Biological Interactions with Surface Charge in Biomaterials: Volume 21 (Nanoscience & Nanotechnology Series) - Hardcover

Hardcover

ISBN 10: 1849731853 ISBN 13: 9781849731850

Publisher: Royal Society of Chemistry, 2011

Synopsis

This book is the first to comprehensively address the complex phenomenon of biological interactions with the surface charge of biomaterials.

About this title

About the Author

Dr. Syed Tofail, PhD, MSc Eng., BSc Eng., is a Senior Research Fellow with the Materials and Surface Science Institute, University of Limerick, Ireland. He has about 10 years experience in the development and characterisation of nano- and biomaterials. His major research accomplishment is establishing the correct crystal symmetry of hydroxyapatite, a leading synthetic biomaterial. This led him to the discovery of piezoelectricity in synthetic hydroxyapatite. Dr. Tofail is skilled in conducting fundamental research in the field of materials and surface science with the aim of developing medical devices with new functionality. For this, he works closely with relevant industrial players. Dr. Tofail is currently coordinating a European Commission Framework 7 project funded under the Nanotechnology, Materials and Processing (NMP) programme. One of the core objectives of this project is to develop MRSA-resistant medical textiles. In addition, the project will also develop implantable devices for cardiovascular, orthopaedic and urinary applications.

From the Back Cover

When a biomaterial is placed inside the body, a biological response is triggered almost instantaneously. With devices that need to remain in the body for long periods, such interactions can cause encrustation, plaque formation and aseptic loosening on the surface. These problems contribute to the patient's trauma and increase the risk of death. Electrical properties, such as local electrostatic charge distribution, play a significant role in defining biological interactions, although this is often masked by other factors. This book describes the fundamental principles of this phenomenon before providing a more detailed scientific background. It covers the development of the relevant technologies and their applications in therapeutic devices such as MRSA-resistant fabrics, cardiovascular and urological stents, orthopaedic implants, and grafts. Academic and graduate students interested in producing a selective biological response at the surface of a given biomaterial will find the detailed coverage of interactions at the nanometre scale useful. Practitioners will also benefit from guidance on how to pre-screen many inappropriate designs of biomedical devices long before any expensive, animal or potentially risky clinical trials. Enhanced by the use of case studies, the book is divided in to four topical sections. The final section is dedicated to the application of related topics making the book unique in its pragmatic approach to combining high end interdisciplinary scientific knowledge with commercially viable new technologies. Contributing to the newly emerging discipline of 'nanomedicine', the book is written not only by experts from each relevant specialty but also by practitioners such as clinicians and device engineers from industry.

Excerpt. © Reprinted by permission. All rights reserved.

Biological Interactions with Surface Charge in Biomaterials

By Syed A.M. Tofail

The Royal Society of Chemistry

Copyright © 2012 Royal Society of Chemistry
All rights reserved.

ISBN: 978-1-84973-185-0

Contents

Part I Electrostatic Charge on Biomaterials' Surfaces, 
Chapter 1 Electrical Modifications of Biomaterials' Surfaces: Beyond Hydrophobicity and Hydrophilicity S. A. M. Tofail and A. A. Gandhi, 3, 
Chapter 2 Photocatalytic Effects in Doped and Undoped Titania M. Kopaczynska, M. Vargová, K. Wysocka-Król, G. Plesch and H. Podbielska, 15, 
Chapter 3 Surface Charge Measurements on Biomaterials in Dry and Wet Conditions M. Gregor, T. Plecenik, A. Plecenik, C. Wolf-Brandstetter D. Scharnweber and S. A. M. Tofail, 26, 
Chapter 4 Non-linear Characterizations of Surface Charge and Interfacial Morphology S. B. Lang, G. A. Stanciu and S. G. Stanciu, 45, 
Part II Protein Interactions at the Surface, 
Chapter 5 Immobilization of Enzymes on Porous Surfaces P. Periyat and E. Magner, 65, 
Chapter 6 Fibrous Proteins Interactions with Modified Surfaces of Biomaterials C. Wolf-Brandstetter and D. Scharnweber, 75, 
Chapter 7 Antibody Immobilization on Solid Surfaces: Methods and Applications X. Hua, I. B. O'Connor and J. G. Wall, 90, 
Part III Cellular Interactions with Abiotic Surfaces, 
Chapter 8 Interactions of Bone-forming Cells with Electrostatic Charge at Biomaterials' Surfaces U. Hempel, C. Wolf-Brandstetter and D. Scharnweber, 107, 
Chapter 9 Interactions of Biofilm-forming Bacteria with Abiotic Surfaces S. Robin, T. Soulimane and S. Lavelle, 122, 
Chapter 10 Endothelial Cells and Smooth Muscle Cells: Interactions at Biomaterials' Surfaces M. Wawrzynska, B. Sobieszczanska, D. Biazy and J. Arkowski, 136, 
Chapter 11 Interactions of Bacteria and Fungi at the Surface E. Dworniczek, R. Franiczek, U. Nawrot and G. Gosciniak, 148, 
Chapter 12 Immunological Response of Electrostatic Charge at the Surface of Biomaterials B. Sobieszczanska, M. Wawrzynska and D. Biazy, 161, 
Part IV Applications, 
Chapter 13 Community-and Hospital-acquired Staphylococcal Infections R. Thornton and J. Cooney, 175, 
Chapter 14 MRSA-resistant Textiles J. Bauer, K. Kowal, S. A. M. Tofail and H. Podbielska, 193, 
Chapter 15 Inhibition of Encrustationin Urological Devices S. Robin, T. Soulimane and S. Lavelle, 208, 
Chapter 16 The Reduction of Restenosis in Cardiovascular Stents J. Arkowski, M. Wawrzynska, D. Biazy, B. Sobieszczanska and W. Mazurek, 222, 
Chapter 17 Manipulation of Interfaces on Vector Materials N. Horiuchi, M. Nakamura, A. Nagai and K. Yamashita, 230, 
Subject Index, 249, 

CHAPTER 1

Electrical Modifications of Biomaterials' Surfaces: Beyond Hydrophobicity and Hydrophilicity

S. A. M. TOFAIL AND A. A. GANDHI

1.1 Introduction

When a biomaterial is placed inside the body, a biological response is triggered almost instantaneously at the top few nanometres of the biomaterial. It is commonly understood that electrical properties such as local electrostatic charge distribution at biomaterials' surfaces play an important role in defining biological interactions e.g. protein adsorption and cell adhesion. Protein adsorption is the initial event that takes place within the first few milliseconds at the biomaterial surface. The adsorbed proteins interact with selected cell membrane protein receptors. The accessibility of cell adhesive domains (such as various specific amino acids of adsorbed vitronectin, fibronectin and laminin) may either enhance or inhibit subsequent cell attachments and proliferation.

Biological membranes such as those found in cell membranes are subjected to an electrical field gradient in excess of 10 mV m-1. In other words, a cell with a thickness of few nanometres is subjected to an electromotive force of few millivolts. In a physiological environment, this substantial electric potential will essentially polarize its surrounding body fluid to form an electrical double layer. Similar double layers are formed around proteins and other biomolecules and biomedical device surfaces in vivo. Interactions of biomolecules with biomedical device surfaces thus can be seen as interactions between these double layers, which are further influenced by ionic interactions, chemotaxis and biochemical factors. The thickness of these double layers is dependent on the magnitude of the surface charge and usually lies in the nanometer range.

The adsorption of biological species is promoted primarily by two types of physical forces, electrostatic attractions and hydrophobic interactions. Most inorganic surfaces are negatively charged at normal pH, but usually they also contain hydrophobic domains. There can also be spatial variations of polarity of surface charge (Figure 1.1). A protein usually has positive, negative and hydrophobic patches thus enabling a protein to be attracted to most surfaces, on the one hand, by electrostatic attractions between positive patches and negatively charged groups on the surface, and, on the other hand, by hydrophobic interactions between hydrophobic domains of the protein and the surface.

For control and utilization of the adhesion and growth of biological species, e.g. proteins and cells, adhesion mechanisms on biomaterials used in implantable devices need to be properly understood. Biomaterials that are currently used in such devices, e.g. in cardiovascular and urinary stents and coatings in hip prosthesis, do not specifically address this interfacial phenomenon in device designs. For devices that remain in the body for medium to long term, biological interactions can cause encrustation, plaque formation and aseptic loosening in these device surfaces. These problems contribute to a patient's trauma and even increase the risk of death. A detailed knowledge of such interactions will not only help to produce a desired biological response but also pre-screen many inappropriate designs of biomedical devices long before any expensive animal or potentially risky clinical trials. Electrical modification of biomaterials can thus serve dual purposes: it can help in the understanding of biological interactions and, in turn, provide knowledge to engineer surface charge in biomaterials for improved medical devices.

1.2 Characteristics of Biomaterials' Surfaces and their Modifications

Relevant surface characteristics of biomaterials can be listed as follows:

• Contact angle (hydrophobicity/hydrophilicity)

• Electrical Charge

• Topography and roughness

• Porosity (pore diameter, interconnectedness, open and closed pores, pore orientation) and surface area

• Mechanical compliance/stiffness/hardness

• Water content (dry/wet)

• Chemistry (elements present, contamination overlayer, the presence of polar/non-polar group, dangling bonds, acid–base characteristics)

• Crystallinity, surface relaxation and reconstruction.

These characteristics are greatly affected and often unintentionally modified by: packaging and exposure to environment (e.g. hydrocarbon contaminants), handling (e.g. contamination, alteration of topography), storage (e.g. residual stresses can result in dimensional changes) and sterilization process (temperature, water absorption, duration of heating, the use of ionizing radiation, the use of oxidizing gases and duration of degassing).

At present, biomedical devices are designed primarily for functional uses while maintaining the inertness of the device so that, when used, they do not create any adverse effect in the biological system. Biomaterials' surfaces form an interface between two entirely different systems: biological and nonbiological. The surface properties of the biomedical device play a critical role in defining the bio- logical response. Present day surface engineering of biomedical devices is focused on modifying the topography, surface chemistry, wettability, water stability and water-binding properties of the biomaterial surface.

In order to develop the next generation of biomaterials, emphasis must be placed on bioactivity rather than the material's bio-inertness. To achieve this end, there has been an increased interest in the modification of the surfaces chemically [e.g. by using plasma, surfactants or functional groups, or drugs), mechanically (e.g. by roughening the surface) and biologically (e.g. by modifying surface with ribonucleic acid (RNA)]. While a plethora of information is now available that describes the effects of such modifications on biological interactions, the interdependent nature of such modifications poses a problem in determining the exact role of different processes in a biological environment.

Protein interactions with polymers and other biomaterials used in medical devices, particularly cardiovascular and blood-contacting surfaces, have been studied for a long time. Table 1.1 provides a list of variables critical in designing biomaterials' surfaces for a specific application and their corresponding protein properties. The importance of electrical properties of biomaterials' surfaces to trigger a specific protein response can be readily seen in Table 1.1. What is absent from current day biomedical device design is an adequate consideration of the surface charge, its distribution and the electrical double layer potentials, which are interrelated and critical in defining biological interactions (Table 1.1).

Surface engineering of biomaterials to produce a desired topography, morphology, chemistry or hydrophilicity/hydrophobicity can have important implications for surface charge to the extent that the beneficial effects of the engineering can be compromised. This, in turn, results in unreliable performance of biomedical devices in vivo. Another important issue is the effect of sterilization on surface charge and the performance of implantable devices. As it will be discussed in the following sections, the sterilization method can itself create surface charge in devices. Unfortunately, there are inadequate investigations and data available on the effect of sterilization. The current limitations of medical device design can be summarized as below:

• A focus on biofunctionality and bio-inertness

• Bio/non-bio interactions at the surface are largely ignored

• Surface charge at the device surface is not a design criterion

• Hydrophobic, hydrophilic and neutral patches on the same surface make control of biological response extremely difficult

• Quantitative insight to biological reactions at the surface is absent

• Performance of bio-inert surfaces is unreliable and contributes to patients' trauma and risk of death

• the effect of sterilization on device performance is not adequately known.

1.3 Electrical Modifications of Biomaterials' Surfaces

Electrical modifications of Biomaterials' surfaces depend on the ability of certain biomaterials to possess, store or generate surface charge under suitable conditions. Metallic biomaterials are good conductors of electricity and do not store charge. Thin metal oxide layers grown naturally or artificially on these metals usually possess semiconducting properties. These layers, if grown sufficiently thick, can work as an insulator, which can be polarized electrically. Examples will be anodically grown oxides of Ti or Ta on Ti or Ta metals or alloys. Alternatively, a sufficiently thick layer of the metal oxide deposited by chemical or physical means can also be polarized. Common polymeric and ceramic biomaterials are insulators and can be used as coatings or devices and can be electrically modified by electrical polarization.

When insulators are polarized, and if they can store this polarization, they are called 'electrets': a material that has a permanent macroscopic electric field at its surface. In reality, the term 'permanent' in the definition may be misleading as electret polarization is subject to decay due to thermal, internal and environmental reasons but this decay time can be sufficiently long. This has made possible wide applications of electrets in electronics and xerography. 'Dipolar electrets' are overall electrically neutral but possess a macroscopic electrical dipole moment, which gives rise to the 'vectorial' effect (discussed in Chapter 17). Slow cooling of an insulator from a high temperature in the presence of a high electric field produces a dipolar electret due to the dipoles being 'frozen' with a net orientation along the direction of the applied field. This is normally referred to as the 'contact poling' process. This gives rise to the dipolar charge originating from the alignment of dipoles in dipolar materials containing dipolar molecules, and in ferroelectric materials. 'Space charge electrets', on the other hand, possess a net macroscopic electrostatic charge that results from the addition of charge to the surface and bulk of a material by bombarding it with an electron beam, ion beam or corona, contacting directly with a charged electrode, or transferring ions to or from the material being 'poled'.

Electrical charges can be created and stored in an electret in the form of dipolar or real charges. Real charges, when they occur at the surface, are called 'surface charge'. When they occur in the bulk, they are called 'space charge'. Most insulating materials, especially organic materials, are space charge electrets. Even in a dipolar electret, space charges can form during the 'poling' process due to trapped charges in defects or grain boundaries from the surface to deep inside the bulk of the insulator. This is why the term 'surface charge' can often be ambiguous, as the method of creating such surface charge may also induce dipolar charges and, more occasionally, space charges.

It is also imperative to discuss the polarity of the surface after electrical modification. Surface charges or space charges with polarity similar to the adjacent forming electrodes are called 'homocharges' and those with opposite polarity are called 'heterocharges'. Homocharges may occur as a result of charge carrier injections from an electrode or charge source (electron beam, ion beam or corona), followed by the capture of injected carriers in traps near the place of charge injections. While this sounds simple, the spatial distribution of such homocharges can be quite complex and, in the case of poling with the help of electron beam, can also give rise to significant amount of 'heterocharges' due to the dynamic balance between primary electron, secondary emission electrons and the positive holes created at the surface region due to electron emission. Electret domains created by electron beam can show both positive and negative charges at the surface and sub-surface zone.

A simple way of modifying surfaces electrically is to apply a coating which is known to be highly electropositive or electronegative. In the cases where a minimum chemical change at the surface is desired, artificial polarization is employed to produce an ordering of molecular dipoles or an uncompensated surface charge. The generation of surface charge will ideally involve very little or no change in the chemistry, topography or morphology of the surface, as such a modification of the surface, in turn, can alter the surface charge characteristics. Various methods can be employed in this pursuit, such as:

(i) Thermoelectrical poling with solid contact

(ii) Liquid-contact poling

(iii) Corona discharge poling

(iv) The electron beam method

(v) Electromagnetic radiation poling.

Conventional thermoelectrical poling requires metallic coating on the two opposite surfaces of an insulator and may not be suitable for poling biomaterials. Yamashita et al. has eliminated this problem by simply sandwiching a hydroxyapatite ceramic pellet between two platinum electrodes, which were removed after poling was complete. The nature of the contact between the electrode and the insulator can have important implications for the polarity of the charge, as a small air gap can give rise to surface monocharges in addition to the dipolar charges. After the removal of the applied field, the total polarization gradually decreases to a quasi-steady level, which is mainly the remaining 'frozen' dipolar polarization associated with the difference in relative permittivity between the ambient and the poling temperature.

To our knowledge, liquid-contact poling has not been reported for poling biomaterials. In this method one of the electrodes is a conductive liquid such as ethanol or water. Similar poling can be achieved by using a solid material that is liquid and conductive at the poling temperature. In this method the control of charge density is easier and the lateral charge distribution is uniform. Corona discharge poling is described in Chapter 4 and will not be described here. Electron beam poling is usually used to produce real charges stored in the bulk of the material. A 20 keV field has been used in a traditional scanning electron microscope to polarize local micron-scale areas of hydroxyapatite thin films. Hydroxyapatite ceramic pellets have also been poled with lower energy electron beams (<1 keV). In a thermal equilibrium state a very stable distribution of negative charges can form. The electron beam poling method has the advantages of an easily controllable density, location and lateral distribution of the injected negative charge. Ion beam implantation or ion beam poling, while similar in principle, has the disadvantages of damaging the material due to the larger size of the ions.

Electromagnetic radiations such as Gamma ray, X-ray, ultraviolet (UV) or visible light can also produce electrets under an external electric field, which is usually applied through transparent conductive electrodes. Under an electric field, photogenerated carriers will be separated and will move to the electrodes of opposite polarities. These carriers may be trapped near the electrodes to create a space charge polarization. After removal of the radiation and the electric field, the charge distribution enters into a quasi-equilibrium state and decays. These electrets are less stable than the ones described earlier. The radiation method has rarely been used for polarizing biomaterials.

Similar to nanomagnets, 'nanoelectrets' can also be produced by exploiting the methods described above. Discrete nanodomains can be created at the surface of such electrets to obtain a surface charge at the nanoscale level and can offer the advantage of studying biological interactions with electrostatic charge at high lateral resolutions. The principles of electrical modification to obtain discrete electrostatic domains with high lateral resolution in the nano, submicron and micron scale can be listed as follows:

• direct manipulation of the surface by applying a dc electric field through a conductive tip (Figure 1.2) in a scanning probe microscope (SPM). This can be accomplished within the settings of an electrostatic force, a piezoresponse force or a Kelvin force microscopy. The nanoresolutions of SPM in lateral dimensions facilitate the achievement of discrete domains of preferentially charged electrostatic domains.

(Continues...)

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Edition details

• Publisher: Royal Society of Chemistry
• Publication date: 2011
• ISBN 10: 1849731853
• ISBN 13: 9781849731850
• Binding: Hardcover
• Language: English
• Number of pages: 276
• Editor: Syed Tofail