent mobile phases. Multiple linear regression was used to construct a model that predicts retention as a function of the polar surface area and the nonpolar surface area of each solvent. The va...

A mixture of dyes has been separated by planar chromatography using electroosmotic flow. Separation is faster and peak shape is better than that obtained by conventional planar chromatography. When using a potential of 3.0 kV a mobile phase flow of 2 cm min-1 was observed during the early part of the development, but this diminishes as the separati...

Either a second order or a third polynomial equation accurately predicts RF in a mobile phase which is a binary mixture of a strong and weak solvent. The mole fraction of the strong solvent is used as the independent variable. The p-nitrobenzyl esters of fifteen dansyl amino acids were used as model solutes for planar chromatography, using each of...

Dissertation (Ph.D.)--University of Michigan.