Contents

Cover

Title page

Copyright page

Preface

Part 1: General Topics

Chapter 1: Theories and Mechanisms of Adhesion in the Pharmaceutical, Biomedical and Dental Fields
1. 1.1 Introduction
2. 1.2 Mechanisms of Adhesion
3. 1.3 Summary
4. References
Chapter 2: Wettability of Powders
1. 2.1 Introduction
2. 2.2 Different Forms of Wetting
3. 2.3 Hydrophilic and Hydrophobic Surfaces
4. 2.4 Contact Angle Measurement in Wettability Studies of Powdered Materials
5. 2.5 Contact Angle and Surface Free Energy
6. 2.6 Surface Free Energy Determination of Powdered Solids by Thin Layer Wicking Method
7. 2.7 Surface Free Energy Determination of Powdered Solids by Imbibition Drainage Method
8. 2.8 Summary
9. Acknowledgement
10. References

Part 2: Adhesion in the Pharmaceutical Field

Chapter 3: Tablet Tensile Strength: Role of Surface Free Energy
1. 3.1 Introduction
2. 3.2 Applicability of the Proposed Model to Pharmaceutical Materials
3. 3.3 Discussion
4. 3.4 Summary
5. 3.5 Acknowledgements
6. References
Chapter 4: Role of Surface Free Energy in Powder Behavior and Tablet Strength
1. 4.1 Introduction
2. 4.2 Surface Free Energy
3. 4.3 Role of Surface Free Energy in Solid Wetting
4. 4.4 Role of Surface Free Energy in Powder Flow
5. 4.5 Role of Surface Free Energy in Powder Tableting
6. 4.6 Concluding Remarks
7. References
Chapter 5: Mucoadhesive Polymers for Drug Delivery Systems
1. 5.1 Introduction
2. 5.2 Mucoadhesive Drug Delivery Systems
3. 5.3 Mucoadhesive Polymers
4. 5.4 Summary
5. References
Chapter 6: Transdermal Patches: An Overview
1. 6.1 Introduction
2. 6.2 Factors Affecting Skin Absorption
3. 6.3 Passive Transdermal Drug Delivery Systems
4. 6.4 Types, Structural Components and Materials Used to Design Passive TDDS
5. 6.5 Active Transdermal Drug Delivery Systems
6. 6.6 Production of Transdermal Patches
7. 6.7 Biopharmaceutical Concerns
8. 6.8 Pharmacokinetics of Transdermal Absorption
9. 6.9 Manufacture, Design and Quality Control
10. 6.10 Commercialized Patches
11. 6.11 Regulatory Aspects
12. 6.12 Summary and Future Prospects
13. Acknowledgement
14. References
Chapter 7: Film-Forming Technology and Skin Adhesion in Long-Wear Cosmetics
1. 7.1 Introduction
2. 7.2 Long-Wear Foundation: An overview
3. 7.3 Effect of Skin Substrate on Adhesion
4. 7.4 Long-Wear Technologies in Cosmetic Applications
5. 7.5 Summary and Prospects
6. Acknowledgements
7. References

Part 3: Adhesion in the Biomedical Field

Chapter 8: Factors Affecting Microbial Adhesion
1. 8.1 Introduction
2. 8.2 Surface Characterization
3. 8.3 Bacterial Adhesion to Material Surfaces
4. 8.4 Summary
5. Acknowledgments
6. References
Chapter 9: Factors Influencing Biofouling and Use of Polymeric Materials to Mitigate It
1. 9.1 Introduction
2. 9.2 Origin of Biofouling
3. 9.3 Prevention of Micro-Organisms Adhesion
4. 9.4 Influence of Mechanical Properties
5. 9.5 Influence of Surface Topography
6. 9.6 Concluding Remarks
7. References
Chapter 10: Coatings on Surgical Tools and How to Promote Adhesion of Bio-Friendly Coatings on Their Surfaces
1. 10.1 Introduction
2. 10.2 Coatings on Various Surgical Tools and Implants in Different Fields of Operative Care to Patients
3. 10.3 Promotion of Adhesion of Bio-Friendly Coatings on Surfaces of Tools and Implants
4. 10.4 Summary
5. References
Chapter 11: Techniques for Deposition of Coatings with Enhanced Adhesion to Bio-Implants
1. 11.1 Bio-Implants: An Introduction
2. 11.2 Deposition Methods for Enhanced Adhesion of Coatings on Implants
3. 11.3 Summary
4. References
Chapter 12: Relevance of Adhesion in Fabrication of Microarrays in Clinical Diagnostics
1. 12.1 Introduction
2. 12.2 Protein Microarrays
3. 12.3 DNA Microarrays
4. 12.4 Antibody Microarrays
5. 12.5 Summary
6. References

Part 4: Adhesion in the Dental Field

Chapter 13: Antibacterial Polymers for Dental Adhesives and Composites
1. 13.1 Introduction
2. 13.2 Major Damage from Oral Biofilm Formed: The Acid Production
3. 13.3 The Chemistry of Current Dental Adhesives and Composites
4. 13.4 The Need for Treatments Targeting Oral Cariogenic Biofilms
5. 13.5 Classification of Antibacterial Polymers for Dental Materials
6. 13.6 Mechanisms of Action of Antibacterial Monomers
7. 13.7 Antibacterial Properties of Dental Adhesives and Composites Containing Antibacterial Monomers
8. 13.8 Considerations of Mechanical Properties
9. 13.9 Summary and Prospects
10. Acknowledgments
11. Summary
Chapter 14: Dental Adhesives: From Earlier Products to Bioactive and Smart Materials
1. 14.1 Introduction
2. 14.2 Adhesion to Dental Substrates
3. 14.3 Adhesive Strategies
4. 14.4 Limitations in Bonding to Dental Substrates
5. 14.5 Strategies to Reduce Bond Strength Degradation – Current Advances
6. 14.6 Summary and Prospects
7. Acknowledgement
8. References
Chapter 15: Testing of Dental Adhesive Joints
1. 15.1 Introduction
2. 15.2 Various Bond Strength Tests
3. 15.3 Summary
4. References

Index

End User License Agreement

List of Tables

Chapter 1

Table 1.1: Examples of adherend and adhesive types in the human body.
Table 1.2: General materials related to adhesion and their assessment methods.
Table 1.3: Comparison of adhesion interactions relative to length scale.
Table 1.4: Orders of scale for adherend-adhesive interactions in the pharmaceutical, biomedical and dental fields.
Table 1.5: Concepts and quantities important in electrostatic adhesion.
Table 1.6: Bond strengths of various types of chemical bonds and intermolecular forces.

Chapter 2

Table 2.1: Parameters for hydrophilicity/hydrophobicity measure of solid surfaces [11].

Chapter 5

Table 5.1: Summary of various techniques used for the assessment of mucoadhesive interactions at the macroscopic level.
Table 5.2: Summary of various techniques for the assessment of mucoadhesive interactions at the molecular level.
Table 5.3: Mucoadhesive dosage forms and polymers used in the formulation [10].
Table 5.4: Classification, categories and examples of different mucoadhesive polymers.
Table 5.5: Lectin modified polymers for the development of mucoadhesive drug delivery systems.
Table 5.6: Thiolated polymers investigated for developing mucoadhesive drug delivery systems.

Chapter 6

Table 6.1: Materials commonly used for the design of transdermal patches.
Table 6.2: Selected marketed transdermal patches along with their therapeutic applications.
Table 6.3: Regulatory aspects for approval of transdermal drug products.

Chapter 7

Table 7.1: Summary of skin surface free energy before and after degreasing on volar forearm and forehead.
Table 7.2: Young’s modulus determined in vivo using various methods for different skin regions and ages.

Chapter 8

Table 8.1: Roughness (R_q) and water contact angles on five different glass surfaces, five different stainless steel surfaces (AISI 304) and polystyrene surface. N means untreated glass surface. 3C is the untreated stainless steel surface.

Chapter 11

Table 11.1: Comparison between different methods used for coating of implants.
Table 11.2: Adhesion strengths (in MPa) of different coatings to Ti and CoCrMo substrates [57].

Chapter 12

Table 12.1: Fabrication parameters with respect to the different fabrication techniques. (adapted from Schena, 2002 [5])
Table 12.2: Fabrication techniques for protein and DNA microarrays. (Reprinted from [4] with kind permission from Royal Society of Chemistry)
Table 12.3: Various methods for coupling proteins on a microarray platform. (adapted from Kambhampati, 2006 [36])
Table 12.4: Examples of commonly available glass-based microarray platforms. (adapted from Kambhampati, 2006 [36])
Table 12.5: Examples of common polymer and hydrogel substrates.
Table 12.6: Examples of substrate modifications with modified chemical groups
Table 12.7: Light induced attachment of ligands
Table 12.8: Tagged proteins and their corresponding immobilization systems which are commercially available
Table 12.9: Various immobilization methods for DNA probes.
Table 12.10: The favorable and non-favorable aspects of functionalized DNA chip surfaces [88].
Table 12.11: Solid phase support materials for coupling of biochemical species [101].

Chapter 15

Table 15.1: Mean bond strength values for ten different dentin adhesives used by private practitioners participating in continuous educational courses.

List of Illustrations

Chapter 1

Figure 1.1: Micrograph of the porous structure of bone (Courtesy of Michael Mason, University of Maine).
Figure 1.2: Schematic of the formation of an adhesion bond attributed to transfer of charge from an electropositive material to an electronegative material.
Figure 1.3: Interaction between electrically charged particles. F1 and F2 are the forces of interaction between two point charges (q₁ and q₂) and the distance (r) between them.
Figure 1.4: Schematic of diffusion mechanism of adhesion: (a) two compatible materials are brought into close contact (b) and an interphase (c) is formed where both materials mix and/or entangle with one another.
Figure 1.5: Hydrolysis of an organofunctional silane and reaction of a hydrolyzed organosilane with a hydroxyl functional substrate (Adapted from [4]).
Figure 1.6: Characteristics of mechanical and chemical weak boundary layers.
Figure 1.7: Behavior of a tacky (sticky) elastomeric adhesive used in bonding wood.

Chapter 2

Figure 2.1: 2D illustration of contact angle formed by a liquid drop in equilibrium with its vapor, where: γ_SV is the solid surface free energy, γ_LV is the liquid surface free energy (surface tension), γ_SL is the solid/liquid interfacial free energy, and θ is the equilibrium (Young) contact angle.
Figure 2.2: Illustration of wetting process versus the contact angle and work of spreading.

Chapter 3

Figure 3.1: Ryshkewitch-Duckworth plots for dicalcium phosphate, lactose and sodium dodecyl sulfate (SDS) at several dwell times. As suggested in an earlier publication [23] no dwell time dependence is noted. If data are missing for a given dwell time then tablets were not formed at this dwell time. Points represent data for individual tablets.
Figure 3.2: Ryshkewitch-Duckworth plots for dicalcium phosphate and sodium dodecyl sulfate (SDS) mixtures at several dwell times. As suggested in an earlier publication [23] no dwell time dependence is noted. If data are missing for a given dwell time then tablets were not formed at this dwell time. Points represent data for individual tablets.
Figure 3.3: Ryshkewitch-Duckworth plots for lactose and sodium dodecyl sulfate(SDS) mixtures at several dwell times. As suggested in an earlier publication [23] no dwell time dependence is noted. If data are missing for a given dwell time then tablets were not formed at this dwell time. Points represent data for individual tablets.
Figure 3.4: Ryshkewitch-Duckworth parameters for lactose and sodium dodecyl sulfate (SDS) mixtures. Results conform to the proposed model and Eqns. (3.19) and (3.20). The 90% confidence interval of the least squares fit is indicated by the dashed lines. The solid line is the least squares fit to the data points.
Figure 3.5: Ryshkewitch-Duckworth parameters for dicalcium phosphate and sodium dodecyl sulfate (SDS) mixtures. Results conform to the proposed model and Eqns. (3.19) and (3.20) The 90% confidence interval of the least squares fit is indicated by the dashed lines. The solid line is a least squares fit to the data points.
Figure 3.6: Ryshkewitch-Duckworth plots for starch and mannitol mixtures with sodium dodecyl sulfate (SDS).
Figure 3.7: Ryshkewitch-Duckworth parameters for starch and sodium dodecyl sulfate (SDS) mixtures. Results conform to the proposed model and Eqns. (3.19) and (3.20). The 90% confidence interval of the least squares fit is indicated by the dashed lines. The solid line is a least squares fit to the data points.
Figure 3.8: Ryshkewitch-Duckworth parameters for mannitol and sodium dodecyl sulfate (SDS) mixtures. Results conform to the proposed model and Eqns. (3.19) and (3.20). The 90% confidence interval of the least squares fit is indicated by the dashed lines. The solid line is a least squares fit to the data points.
Figure 3.9: Tensile strength versus porosity for a drug formulation containing a drug compound (A), l-arginine, poly(ethylene glycol) 8000, SDS and mannitol [24]. Circles – tablets prepared using direct compression of the physical mixture. Squares - tablets prepared using wet granulation. Wet granulation reduces tensile strength. Dashed line – Prediction using Ryshkewitch-Duckworth (R-D) parameters for individual components.
Figure 3.10: Tablet tensile strength versus porosity for two individual components (drug compound A and PEG 8000) of the formulation discussed in Figure 3.9 [24]. Circles - neat compound. Squares - wet granulation. Dashed line – prediction using Ryshkewitch-Duckworth parameters for neat compound.
Figure 3.11: Left- tensile strength vs. porosity for microcrystalline cellulose at different water activities (%RH). Right – tensile strength versus water content for microcrystalline cellulose at different porosities. Water content is determined by water activity. Vertical dashed line represents monolayer coverage by water. Plots redrawn from data by Sun [25]. Data suggest that adsorbed water reduces adhesion between power particles.
Figure 3.12: Tablet tensile strength versus surface free energy, γ, for several materials. Figure drawn from data by El Gindy and Samara [28].
Figure 3.13: Tablet tensile strength versus γ^LW for several materials. PVC - poly (vinyl chloride). Emcompress - calcium hydrogen phosphate dihydrate. PTFE - poly(tetrafluoroethylene). Corvic - vinyl chloride -vinyl acetate copolymer. Figure is drawn from data by Luangtana-Anan and Fell [29].
Figure 3.14: Total contact area between particles vs tablet porosity during compression and decompression. Contact area has been normalized with respect to the projected area of the smallest particle, (πr²). A linear relation between tablet porosity and contact area exists for porosities below approximately 40. MCC - microcrystalline cellulose. Figure redrawn from data by Yohannes et al. [30].

Chapter 4

Figure 4.1: Dependence of potential energy, U(r), and inter-molecular force, F(r), on intermolecular separation, r. At the separation distance r₀, the intermolecular force is zero. At the separation distance of r₀ + r_t, the intermolecular attractive force is the maximum.
Figure 4.2: An illustration of contact angle between a liquid drop and a solid surface.
Figure 4.3: A 2D hypothetical crystal structure under tensile stress. At the maximum tensile strength, σ_max, the intermolecular separation distance, d, is equal to F(r₀ + r_t) (see Figure 4.1).

Chapter 5

Figure 5.1: Schematic representation of interaction of thiolated polymer (thiomer) with the mucin leading to strong mucoadhesive bond between the polymer and mucin.

Chapter 6

Figure 6.1: Cross-sectional diagram of the major skin layers, namely stratum corneum and viable epidermis.
Figure 6.2: Three basic common designs to fabricate a passive transdermal skin-patch include, (1) a three-layer skin-patch system consisting of backing layer, drug & skin contact adhesive layer, and temporary release liner to peel off; (2) a five-layer skin-patch system comprising of backing layer, drug reservoir/adhesive layer, rate-controlling membrane as a laminate structure, drug & skin contact adhesive layer, and temporary release liner; (3) a five-layer skin-patch system: backing layer, sealed liquid drug reservoir layer, a rate-controlling membrane as a laminate structure, drug & skin contact adhesive layer, and temporary release liner.
Figure 6.3: Linear kinetic model for percutaneous dermal absorption. Where, K(in): Rate of drug input/release to stratum corneum from the patch; K(r) Rate of reverse drug diffusion from the stratum corneum; K(1) Rate of drug diffusion across stratum corneum; K(2) Rate of drug diffusion across viable epidermis; K(3) Reverse drug diffusion rate constant; and K(4) Rate of drug diffusion across systemic circulation.
Figure 6.4: Design of diffusion-cell apparatus for the investigation of in vitro skin permeation studies of transdermal patches.
Figure 6.5: Schematic diagram for the production of transdermal patches.

Chapter 7

Figure 7.1: Structure of human skin.
Figure 7.2: “T- zone” area comprising the forehead, nose and chin.
Figure 7.3: Morphological alteration of PDMS from low viscous fluid to highly cross-linked resin (adapted from reference [51]).
Figure 7.4: The trend in foundations using silicone fluid, silicone gum, silicone resin and film-former for comfort or long- lasting wear.
Figure 7.5: The structure of an MQ resin.
Figure 7.6: Linear PDMS cross-linked with a silicone resin MQ.
Figure 7.7: MQ resin dispersed in the thermoplastic nylon-611/dimethicone polymer.
Figure 7.8: T- propyl silsesquioxane resin with a ladder-like structure (a) or loose cage structures such as in (b) or (c).
Figure 7.9: Structure of acrylate polytrimethylsiloxymethacrylate copolymer.

Chapter 8

Figure 8.1: Optical density at 620 nm (OD₆₂₀) of different glass surfaces. The adhered cells of E. coli ATCC35218 were stained with crystal violet and examined after 18 h [57].
Figure 8.2: Optical density at 620 nm (OD₆₂₀) of different metal surfaces. E. coli ATCC 35218 was used [58].
Figure 8.3: SEM micrographs of the surface with adhered bacteria, a – electropolished surface, b – brushed surface. Both micrographs were taken after 24 h.
Figure 8.4: SEM image of polystyrene surface covered with microorganisms (P aeruginosa) after 24 h.

Chapter 9

Figure 9.1: Steps and timescale of biofilm formation: I) a conditioning film containing proteins is formed on the surface; II) microorganisms settle on the conditioning film; III) microorganisms adhere and produce Extracellular Polymeric Substance (EPS).
Figure 9.2: Balance among the surface and interfacial tensions of a liquid drop onto a solid at the thermodynamic equilibrium (Young’s equation).
Figure 9.3: Liquid droplet resting on air pockets (fakir droplet).
Figure 9.4: Illustration of chain hydration of (left) hydrophilic polymers (e.g. PEG), and (right) zwitterionic polymers.
Figure 9.5: Structure of a polyampholite.
Figure 9.6: Baier curve: degree of biological fouling vs critical surface tension of polymeric substrates (redrawn from data in [37]).
Figure 9.7: Relative adhesion as a function of the square root of the product of critical surface tension and elastic modulus: dots are experimental data for a series of common polymers (redrawn from data in [47]).

Chapter 10

Figure 10.1: Schematic diagram of the bipolar tips coated with Teflon in a stripped manner.
Figure 10.2: AFM images of multilayers of TiO₂-chitosan/heparin: (a) one bilayer (b) two bilayers (c) three bilayers. Reprinted from [39] with permission from John Wiley & Sons, Inc.
Figure 10.3: Evidence of bactericidal efficacy of antibiotics after their release from coating at a concentration of 10³ CFU. Groups I and II show agar plates (no coating) carpetted with bacteria. Groups III and IV show agar plates (with coating) with less number of bacteria. Reprinted from [49] with permission from John Wiley & Sons, Inc.
Figure 10.4: (a) An overview of YSZ-CP coated dental screw (b) SEM image of coated screw. Reprinted from [54] with permission from John Wiley & Sons, Inc.
Figure 10.5: Schematic of the implanted pressure sensor on the iris showing high sensitivity pressure response.
Figure 10.6: Schematic showing a comparison of typical flat implants with different coatings 6 weeks post-op. (a) SiO₂ coating appears to induce significant fibrosis over the implant, (b) IrOx causes a mild gliosis above the implant, pointed by an arrow, (c) Parylene-C coating allows the deposition of the INL in close proximity to the implant.
Figure 10.7: Schematic illustrating entrapped contaminants: (a) between the coating and the substrate layer (b) within the coating layer and the substrate.

Chapter 11

Figure 11.1: Schematic diagram of a typical RF magnetron sputtering facility [15].
Figure 11.2: AFM images of surfaces of ITO films (a) deposited without intentional heating and (b) deposited at 70 °C[74].
Figure 11.3: Plasma spraying equipment.
Figure 11.4: Schematic diagram of a typical plasma spraying process.
Figure 11.5: Single-edge notch-bending specimen (also called three-point bending specimen) for fracture toughness testing, where P is the applied load, B is the thickness of the specimen, a is the crack length, and W is the width of the specimen.
Figure 11.6: Schematic diagram of PLD system [63].
Figure 11.7: Comparison of adhesion strengthof HA coatings on substrates with different pre-treatments: Specimen 1 (mirror finish), specimen 2 (60 grit grinding), specimen 3 (320 grit grinding), specimen 4 (etched with Knoll solution (10% HF + 40% HNO₃ + 50% H₂O)), and specimen 5 (nitriding + etching). The surface roughness is also indicated in parentheses in each specimen [71].

Chapter 12

Figure 12.1: Overview of microarray applications in pathogen detection (Reprinted from [3] with kind permission from Elsevier)
Figure 12.2: Schematic of PISA technique (Reprinted from [4] with kind permission from Royal Society of Chemistry).
Figure 12.3: Representation of gold surface with long chain alkanethiol layer (monolayer) like 16 mercaptohexadecanoic acid having various functional groups at the terminals such as 1. Biotin, 2. NHS N-hydroxysuccinimide, 3. Epoxy ethylene glycol, 4. Maleimide, 5. Diaminohexane, 6. Ethylene gylcol. (adapted from Kambhampati, 2006 [36]).
Figure 12.4: Reaction scheme for preparing a hydrogel dextran matrix. (adapted from Kambhampati, 2006 [36])
Figure 12.5: Immobilization techniques for fabrication of DNA microarrays (Reprinted from [88] with kind permission from MDPI).
Figure 12.6: DNA immobilization on Au (gold) surface. (Reprinted from [88] with kind permission from MDPI).
Figure 12.7: DNA immobilization by streptavidin-biotin interaction (Reprinted from [88] with kind permission from MDPI)
Figure 12.8: Immobilization of DNA using nanocones. (Reprinted from [88] with kind permission from MDPI)
Figure 12.9: Antigen/antibody interaction.
Figure 12.10: Sensing using direct fluorescence labelling (Reprinted from [27] with kind permission from The American Association for Cancer research).
Figure 12.11: Schematic of ELISA.
Figure 12.12: Different immobilization techniques for fabricating antibody microarrays (a) DNA directed immobilization; (b) Direct spotting; (c) Streptavidin/Biotin linked antibody. (Reprinted from [103] with kind permission from Elsevier)
Figure 12.13: Methods of surface coatings used for antibody and protein microarrays [106].
Figure 12.14: Diagram for detection limits of different surface materials for antibody microarrays. (Reprinted from [73] with kind permission from Elsevier).
Figure 12.15: Schematic representation of antibody immobilization (a) Crystal structure and diagram of an antibody: antibody Fc (protein antigen binding) and Fab (fragment antigen binding) regions, carbohydrates, disulfide bridges, and antigen binding sites are indicated. (b) Random orientation of antibodies on solid, perfect orientation and antibody-binding protein-mediated orientation. (c) DNA assisted antibody immobilization and recombinant antibody immobilization. (Reprinted from [111] with kind permission from Royal Society of Chemistry)

Chapter 13

Figure 13.1: Clinical images showing secondary caries lesions around several composite restorations. The tooth-colored restorations are represented by dash-dot line area.
Figure 13.2: Schematic illustration showing biofilm growth over dental resin composite/tooth surfaces that leads to a negative series of events that may promote the clinical signals (demineralized/ cavited areas) of caries formation around restorations. The biofilm formation is thought to proceed in several distinct phases: (a) Salivary constituents of the salivary pellicle formed over the dental enamel play a major role in dental plaque formation. Salivary proteins that adsorb onto enamel surfaces have been suggested as binding sites for oral bacteria. Deposition of a conditioning layer promotes the adhesion of early bacterial colonizers that begin the co-aggregation cascade. (b) Upon sugar exposure and fermentation, bacteria such as Streptococcus mutans, Lactobacillus acidophilus, Actinomyces viscosus, Nocardia spp., and Candida albicans are able to produce acids and survive in acidic environments. This condition produces a potential cariogenic biofilm able to promote the demineralization of the tooth around restorations.
Figure 13.3: Chemical structure of common components in primers, adhesives and composites and the illustration of the sequence of application for composite restoration placement. Abbreviations: HEMA-hydroxyethyl methacrylate, TEGDMA-triethylene glycol dimethacrylate, BisGMA-bisphenol A glycidyl dimethacrylate.
Figure 13.4: Extracted tooth image showing; (a) Secondary caries occurring at the gap (arrows) between dental hard tissues and restorative materials where oral bacteria exist as biofilm and (b) Scanning electron microscopy image of 48-hour-old in vitro microcosm biofilms visualized over the surface of restorative materials. (The image shows filamentous non-streptococci and streptococci highlighted by arrows).
Figure 13.5: (a) Schematic representation of general chemical structure of quaternary ammonium compounds followed by the sequence of events that describes the mechanism of action of QAMs; (b) Agents binding to cell membranes by ionic and/or hydrophobic interactions, (c) Due to the presence of anionic groups (e.g. carboxyl and phosphate) in their membranes, most microorganisms have a negative surface charge under physiological conditions and react with positively charged biocides, such as QAMs and (d) damage to membrane integrity that leads to bacteria death.
Figure 13.6: (a) and (b): Chemical structures of the most commonly used non-immobilized antibacterial agents incorporated into monomers and (c) chemical structure of the first antibacterial monomer (MDPB) commercialized for dental application.
Figure 13.7: Synthesis of quaternary ammonium monomers (QAMs) with various alkyl chain lengths (CL). (a) Reaction scheme. The alkyl chain has the form of -(CH₂-) which repeats n times and ends with a single CH₃ group. The CL is equal to the number of CH₂ groups (given by n) plus 1 (the CH₃ group). (b) A series of QAMs with various chain lengths synthesized in this study (Reprinted with permission, [78]).
Figure 13.8: S. mutans early attachment and contact-killing effects of antibacterial bonding agents. Images of S. mutans attachment at 4 h on cured resin disks: (a) Scotchbond Multipurpose -SBMP control, (b) SBMP plus 10% of QAM with alkyl chain length CL = 6, (c) CL = 9, (d) CL = 12, (e) CL = 16, and (f) CL = 18. Three disks, with 5 images/disk at random locations, yielded 15 images per group. SBMP with QAM at CL = 16 had the least bacteria colonization. (g) Quantification of resin surface area coverage by bacteria (mean ± SD; n = 15), normalized by bacteria coverage on SBMP control (as 100%). Increasing the CL of QAM greatly decreased bacterial attachment, reaching a minimum at CL = 16 (p < 0.05). Values with dissimilar letters are significantly different from each other (p < 0.05). (Reprinted with permission, ref [78]).
Figure 13.9: Effect of chain length CL on dental plaque microcosm biofilm colonyforming units (CFUs): (a) Total microorganisms, (b) total streptococci, and (c) mutans streptococci. Two-day biofilms on resins were used for CFU measurements (mean ± sd; sample size = 6). Note the log scale for the y-axis. The CFU at CL of 16 was 4 orders of magnitude lower than that of SBMP control. In each plot, values with dissimilar letters are significantly different from each other (p < 0.05). (Reprinted with permission, [80]).
Figure 13.10: Representative live/dead staining images of biofilms adhered to resin disks. (a) SBMP control, (b) 7.5% MPC, (c) 5% DMAHDM, (d) 7.5% MPC+ 5% DMAHDM. The live bacteria were stained green, and the dead bacteria were stained red. SBMP control resin was covered with biofilms consisting of live bacteria. The resin with 7.5% MPC showed much less bacterial adhesion. The resin containing 7.5% MPC+ 5% DMAHDM showed much less bacterial adhesion, and the biofilms consisted of primarily dead bacteria. (Reprinted with permission, [96]).
Figure 13.11: For dentin bond test, 8 teeth were used for each group. Five micro-tensile beams were obtained from each tooth, yielding 40 beams/group. In each plot, values with dissimilar letters are significantly different from each other (p < 0.05).

Chapter 14

Figure 14.1: SEM micrographs showing the topography of non-acid-etched (a) and acid-etched (b) enamel.
Figure 14.2: The molecular structure of Bis-GMA.
Figure 14.3: SEM micrographs of a typical hybrid layer (HL) formed during bonding to dentin (a). Closer view of the HL (b). CR: composite resin; DE: dentin; RT: resin tag; DT: dentinal tubule. Reproduced from [16], with permission.
Figure 14.4: Distinct tissues that comprise the tooth structure: enamel as the most external layer; dentin as the intermediate and bulkiest part of the tooth; and pulp as the most internal layer, which contains nerves and blood vessels.
Figure 14.5: Illustration showing the substrates and materials typically involved in dental adhesion procedures (a); usually, restorative materials (upper surface) will be bonded to teeth or other restorative materials (lower surface). If the upper surface does not show a self-adhesive ability, there will be the need to use an adhesive material to bond the surfaces together (b); however, if the upper surface has a self-adhesive ability, an adhesive will not be necessary (c).
Figure 14.6: Ideal characteristics (principles of adhesion) of adhesives for proper bonding to dental substrates.
Figure 14.7: SEM micrograph of acid-etched dentin showing two dentinal tubules containing remnants of the peritubular dentin matrix. INSET: High magnification of branching collagen fibrils (ca. 75 nm in diameter) separated by interfibrillar spaces that serve as channels for resin infiltration during bonding. Reproduced from [6], with permission.
Figure 14.8: Types of contemporary adhesives following adhesive strategy (etch-and-rinse or self-etch) and the number of clinical application steps (one, two, or three). The “X” represents the absence of the third step in two-step adhesive systems or the absence of the second and third steps in one-step self-etch adhesives.
Figure 14.9: Bonding to dentin using an etch-and-rinse approach. After acid-etching and rinsing procedures, the smear layer is completely removed, exposing the dentin tubules and collagen fibrils; upon primer/adhesive application, a hybrid layer between tooth and composite material is formed. Scheme modified from [7].
Figure 14.10: Scheme showing that the dentin surface must remain moist after etching to prevent exposed collagen fibrils from collapsing (a); otherwise, over-drying of the dentin can cause the exposed collagen fibrils to collapse (b), thus creating an impermeable layer to resin infiltration.
Figure 14.11: Bonding to dentin using a self-etch approach. The self-etching primer is not able to completely remove the smear layer, since it is not rinsed from the surface. As a consequence, the primer and adhesive material are incorporated into the smear layer, so that the hybrid layer formed between tooth and composite material is thinner than that formed using the etch-and-rinse approach. Scheme modified from [7].
Figure 14.12: SEM micrographs of resin-dentin interfaces bonded with Adper Single Bond 2 (3M ESPE), which is a two-step etch-and-rinse adhesive system. Immediately after adhesive application (Control: unmodified adhesive; 2% Minocycline: adhesive modified with 2 wt.% minocycline; and 2% Chlorhexidine: adhesive modified with 2 wt.% chlorhexidine), the amount of silver nitrate penetration, which suggests nanoleakage, was low and practically occurred within the HL (a-c). Few dentin tubules were infiltrated by silver nitrate for all groups (arrows in a-c). After 24 months of water storage, the amount of silver nitrate increased, with silver deposits occurring throughout the entire thickness of the HL and part of the AL, mainly in the control group (arrows in d). RC: resin composite; DE: dentin; HL: hybrid layer; and AL: adhesive layer. Reproduced from [63], with permission.
Figure 14.13: Transmission electron micrograph at 120000× (HV = 80 kV, bar 100 nm) of halloysite aluminosilicate clay nanotubes (Dragonite 1415JM, Applied Minerals Inc., New York, NY, USA).
Figure 14.14: SEM micrographs (a-b) of resin-dentin interfaces obtained from a two-step etch-and-rinse adhesive containing 10 wt.% of nanotubes (NTs). Magnified image (c) showing the presence of NTs on resin tag (RT), i.e., an apparently rougher surface that indicates agglomeration of NTs on RT. CR: composite resin; HL: hybrid layer; DE: dentin; DT: dentinal tubules. Reproduced from [116], with permission.

Chapter 15

Figure 15.1: One of the first bond strength testing devices consisted of six units screwed together into an upper and lower unit. The top and the bottom units were attached to steel wires, in order to make it easier to align the test specimen and avoid premature bond failures. When this device was introduced, a cast gold post (central cylinder) was attached to the two top units, while a “cup” with an embedded dentin disk was secured to the two lower units. The dentin disk was secured to this “cup” with a self-curing resin. The top part of the dentin was machined so a circular dentin cylinder, with the same diameter as the gold post, could contact the gold post. During cementation, cement or resin was placed between the gold and dentin surfaces, which were moved together with a micrometer to produce a predetermined film thickness between dentin surface and gold post.
Figure 15.2: The micro-tensile device developed by Geraldeli [27, 28] uses bonded dentin-composite sticks (1.0 × 1.0 × 6 mm) glued to the device. The two circular units shown in the central part of the figure represent the glue, and between these spheres is the micro-tensile specimen. To stabilize the system, two pins are within the device to guide the movement of the moving parts of the test device and minimize the risk for bending of the test specimen. The two stabilizing pins can be seen in the central slot, adjacent to the test specimen. This slot is machined between the two moving parts to avoid the risk of contaminating the dentin-composite bond region when the test specimen is glued to the device.
Figure 15.3: The shear bond testing device uses a blade. During testing, the blade is pushed against the cylindrical composite specimen bonded to the dentin surface. Rather than using a blade, edge wire loops have also been used around the specimen. When such wires are used, the force is directed upwards rather than downwards as is the case with the blade.
Figure 15.4: Drawings of possible failures of the adhesive joint. Failures a and b represent cohesive failures in the adhesive, failure c represents an interfacial failure, failures d and e represent mixed failures, while failure f represents a combined cohesive failure of the adhesive and the adhered. Of these failures, only failure c is a true adhesion (interface) failure. Cohesive failures occurring in either the composite or the dentin are also common and often included in bond strength results.
Figure 15.5: The figure represents the mean strength values in MPa for Adper SE Plus (dark shaded bars), Adper Single Bond 2 (medium shaded bars), and Scotchbond Multipurpose (light shaded bars) when tested in regular shear (RS), regular tension (RT), micro-shear (MS), and micro-tensile (MT) tests. The standard deviations are shown on the top of each bar. For most of the groups the standard deviations are around 25% of the mean strength values. As seen from the graph, the micro-tensile tests give significantly higher values than the other tests.
Figure 15.6: The bars reveal that shear tests tend to be associated with the largest frequency of adhesion (interface) failures, while cohesive failures are more common for tensile tests. The overall trend is that the test method, rather than specimen size, seems to affect the distribution of different failure types the most.
Figure 15.7: Based on Ingli’s calculations[31], it is possible to determine the stress levels adjacent to the crack tip when a specimen is in tension along the y-axis. The stress level is determined from the height of the flaw (2b) and the depth of the notch (c), from which the curvature (p) at the flaw tip can be determined. As seen from this figure, the localized tensile stress, σ_yy, is about six times higher in front of the flaw tip compared to the tensile stress, σ, applied to the entire specimen in the same direction. The σ_xx value represents a tensile stress in the x direction.
Figure 15.8: Energetics of Griffith crack in uniform tension showing that as the size of the crack increases, the surface energy (S) increases. At the same time, the strain energy (U) decreases. The sum of these two energy values (S + U) is shown by the solid line, and as seen from that curve, the energy of the system increases initially with the flaw size until it reaches the critical flaw size (a_c), whereupon the energy decreases. Thus, before the flaw has reached a_c, it would prefer to heal if given that option, while after exceeding a_c it propagates spontaneously.
Figure 15.9: “a” represents a Class V cavity in which a composite restoration has shrunk freely during polymerization. The gap between the cavity margin and the restoration represents the shrinkage gap. “b” shows a restoration like the one in “a” that has been bonded to the surrounding cavity wall. The outer hatched line represents the original cavity wall shown in “a”, while the hatched line inside the restoration is the location of the composite margin in “a” before it was stretched. As a result of the polymerization shrinkage, the elastic energy of the tooth (U_MT) as well as the elastic energy of the restorative material (U_MC) balance each other, and represents the mechanical energy, U, in Figure 15.8. In “c” a crack, represented by the dark color, has developed in the cervical region. By allowing this crack to propagate, free surface will be formed, causing the surface energy (S) of the restorative-tooth system to increase. As this flaw size exceeds the critical flaw size (shown as a_c in Figure 15.8), the mechanical energy of the restorative-tooth system will decrease until the restoration has debonded as long as the mechanical energy is high enough to drive crack growth.
Figure 15.10: (a) shows the front of the test specimen. A dentin disk, 7 × 4 × 0.75 mm is embedded in the top composite part of the specimen shown in (a) (front view). (b) shows the side of the specimen. Bonding is performed by placing a stainless steel sheet, 0.075 mm thick, covering the top specimen half with its dentin disk. Adhesive is then placed on the chevron shaped exposed dentin surface (light colored field in (c)), and second half of the specimen is made in a mold. After completion, the steel sheet is removed. Test performed at a rate of 0.5 mm/min.
Figure 15.11: Shear bond strength values for Group A (light dotted line) ranged from 12 MPa to 38 MPa, while for group B (dark dotted line) from 4 MPa to 33 MPa. The values were rather evenly distributed within these strength limits for the two groups. The critical stress (C) is the value determined from Hansen and Asmussen’s publication [51].
Figure 15.12: Survival plots of the results generated by Group A (dark dotted line) and Group B (light dotted line) in Figure 11. As seen from the two curves, Group A’s curve has a steeper central part than Group B’s curve. This means that Group A has a higher Weibull modulus, which is associated with less product variations within the test group.

Scrivener Publishing
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Adhesion and Adhesives: Fundamental and Applied Aspects

The topics to be covered include, but not limited to, basic and theoretical aspects of adhesion; modeling of adhesion phenomena; mechanisms of adhesion; surface and interfacial analysis and characterization; unraveling of events at interfaces; characterization of interphases; adhesion of thin films and coatings; adhesion aspects in reinforced composites; formation, characterization and durability of adhesive joints; surface preparation methods; polymer surface modification; biological adhesion; particle adhesion; adhesion of metallized plastics; adhesion of diamond-like films; adhesion promoters; contact angle, wettability and adhesion; superhydrophobicity and superhydrophilicity. With regards to adhesives, the Series will include, but not limited to, green adhesives; novel and high-performance adhesives; and medical adhesive applications.

Series Editor: Dr. K.L. Mittal
1983 Route 52,
P.O. Box 1280, Hopewell Junction, NY 12533, USA
Email: usharmittal@gmail.com

Publishers at Scrivener
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This edition first published 2017 by John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA and Scrivener Publishing LLC, 100 Cummings Center, Suite 541J, Beverly, MA 01915, USA © 2017 Scrivener Publishing LLC
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Library of Congress Cataloging-in-Publication Data
Names: Mittal, K. L., 1945- editor. | Etzler, F. M. (Frank M.), editor.
Title: Adhesion in pharmaceutical, biomedical and dental fields / edited by K. L. Mittal and F. M. Etzler.
Description: Beverly, MA : Scrivener Publishing ; Hoboken, NJ : John Wiley & Sons, 2017. | Series: Adhesion and adhesives : fundamental and applied aspects | Includes index. |
Identifiers: LCCN 2017015278 (print) | LCCN 2017018821 (ebook) | ISBN 9781119323785 (pdf) | ISBN 9781119323792 (epub) | ISBN 9781119323501 (cloth)
Subjects: LCSH: Adhesives. | Biomedical materials. | Pharmaceutical industry–Technological innovations. | Dental bonding.
Classification: LCC TA455.A34 (ebook) | LCC TA455.A34 A33 2017 (print) |
DDC 610.28/4–dc23
LC record available at https://lccn.loc.gov/2017015278

Preface

The phenomenon of adhesion is of cardinal importance in the pharmaceutical, biomedical, and dental fields. A few eclectic examples will suffice to underscore the importance/relevance of adhesion in these three areas. For example, the adhesion between powdered solids is of crucial importance in tablet manufacture. A mundane example is the bandage where the role of adhesion in its performance (sticking and peeling) is all too familiar. The interaction between biodevices (e.g., stents, bio-implants) and body environment governs the performance of such devices, and there is burgeoning research activity in modifying the surfaces of such implements to render them compatible with bodily components. Essentially, there are two distinct approaches which are exploited in this vein: one is to modify the surface chemistry of biodevices by a host of techniques ranging from simple to very sophisticated (e.g., laser treatment) and the second is to deposit suitable coatings. Irrespective of the intended function of the coating, it must adhere to the substrate; so many schemes have been devised to obtain adequate adhesion. The topic of microbial adhesion and biofouling is of grave concern with wide-ranging implications. In the field of dentistry, there has been paradigm shift from retaining of restorative materials by mechanical interlocking to adhesive bonding; so the mantra “adhesive bonding dentistry” has gained much popularity. Those who wear dentures very well know the importance of adhesion. If dentures come out in a social setting, it can be very embarrassing. In the recent past, there has been much activity in ameliorating the existing adhesives or in formulating stronger and better adhesives.

This unique book addresses all these three areas in an easily accessible single source. The impetus for bringing out this compilation stemmed from the lack of a book dealing primarily and specifically with the adhesion aspects in these three areas. So this book was conceived with the express intention to fill this lacuna in the literature.

The book contains 15 chapters written by internationally-renowned subject matter experts and is divided into four parts: Part 1: General Topics; Part 2: Adhesion in Pharmaceutical Field; Part 3: Adhesion in Biomedical Field; and Part 4: Adhesion in Dental Field. The topics covered include: theories or mechanisms of adhesion; wettability of powders; role of surface free energy in tablet strength and powder flow behavior; mucoadhesive polymers for drug delivery systems; transdermal patches; skin adhesion in long-wear cosmetics; factors affecting microbial adhesion; biofouling and ways to mitigate it; adhesion of coatings on surgical tools and bio-implants; adhesion in fabrication of microarrays in clinical diagnostics; antibacterial polymers for dental adhesives and composites; evolution of dental adhesives; and testing of dental adhesive joints.

Kash Mittal
P.O. Box 1280
Hopewell Jct., NY 12533
E-mail: usharmittal@gmail.com

Frank M. Etzler
LECOM
Erie, PA 16509
E-mail: fetzler@Lecom.edu
April 2017