This edition first published 2018
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Library of Congress Cataloging‐in‐Publication Data
Names: Thomson, T. (Tim), author.
Title: Polyurethane immobilization of cells and biomolecules : medical and environmental applications / by T. Thomson.
Description: Hoboken, NJ : John Wiley & Sons, 2018. | Includes bibliographical references and index. |
Identifiers: LCCN 2017036434 (print) | LCCN 2017044756 (ebook) | ISBN 9781119264941 (pdf) | ISBN 9781119264965 (epub) | ISBN 9781119254690 (cloth)
Subjects: LCSH: Immobilized cells. | Polyurethanes–Biotechnology. | Polyurethanes–Industrial applications.
Classification: LCC TP248.25.I55 (ebook) | LCC TP248.25.I55 T56 2018 (print) | DDC 668.4/239–dc23
LC record available at https://lccn.loc.gov/2017036434
Cover design by Wiley
Cover image: Copyright and courtesy of Linda Bradford
In the next several hundred pages, we will be describing a virtual laboratory. The lab has three sections:
Each section will be guided by research on the treatment of recalcitrant pollutants or the development of organ assist devices, specifically the liver and the pancreas. Describing the objectives, plans, and goals of each section is the purpose of this book. Whether the goal is environmental or medical science relater, each section is benefited by the research in the others. We will use research from around the world to show how those concepts can be built into polyurethane chemistry. We will show how the goals of each section are met by a short list of raw materials:
This is not a chemistry book, however. It is the application of chemistry to two of our most important technical challenges, specifically the remediation of polluted air and water and the development of hybrid artificial organs. The later is to meet a permanent shortage of transplantable body parts. While we recognize that these are as different from one another as they can be, we will make the case that the technology to solve one problem is the technology that can solve the other. Consider the human liver. It is a flow‐through device that, among other things, metabolizes components in blood passing through it. Compare this to a tank or column that is packed with a medium to which bacterial cells or enzymes have been immobilized. It is a flow‐through device that metabolizes components in a fluid passing through it. In both cases, there are minimum requirements for the device to function. Among these are permeability and surface area to permit an efficient conversion. These will be explained in detail.
As such, this book is directed toward biotechnologists, specifically whether they are environmental engineers or medical researchers. Having said that, polymer chemists will find it as useful as a comprehensive discussion of a leading edge of polymer technology. Those in the polyurethane industry will see it as a useful extension of this unique polymer chemistry. We will make the case that polyurethane is an ideal chemistry to approach these challenging applications. We will also make the case, probably till you are bored hearing about it, that polyurethane is not a molecule but rather a system composed of several parts, each of which adds to the resultant polymer. For example, it can be hydrophilic or hydrophobic or somewhere in between. It is what we call amicas hydrophilii. Small changes in chemistry allow it to be used as a wound dressing or an automobile fender. The physical forms that polyurethane can take are equally diverse. It can be an elastomer (e.g., for an automobile fender) or a bridge support component. In your local drug store, you can find cosmetic applicator sponges made from polyurethane. Most remarkably, it can be processed such that it is almost not there. Polyurethane sponges can be made with a void volume of 97%. During processing a small amount of water in the formulation changes the resultant polymer from a foam to a hard polymer to an adhesive. We will talk about flow‐through and surface area. These sponges have virtually no resistance to fluids passing through it and with surface areas approaching 7000 m2/m3. The result is a large surface that can be used for a number of applications without inhibiting the flow of fluids. We will be exploring these concepts in detail.
We will describe research done in and for our labs and the research of others in the use of polyurethane and other chemistries as an immobilizing agent for cells and what we call active molecules. Cells include organisms from bacteria to mammalian cells. Active molecules include not only enzymes but also, as we will discuss, cell attachment and other ligands. As we said applications range from not only environmental remediation to clinical but also analytical and diagnostic techniques. We will use the term architecture many times. In the sense of this text, architecture represents a three‐dimensional structure. Not to jump too far ahead of ourselves, but the human liver has a recognizable shape. This is the result of not only cell–cell communication among the cells but also the scaffold within and on which the organ develops.
In probably the most important chapters of the book, we will describe how specific architectures of polyurethanes are made and are then used to support living cells for medical and environmental applications. This identifies the material as a scaffold. That is to say there are many applications for which polyurethanes are used, but when the application is for the support of living cells or biomolecule, we refer to it as a scaffold. This allows us to focus on the applications that are the subject of this book as opposed to the thousands of uses for this unique polymer system.
For the biotechnologists, let us warn you that we are chemists. What we know of the subject we will be discussing is based on work we have done with professionals and from the literature. We have sponsored research at various labs and universities, and although we cannot call ourselves expert, we are confident that the technology herein described is real and valuable.
To begin the discussion, it is necessary to describe chemistry. Don’t be concerned. While the discussion is comprehensive, it is not complicated. The first chapter is a graduate‐level course in polyurethane but only requires introductory knowledge of general chemistry. As we will discuss, polyurethanes have several parts, each of which influence the characteristics of the resultant polymer. At the end of the chemistry chapter, you will begin to know what parts might meet your individual requirements. Then the information in the chapters on controlled release and immobilization will complete your education.
Having said that, there are several companies that make the raw materials for your research. Therefore, while your research might eventually design your own polymers, it is convenient to begin with commercial materials. As you develop skills in the techniques, and even develop novel techniques, you may have a need to make adjustments in the basic chemistry. For example, you may need a stiffer material or more flexible. Polyurethanes offer a convenient way of making those changes. More appropriately, we will be discussing biodegradability and biocompatibility, both of which are far from being resolved. Regardless of your training we would advise you to go through chemistry in order to see the context with the rest of the book.
By way of introduction, we were part of the hydrophilic polyurethane (HPUR) commercial venture at the W. R. Grace Corp. The trade name for the family of products was Hypol™ prepolymer, still the dominant producer of HPUR products. I was assigned to support the existing sales base and expand the applications. In the several years I spent in that position, I had the pleasure to travel the world explaining the benefits of this unique chemistry. The product markets ranged from personal care products to advanced medical devices to agriculture. After leaving Grace, I organized Main Street Technologies as a venue for my personal research interests, writing several books, and limited consulting. During that period we took several assignments in manufacturing units. This expanded my knowledge of polyurethanes with day‐to‐day experience in the manufacture of foam. We always maintained a research focus, however.
While the metaphor of “standing on the shoulders of giants” is commonly used, I refer to my career as that of a student. The men I have worked with and for, and the customers that I tried to help, have been my teachers. I have taken what has been taught to me and applied it to my own research. I can only hope that I have earned a passing grade. In any case, this book is in part dedicated to them. More important than that I dedicate this book to my wife, Maguy. Her love helped me from a wild eye kid to something resembling a scientist.
This book is unique in a sense in that it speaks to two audiences, typically considered sufficiently different to be considered other sciences. We work in both areas without confusion, but in an effort to speak to both audiences simultaneously, we must rigorously avoid jargon. Those of you who have tried to be technical generalists will understand the difficulty in walking that line. As an example of what we need to avoid, consider the following:
“this spiral arrangement of collagen fibers with their adjacent smooth muscle cell layer allows the small intestines to constrict in a manner that promotes the efficient transport of a bolus of biomass.”
Most of us know this process by other names.
Lastly, when you as an environmentalist read the sections on medical research, when they say blood, mentally transpose that into air or water. It will make perfect sense. Conversely, as medical professionals, when reading about environmental issues, replace references to air and water to blood. You will see the continuity.
We were asked by a New York artist to help her find a replacement for a brush that she had used to create the effect seen on the cover. For whatever reason, she was not able to find replacement brushes, and so she was not able to duplicate her innovative technique. To make a long story short, we determined that the effect was due to a number of factors. Pore structure, size, and architecture, which control the flow, were the most important. We also found that surface chemistry (wetting) and chemistry of the paints were critical.
As you go through this text, you will see that these sane properties will be mentioned over and over again as we develop our arguments. We, therefore, thought it would be appropriate.