Polyurethane Immobilization of Cells and Biomolecules - T. Thomson - ebook

Polyurethane Immobilization of Cells and Biomolecules ebook

T. Thomson

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This book provides a comprehensive review of the chemistry and research illustrating the benefits of polyurethane for immobilizing cells, with dozens of case studies in medical devices and environmental engineering. * Offers an essential resource for medical and environmental scientists * Provides a multidisciplinary and lucid writing style that uses little or no jargon * Extrapolates current technology into advanced areas, especially environmental remediation and medical devices * Fills the gap between immobilization research and practical applications

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Table of Contents

Cover

Title Page

Preface

Cover Art

1 Polyurethane Chemistry

Introduction

The Chemistry

The Water Reaction

Process

Biodegradable PUR

Conclusion

References

2 Laboratory Practice

Introduction

Prepolymers

Hydrophilic Foams

Custom Prepolymers, Foams, and Scaffolds

Examples

Structure–Property Relationships

The Special Case of Hydrophilic Polyurethane Foams

Physical and Chemical Testing

Biocompatibility Testing

Process Equipment

References

3 Scaffolds

Introduction

Bioscaffolds

Scaffolds for Medical Applications (

In Vivo

and Extracorporeal

)

The Liver Model

The Extracellular Matrix as Scaffold

The Physical Scaffold

Design of an Ideal Scaffold

Drug Discovery

Materials of Construction

The “Ideal” Scaffold

Specifications of the Ideal Scaffold

References

4 Immobilization

Introduction

Methods of Immobilization

Immobilization by Adsorption

Protein Adsorption

Immobilization by Extraction

Immobilization by Entrapment

Summary of Encapsulation

Immobilization by Covalent Bonding

Summary

Polyurethane Immobilization

Preparation of Immobilized Biomolecules

Notable Uses of Polyurethane for Immobilization

Conclusion to Immobilization

References

5 Controlled Release from a Hydrogel Scaffold

Introduction

Release Rates

Examples of Hydrogels Used for Controlled Release

Controlled Release by Diffusion

Islet Encapsulation

Other Controlled Release Examples

Summary and Conclusions

References

Index

End User License Agreement

List of Tables

Chapter 01

Table 1.1 Effect of functionality.

Table 1.2 Component list for a conventional polyurethane by the one‐shot process.

Table 1.3 Typical properties of a commercial reticulated.

Chapter 02

Table 2.1 Commercially available open‐cell foam producing prepolymers.

Table 2.2 Reactivity of parts A and B.

Table 2.3 Typical values from a commercial prepolymer.

Table 2.4 Formulation for prepolymer preparation.

Table 2.5 Properties of the resultant foam.

Table 2.6 Formulary of the Wu study.

Table 2.7 Experimental grid of spinal disc study.

Table 2.8 Results of the spinal disc project.

Table 2.9 Samples for compression tests.

Table 2.10 Molar cohesive energy of organic groups.

Table 2.11 Control of cell size using surfactants.

Chapter 03

Table 3.1 Surface area of common scaffold materials.

Table 3.2 Range of pore sizes within a pore size grade.

Table 3.3 Tobacco plant biofilter.

Table 3.4 Hydrocarbon removal.

Table 3.5 The liver as biofilter.

Table 3.6 The compressive strength of HA/Col composite scaffold.

Table 3.7 Analysis of foam.

Table 3.8 Analysis of the foams.

Table 3.9 Cells immobilized on polyurethane.

Tables 3.10 The physical of our ideal scaffold.

Chapter 04

Table 4.1 Types of immobilization.

Table 4.2 Biofilter characteristics at start‐up (unpublished data).

Table 4.3 Various studies on the removal of toluene (information is part of an unpublished research).

Table 4.4 Schedule of samples for inoculation.

Table 4.5 Pluronic and other surfactants.

Table 4.6 Colorimetric determination of explosives.

Table 4.7 List of Ingredience in example 1.

Table 4.8 US pesticide market

by function and volume, 2007.

Table 4.9 Persistence of organophosphate

pesticides.

Table 4.10 Foam for lipase study.

List of Illustrations

Chapter 01

Figure 1.1 The urethane reaction.

Figure 1.2 The aromatic diisocyanates.

Figure 1.3 Aliphatic diisocyanates

(top is hydrogenated MDI, below is isopherone diisocyanate

).

Figure 1.4 Polyester polyols.

Figure 1.5 Polyether polyols.

Figure 1.6 The reaction of isocyanates with water.

Figure 1.7 The reaction of isocyanates with amines (urea linkage).

Figure 1.8 An impingement mixer.

Figure 1.9 The foaming process

after leaving the mix head.

Figure 1.10 The prepolymer reaction (the triol is not shown for clarity).

Figure 1.11 Micrograph of an open‐cell foam.

Figure 1.12 Typical reticulated foam.

Figure 1.13 Two spheres approaching one another.

Figure 1.14 Lowest surface energy among two cells.

Figure 1.15 Foam architecture.

Figure 1.16 Coating process for the hydrophilic polyurethane composite.

Figure 1.17 Micrograph of the composite with a coating weight of 25% hydrophilic PUR.

Figure 1.18 Isocyanates appropriate for biodegradable polyurethanes.

Figure 1.19 Polyols appropriate for biodegradable polyurethanes.

Figure 1.20

In vivo

degradation of polyurethanes.

Chapter 02

Figure 2.1 The prepolymer reaction.

Figure 2.2 Typical viscosity increases as a function of time.

Figure 2.3 Effect of chemistry on platelet adhesion.

Figure 2.4 Compression of a synthetic nucleus.

Figure 2.5 Apparatus for determining airflow through.

Figure 2.6 Recycle to prevent dead heading.

Chapter 03

Figure 3.1 Surface area by pore size of a reticulated foam.

Figure 3.2 Bioscaffold decision tree.

Figure 3.3 Adhesion of osteoblasts to the chitosan/PU scaffolds.

Figure 3.4 Estimate of cell diameter calculated as a dodecahedron.

Figure 3.5 Flow sheet of the process to make ceramic foam.

Figure 3.6 Micrographs of unfilled (a) and filled (b) foams before pyrolysis.

Figure 3.7 A tetrakaidecahedron compared with a reticulated polyurethane.

Figure 3.8 Effect of pyrolysis on ceramic‐filled foam. Arrow indicates window in the unfired foam.

Figure 3.9 Pressure drop across a scaffold.

Figure 3.10 Pressure drop across a scaffold at 200 fpm.

Figure 3.11 Idealized stress–strain curves (tensile on the left, compression on the right).

Figure 3.12 An idealized scaffold.

Chapter 04

Figure 4.1 Adsorption to a surface.

Figure 4.2 Coating process preparation of a composite foam.

Figure 4.3 Biofilter setup for toluene (left) and hydrogen sulfide.

Figure 4.4 Pressure drop through composite foam.

Figure 4.5 Start‐up of toluene bioreactor.

Figure 4.6 Comparison of the performance of the modified composite foam (▴) and the Zander (+) foam.

Figure 4.7 Removal of H

2

S.

Figure 4.8 Effect of EBRT (unpublished data).

Figure 4.9 Performance of the H

2

S bioreactor.

Figure 4.10 University of Maine Aquarium study.

Figure 4.11 Biotin.

Figure 4.12 Adhesion of chondrocytes.

Figure 4.13 The macro‐ and microstructures of the TCP scaffolds.

Figure 4.14 Results of cell growth.

Figure 4.15 Albumin production of Hep G2 cells in the polycaprolactam scaffold.

Figure 4.16 Immobilization by extraction.

Figure 4.17 Glycols used for biphasic separations.

Figure 4.18 Improved absorption of oil by a derivatized polyurethane foam (left).

Figure 4.19 Extraction of pesticides.

Figure 4.20 Transmission of an organic dye with hydrophobic polyurethane.

Figure 4.21 Extraction of an organic dye with a hydrophilic polyurethane.

Figure 4.22 Extraction of a dye using hydrophilic polyurethane.

Figure 4.23 Rotational spectroscopy using a fiber optics.

Figure 4.24 Rotational spectroscopy of various color coupons (B, blue; R, red; O, orange; W, white).

Figure 4.25 Extraction of “bathroom odors” by molecular weight.

Figure 4.26 Extraction of essential oils from the air.

Figure 4.27 Immobilization by entrapment.

Figure 4.28 Insulin release from islets encapsulated in PEG gels.

Figure 4.29 Comparison of hepatic (left) and islet spheroids cultured in a 3D environment.

Figure 4.30 Hepatic spheroid cultured in a reticulated polyurethane foam (100 µm).

Figure 4.31 Covalent bond to a scaffold.

Figure 4.32 Activation of cellulose.

Figure 4.33 MMA grafting and activation of PLLA.

Figure 4.34 Colonized MMA‐graphed PLLA scaffold.

Figure 4.35 Open‐cell foam.

Figure 4.36 The prepolymer reaction.

Figure 4.37 The water reaction.

Figure 4.38 The amine reaction.

Figure 4.39 Reactions of isocyanates (R─N═C═O) with enzyme surfaces.

Figure 4.40 NIH/3T3 cell attached to the fibronectin‐imbibed scaffold (left 48 h right 96 h) (unpublished data).

Figure 4.41 Cell growth of smooth muscles by composite scaffold by pretreatment.

Figure 4.42 Hepatic spheroid cultured in a reticulated polyurethane foam (scale = 100 µm).

Figure 4.43 Gion

et al

. multicapillary system.

Chapter 05

Figure 5.1 A segment of a scaffold pore showing a reservoir layer and the biocompatible surface.

Figure 5.2 Comparison of injection and a controlled release device for insulin.

Figure 5.3 Rates of controlled release.

Figure 5.4 Migration of the solute from a reservoir into an identical membrane.

Figure 5.5 Migration of a solute from a reservoir into a membrane with a lower diffusion coefficient.

Figure 5.6 Diffusion coefficient as a function of molecular size.

Figure 5.7 Volumetric swelling in serum (Ref. [5]).

Figure 5.8 Diffusion coefficient as a function of the molecular weight of the PEG.

Figure 5.9 Relationship of the diffusion coefficient and the hydrodynamic radius.

Figure 5.10 Insulin release from islets encapsulated in PEG gels.

Figure 5.11 Diffusion of cytochrome and hemoglobin in PEO hydrogels.

Guide

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Polyurethane Immobilization of Cells and Biomolecules

Medical and Environmental Applications

T. Thomson

This edition first published 2018© 2018 John Wiley & Sons, Inc.

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.

The right of T. Thomson to be identified as the author of this work has been asserted in accordance with law.

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Limit of Liability/Disclaimer of WarrantyIn view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of experimental reagents, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each chemical, piece of equipment, reagent, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. While the publisher and authors have used their best efforts in preparing this work, they make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives, written sales materials or promotional statements for this work. The fact that an organization, website, or product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors endorse the information or services the organization, website, or product may provide or recommendations it may make. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for your situation. You should consult with a specialist where appropriate. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.

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–dc23LC record available at https://lccn.loc.gov/2017036434

Cover design by WileyCover image: Copyright and courtesy of Linda Bradford

Preface

In the next several hundred pages, we will be describing a virtual laboratory. The lab has three sections:

Scaffold development

Immobilization technologies

Controlled release

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:

A commercially reticulated polyurethane foam

Polyethylene glycol (1000, 4000, and 10 000 molecular weights)

Toluene diisocyanate

Trimethylolpropane

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.

Cover Art

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.

1Polyurethane Chemistry

Introduction

There are many texts on polyurethanes (PURs) but this one has a special interest. After the first couple of chapters, we will focus on how this chemistry can be used to advance the sciences of environmental remediation and medical science. While those may seem too diverse for a single volume, we think we can make the case that there is a unifying aspect, and, furthermore, it is PURs that best fit that role. Polyurethanes are remarkable in the world of polymers in that they are not a molecule like polyethylene or polyvinylchloride, but rather a system with multiple component parts. Each of those parts fulfills a certain and individual function. It is their selection and the methods used to process the polymer that make it unique. With the help of this book, a scientist with ordinary knowledge of chemistry can learn these techniques. Furthermore, unlike the more common polymers, innovative research can be developed in the average laboratory setting. Among other things, you will learn how to make products from elastomers to foams to adhesives with only slight changes in chemistry or processes. Applying those simple skills with the experience taught in the final chapters, the reader is offered the potential to conduct world‐class research in fields from water and air treatment to artificial organs. A bold claim, but defendable.

To begin, PURs are a family of polymers all based on the reaction of an organic isocyanate and a multifunctional polymer. Isocyanates, as we will discuss, react quickly with other compounds like water, amines, alcohols, and organic acids. The defining aspect of a PUR is the isocyanate starting material. Because of its somewhat unique reactivity, one can build a polymer of his or her own design. It is what you react the isocyanate with that defines the characteristic of the resultant PUR. For example, with the same isocyanate one can produce a hydrophobic or hydrophilic foam and a seat cushion or a dressing to treat dermal ulcers. As this book develops we hope to illustrate the range of products and technologies that are possible with the knowledge taught in this chapter and the talents of the reader.

As we mentioned, PURs are a combination of several parts. We will describe each of these but a history lesson is appropriate. The first official PURs were developed prior to World War II. It was first produced as a replacement for natural rubber. Otto Bayer and his coworkers at I.G. Farben in Leverkusen, Germany, made PURs in 1937. The first PURs were hydrophilic. Their intended use was for automobile tires, but the polymers were not strong enough to withstand the weight of a car when wet. It wasn’t until hydrophobic polyols were used that it became the useful material we know today. It was in the 1950s that Monsanto developed the so‐called “one‐step” process to make foam that made PURs economically viable in a wide range of product markets. The campaign to reduce weight and cost catalyzed the expansion of PUR elastomers in automobile parts. Currently, applications range from furniture foams to elastomers to adhesives for home and industrial use. We remind you that this has happened without major changes in the chemistry. In the 1970s a hydrophilic version was redeveloped and numerous unique applications researched, including the immobilization of biomolecules and cells. This research led to the international hydrophilic PUR industry. It is our opinion that this product and derivatives thereof will provide a path into expanded medical and environmental uses.

The Chemistry

Commercial PURs are the result of the exothermal reaction between an isocyanate and a molecule containing two or more alcohol groups (–OH). While this defines current commercial applications, the chemistry is not limited to alcohols, as we will explain. The properties of the resultant PUR depend on the choice of these components. If the application is as a consumer product, both cost and strength of materials guide the development and so appropriate components are selected. If the product is to be biocompatible or come into contact with blood, a different set of components will be necessary and cost may not be a critical factor.

In either case, Figure 1.1 shows the reaction of an isocyanate and an alcohol. The result illustrates the urethane linkage. One can imagine the polymerization using a diisocyanate and molecules with multiple –OH end groups.

Figure 1.1 The urethane reaction.

There are many isocyanates and polyols to choose from and these are the tools of the trade to a urethane chemist. While we will see that there is a limited supply when it comes to the choices of isocyanate, there is no limit to possible reactants. We will explore this in detail when we focus particularly on medical products. In that discussion we will report on research that uses modified polypeptides as replacements for conventional polyols. For clarity, what “R” represents is the subject of much research around the world.

To investigate this further, we will look at the components in more detail.

The Isocyanates

The world of commercial PURs is predominantly split between two isocyanates: toluene diisocyanate (TDI) and methylene‐bis‐diphenyldiisocyanate (MDI). Both of these are considered “aromatic” as they are built around the benzene ring. This has product shelf‐life implications (Figure 1.2).

Figure 1.2 The aromatic diisocyanates.

Their relative importance depends on a number of factors. TDI was the first successful isocyanate and is still important. It is relatively inexpensive, and due in part to its molecular weight (MW), the properties of the PUR from which it is made are more sensitive to the polyol.

We will be using a convention when describing polymers of this type. The isocyanate portion of a polymer is said to be a “hard” segment due to its MW and inability of the molecule to rotate within itself. The polyol, however, is a longer molecule and has a high degree of internal rotation. It is, therefore, referred to as “soft.” Thus a polymer with a higher mass percent of isocyanate would tend to be stiffer/harder, and vice versa.

Polymers made from TDI are generally softer because of the relative weights of isocyanate and polyol, which is the preferred isocyanate for hydrophilic PURs. The higher percentage of polyol makes for more hydrophilic foam as well.

The bulk of the conventional PUR business, however, has shifted toward MDI as the isocyanate of choice. MDI is sold in different forms. In any case, its higher MW means that it is a portion of the resultant polymer with a higher weight. This makes it “harder” and more hydrophobic. This has strong implications for product characteristics. There are hydrophilics based on MDI but they tend to make more “boardy” foams due, in part, again to its increased mass % in the urethane molecule.

While the so‐called aromatics (TDI and MDI) represent the dominate isocyanates in the conventional and hydrophilic PUR businesses, they have a problem with respect to weathering, specifically yellowing on exposure to light and heat. While this may seem to be insignificant, the aesthetics of a product made from these materials is typically important. Whether the device is a cosmetic applicator or a wound dressing, yellowing is typically viewed as a degradation of the usefulness of the product. There is no evidence that the physical or hydrodynamic properties are affected by normal yellowing, but it is almost always an issue.

Three processes cause the yellowing. Exposure to UV light causes the production of color bodies in aromatic isocyanates (TDI, MDI, etc.). This can be inhibited by the use of UV‐absorbing compounds. Most commonly, however, is to use packaging that is opaque to the ultraviolet.

Another major cause of yellowing is heat. Temperatures above 105°C can noticeably yellow foam in a few minutes. Ring opening and the resultant conjugated structures are thought to be the cause.

Lastly, exposure to hydrocarbon emissions causes yellowing. For this reason, hydrophilic PUR foam manufacturers typically use electric forklift trucks. As we will explain in the chapter on immobilization, PURs have a unique ability to absorb hydrocarbons from the air due to the polyol part of the molecule, which, again as we will discuss, is well known as a solvent extraction medium.

When the yellowing has to be eliminated (as opposed to inhibited), other isocyanates are available. The most common are the aliphatics shown in Figure 1.3.

Figure 1.3 Aliphatic diisocyanates (top is hydrogenated MDI, below is isopherone diisocyanate).

You will notice that these compounds still have the six‐member ring component, but, in this case, the ring is cyclohexane. It does not absorb UV of sufficient energy to produce the yellowing effect observed with TDI and MDI.

The Polyol

For the most part, the polyol gives the PUR its chemical nature, especially when TDI is the isocyanate inasmuch as the polyol is the major constituent. The secret to making even softer foams is to change the length of the polyol chain.

Two types of polyols are typically used, polyesters and polyethers. The polyesters are usually based on adipic acid, but others are available. The polyethers are derivatives of ethylene and propylene oxides.

The following is a typical polyester (Figure 1.4):

Figure 1.4 Polyester polyols.

These are essentially hydrophobic chemicals and therefore lead to hydrophobic PURs. The structure of the polyethers is as follows (Figure 1.5):

Figure 1.5 Polyether polyols.

Polypropylene glycol (left) is essentially hydrophobic, while polyethylene glycol is hydrophilic and is the basis for the hydrophilic PUR business.

The propylene‐based polyols (left of Figure 1.5) are currently the basis of most conventional PURs. The methylene group on the polypropylene molecule (at useful MWs) renders it hydrophobic. Contrast this to the polyethylene glycol (right of Figure 1.5), which is water soluble at high MWs. As we said, it is the polyol of choice for most hydrophilic PURs. Both polyols are available in several MWs and the number of –OH groups. This gives the researcher multiple degrees of freedom.

In current practice, foam manufacturers prefer polyethers for the following reasons:

Lower cost

Better hydrolytic stability

Mechanical flexibility

Cross‐Linking

Cross‐linking is used to control many of the mechanical properties of the final product. Trifunctional alcohols are used for this purpose but any molecule that has more than two reactive sites will do. Cross‐linkers for this discussion are typically another polyol. The polyols we have discussed are alternatively called alcohol‐capped polyols but in fact they are diols. Cross‐linkers in the sense of this argument are small molecules that have three or more alcohol caps. Their effect is to strengthen the molecule by creating more isocyanate bonds.

They have an important physical effect. Without some amount of cross‐linking (<5%), foaming will not occur. The cross‐linking plays the role of a gelling agent, trapping CO2 (see section on “The Water Reaction”) in the matrix. Without the gelling effect any gases produced would escape leaving a semi‐elastomeric product behind.

The average number of –OH groups can be chosen, and this can lead to a certain controlled amount of cross‐linking. A component can be added to the prepolymer reaction to develop cross‐linking. This has the effect of increasing the number of –OH sites with which the isocyanate can react. This is typically the least expensive way to develop cross‐linking.

The primary method of control, however, is the choice of the degree of functionality of the polyol (number of –OH per molecule) whether this is done with a single polyol or by adding another, typically a low MW polyols. Typical additives to induce cross‐linking are triols like trimethylol propane (TMP), which is considered a hard segment. Very small amounts are needed for soft foam.

An alternative term used for this effect is the functionality. If the functionality is two (a diol), an elastomer results. If, by the addition of a cross‐linker, the functionality is greater than two, foaming occurs (Table 1.1).

Table 1.1 Effect of functionality.

Source: Wood [1]. Reproduced with permission of John Wiley & Sons.

Average functionality

Foam application

2.00

Elastomer

2.07

Carpet‐backing foam

2.12

Soft, integral skin foams

2.21

Automobile cushions

2.49

Semirigid foams

2.70

Rigid foams

3.00

Construction grade rigid foams

The Water Reaction

The last reaction we need to discuss is that of the isocyanates with water. Water reacts with an isocyanate to produce an amine and carbon dioxide gas (Figure 1.6). This is the basis of the PUR foam business. Even with hydrophobics, water is used to create foam, even if much less water is added.

Figure 1.6 The reaction of isocyanates with water.

If one wants an elastomer, one must carefully ensure that there is no water in the polyol. To some degree, the amount of water controls the density of the resultant foam. A typical furniture foam might add from 0.5 to 5% water to the formulation. We will discuss this further when we review the processes. Hydrophilic foam formulations can use more water than the polyols. The reaction with water does not end there. You see from the reaction in the previous figure that there is also an amine coproduct. The amine reacts with an isocyanate to produce a urea linkage (Figure 1.7).

Figure 1.7 The reaction of isocyanates with amines (urea linkage).

It is the water reaction and the amine reaction that results in PUR foam. A foam manufacturer needs to be aware of both reactions. While the production of CO2 is the driving force, unless the amine reaction proceeds, all the CO2 would be lost to the atmosphere. It is the amine reaction coupled with a polyol with a functionality greater than 2 that causes the reacting mass to gel up. In the industry this is called cream time, but for the chemist, the effect is the generation of a three‐dimensional matrix that first traps the CO2. As the mass expands, the internal pressures begin to burst the windows between the cells, thus creating an open‐cell foam.

All this happens under close temperature control. We will cover this further when we turn our attention to the special case of hydrophilic PURs. The two reactions (CO2 and amine) have different activation energies. Higher temperatures favor the CO2 reaction that, if high enough, causes the foam to collapse. The internal pressure is high enough to overcome the strength of the gel and CO2 escapes.

Thus we have described the simultaneous reactions of polymerization and expansion. The juxtaposition of these two reactions is the basis of the PUR foam industry. However, it also has other implications. Consider the commercial of an adhesive brand, an MDI‐based prepolymer with a proprietary polyol. We can guess that it is highly cross‐linked. We can also guess that it uses a hydrophobic polyol. Herein lies a paradox. In advertisements it claims and by our experiments confirms that it is “waterproof” yet it is activated by water. Another property is that it expands to fill, for instance, cracks. A dramatic video in their website shows the bonding of a wood gate to a ceramic post. The animation shows the curing adhesive penetrating both the wood and the ceramic. The question one must ask as a concerned consumer is how all this can be true. The answers are in the discussion of the chemistry given previously.

We know that a prepolymer can be formulated with excess isocyanate and a highly cross‐linked hydrophobic polyol. This is then activated by adding a small amount of water. If not confined in a mold, the activated prepolymer will foam, probably developing closed cells. When the reaction finishes, what remains is a hydrophobic foam. If the activated prepolymer is in a confined space, the expansion penetrates the pores of the two materials. Once fully cured, the two materials are bound together by a strong but brittle elastomer.

This will be discussed further in the process sections but for now it serves as an introduction to process control.

Process

There are two dominant processes by which the chemistries discussed previously are converted into useful products. The first of those combines all the raw materials in the formulation and allows them to react to form the elastomer or foam. In the second process the polyol is capped with the isocyanate and isolated as an isocyanate solution in the polyol. This is the process used for all hydrophilic PURs. We will discuss both processes starting with the more important of the two, the so‐called one‐shot process.

The One‐Shot Process

As chemists we are accustomed to large stirred tanks to which a sequence of chemicals is added and a complex program of heating and cooling. Conventional PUR foam is literally made by slamming together all of the components discussed previously plus some others and then deposited on a conveyor. I use the word slam not without justification. The technical term is impingement, but the effect is the same. In the late 1950s, it was discovered that one could manufacture PUR directly from the component parts using certain surfactants and catalysts. In the one‐shot technique, as it is called, a polyol blend is made containing the surfactant, the catalysts, the blowing agents, and the other components. This blend is then quickly and intimately mixed with an isocyanate phase in what is called an impingement mixer. The fluids are forced together through nozzles, thus creating an emulsion. The emulsion is placed in a mold or other receptacle where the foaming reaction proceeds. Figure 1.8 shows the essential parts of an impingement mixer. As the plunger is withdrawn, the two streams are “slammed” together. Note the several process streams entering the mix head.

Figure 1.8 An impingement mixer.

The following is a typical formulation used in the one‐shot process (Table 1.2):

Table 1.2 Component list for a conventional polyurethane by the one‐shot process.

Source: Adapted from Herrington and Hock [2].

Component

Parts (mass)

Polyol

100

Water

1.5–7.5

Fillers

Variable

Silicone surfactant

0.5–2.5

Amine catalyst

0.1–1.0

Tin catalyst

0.5

Chain extenders

0–10

Cross‐linker

0–5

Isocyanate

25–85

Depending on the amount of water, this formulation list can be used to make elastomers or low‐density foams. In the case of elastomers, the emulsion might be injected into a mold or caste into a sheet. For foams, the emulsion is deposited on a moving conveyor lined with a paper release liner. At this point a time line is set. After a short delay the water reaction begins liberating carbon dioxide and producing the amine coproduct. Shortly thereafter the polyol/isocyanate/amine reaction begins, which increases viscosity first but then begins to develop a gel structure. In the industry this is called cream time; in fact it is a cross‐linked molecular structure capable of trapping the carbon dioxide. The gel matrix continues to increase in strength as more and more carbon dioxide is produced. It is important to note that each of these reactions has different activation energies. Thus temperature affects the reactions at different degrees. In a controlled process, without actually knowing what is going on, the operator is aware of the temperature of the components and the exotherm produced during the reaction. This determines the density and structure of the resultant foam. If properly controlled, as the foam is rising, complex but predictable cell structures separated by windows develop. As the density decreases, those windows become thinner. This happens while the internal pressure created by the carbon dioxide gets high enough to break the windows.

The process is the same whether we are discussing the one‐shot process or the prepolymer process to follow and so it is appropriate to use the following graphic that summarizes the foaming process (Figure 1.9).

Figure 1.9 The foaming process after leaving the mix head.

The result is a stable foam structure. The properties, as we have discussed, depend on the components and temperature of the emulsion. The density of a commercial foam is around 2 lb/ft3. If the thermal conditions are correct, the result is an open‐cell foam, the most common PUR foam.

The Prepolymer Process

The first PURs were made by what has come to be known as the prepolymer process. In the 1950s catalysts and surfactants were developed that made the one‐shot process the preferred technique for foam production.

The prepolymer process involves the manufacture of an “isolated intermediate” that can be stored and sold as a product. Upon exposing the product to a polyol or, in the case of hydrophilic foam, water, the reaction proceeds to make a foam or an elastomeric coating. Prepolymers have experienced a resurgence with the development of PUR paints, coatings, and adhesives. The big advantage of these formulations is they can be produced to have low viscosity and cure in atmospheric moisture. In the case of paints and coating, this technology eliminates the need for volatile organic solvents.

In many prepolymer processes, a small stoichiometric excess of diisocyanate is reacted with the polyol. Again, if the product is to make foam, the polyol has a net functionality greater than two. In the case of hydrophilic PUR, this is accomplished by using polyethylene glycol and a few weight percent trimethylol propane. Water is carefully removed from the reaction mixture, thus ensuring that the reaction occurs between the isocyanate and polyol only. The reaction is conducted between 60 and 120°C. As the isocyanate and polyol react, the viscosity begins to increase. If the prepolymer is to be used for a coating, lower viscosities are desired. For adhesives, a higher viscosity is preferred. For hydrophilic foams, it has become typical that the viscosity of the prepolymer be from 10 000 to 18 000 cps. In any case, at a specified viscosity, the reaction is stopped by cooling. The product is a diisocyanate‐rich solution of a polyol capped with an isocyanate. You will note that the prepolymer is composed of only urethane linkages. When a prepolymer is exposed to water, carbon dioxide is released and amine end groups are formed, restarting the reaction and bringing it to completion. The water can be as little as atmospheric moisture (for an elastomeric coating or adhesive) or in the case of hydrophilic PURs can be as much as one to three times the mass of the prepolymer (Figure 1.10).

Figure 1.10 The prepolymer reaction (the triol is not shown for clarity).

All hydrophilic PURs are made from prepolymers. Several companies sell them and while there is little variability in their specifications, one can choose the level of cross‐linking. There are TDI versions and MDI products. Each has unique characteristics that need to be considered.

As with the one‐shot process, there are specially designed pieces of equipment made for producing foam. In the one‐shot process, the equipment is referred to as “high pressure meter mix” because of the force needed to “impinge” the ingredients. In the prepolymer process to make foam, “low pressure” equipment is used.

Specific to commercial hydrophilic prepolymers, one to three parts of water with a surfactant is mixed in a low pressure mixer and then deposited into a mold or onto a conveyor.

We will explore this to some degree in our research into polyethylene/polypropylene block copolymers. This research was not focused on commercial applications but rather an effort to expand the possibilities. Periodically we will refer to this as a hydrogel. We use an unofficial definition of a hydrogel as a polymer that is capable of absorbing 20+% of its weight in water. Note that this assigns human flesh and all internal organs as being hydrogels or composites thereof.

Regardless of whether one uses the one‐shot process or a prepolymer, if a foam is to be the product, the reaction goes through the stages shown previously, that is, emulsion, gelation, foaming, and curing. The product is typically an open‐cell foam (Figure 1.11).

Figure 1.11 Micrograph of an open‐cell foam.

The degree of openness and whether it is open at all is controlled in the process, but most PUR foams are open to some degree. We will discuss these in the chapter on laboratory practices.

Post Processing