Adhesives and sealants in medicine, dentistry and pharmacy - a review of materials and applications - Part II

TWI Bulletin, March/April 2002

Mehdi Tavakoli received a BSc in Chemistry and an MSc and PhD on Polymer Science and Technology at Aston University in Birmingham. He joined TWI in 1989 and has been working on new joining and associated technologies with particular interest in joining and coating of medical and implantable devices. He has over 20 years research, industrial problem solving and product development experience on polymeric materials and has published more than 40 papers and patents and is currently working as Technology Manager on polymers/adhesives at TWI.

The first episode of Mehdi Tavakoli's review of materials and applications in adhesives and sealant in medicine dealt with joining tissue, muscle and bone. Part two continues the story with examination of TWI's work on dental and pharmaceutical adhesives.

The areas of tooth which will be in contact with the adhesives are enamel or the underlying dentine. The main structure of tooth is based on dentine which consists of 69% calcium hydroxyapatite, 18% collagen and water. Dentine is covered with enamel which consists of 96% hydroxyapatite.

The main critical issues which affect the performance of dental adhesives are similar to the main factors affecting non-dental bonding applications:

• Reactivity of adhesives - includes chemical ( eg primary and secondary chemical bonding) and physical (wetting, penetration into surface irregularities) reactivities between the adhesive and the tooth ( eg dentine and enamel) surfaces.
• Surface condition of tooth - chemical and physical surface conditions of the enamel and dentine can affect adhesion of dental material and long-term durability. The presence of surface contamination, such as debris (generated as a result of drilling and cutting operations), saliva or wear surface layers ( eg incomplete removal of caries) can lead to a weak interface between the dental material and tooth. This can lead to penetration of moisture and fluids to the interfacial regions and premature failure of restorative or decorative materials.
• Mismatch of thermal or fluid expansion properties between dental materials and tooth can cause residual stress which can lead to premature failure.
• Shrinkage of adhesives during or after the curing reactions can cause disbonding and premature failure.
• Insufficient cure - lack of complete cure or setting of the polymeric resins can cause formation of a weak protective or filling material which will be susceptible to premature degradation and failure. Nowadays almost all adhesives in restorative dentistry are based on visible light-curing polymeric resins. Incomplete curing of these material ( eg due to short cure times, insufficient radiation energy or shadowing effect in thick section fillings) can produce fillings with low cohesive strength, low adhesion which are prone to microcracking, debonding and deterioration.

Polymeric adhesives and composites used in dentistry are generally based on combinations of acrylate/bioacrylate or methacrylate multifunctional monomers, activators, adhesion promoters and fillers. Curing and polymerisation of these resins take place through a free radical chain mechanism in the presence of initiators. Typical initiators or activators used in these formulations include redox systems ( ie a reducing agent ( eg an aromatic amine) and an oxidising agent place throug peroxides, such as BPO) or a photo-initiator for light curing polymerisation. New generations of dental adhesives can provide high bond strength (15-25MPa) to dentine or enamel. Recently the use of photochemically ( eg use of blue light, l = 470nm) activated dental adhesives has considerably replaced the chemically activated systems. Avoiding oxygen inhibition of the curing process, improving mechanical properties and long term durability, and better adhesion to various surfaces of dental adhesives are still areas of research.

Development of a new type of high impact strength dental polymeric resins has been achieved by using reinforcing effects of acrylic-terminated butadiene-styrene block copolymers for modification of polymethylmethacrylate polymers.

Another important class of materials is based on glass ionomer systems. These are used as an aesthetic restorative filling and as core build up materials in dentistry. The main components of these conventional cements are: ^[25]

• Fluoroaluminosilicate (FAS) glass powder
• Ionic poly mer which is a polycarboxylic acid
• Tartaric acid
• Water

These are formulated to provide a powder and a liquid portion which are mixed under a chemical reaction to provide a set cement. The original glass ionomer suffered from a number of disadvantages: brittleness and susceptibility to early moisture contamination, short working time and long set time. These disadvantages led to the development of light curing glass ionomer cements for dentistry. The curing reactions of light cure glass ionomers are shown in Fig.7.

Two types of reaction take place:

• The acid groups of the polymer attack the FAS glass releasing positively charged ions. These ions react with the carboxylic acid groups of the polymer in an acid-base curing reaction. A very important by-product of this curing reaction is the sustained release of fluoride ions which are known to provide caries resistance and prevent tooth decay. The acid-base reaction can continue indefinitely and therefore the release of fluoride also continues for prolonged periods in a consistent manner.
• A light activated free radical polymerisation of methacrylate groups of the polymer and HEMA (2-hydroxyethylmethacrylate). The rate of this reaction is much faster than the first set of reactions.

However, light curing glass-ionomers also suffer from limitations in depth of cure, which means that time-consuming and complicated layer by layer curing is required when thicker sections are used. This led to the development of a new generation of Vitremer tri-cure glass ionomer systems. ^[25] Vitremer can, under a third mode of cure, ensure complete setting in deeper sections and shadowed areas. The Vitremer tri-cure system is shown in Fig.8.

The third reaction is a dark cure of the methacrylate groups of the polymer systems and HEMA. The relatively fast cure is initiated by a water-activated redox catalyst ^[26] which enables the methacrylate cure to occur in the dark. This is a unique feature of Vitremer tri-cure based materials producing uniform cure throughout the glass ionomer restoratives, resulting in enhanced physical properties even in thick sections.

Another area of adhesives use in dentistry is for fixing dentures. There are a wide range of denture adhesives which are available commercially. ^[27] Typical examples are shown in Table 4. Denture adhesives are available in the form of liquids, creams and powders and the active ingredients of many of them are based on one or more of the following constituents:

• Gum karaya
• Polyethylene oxide
• Sodium carboxymethyl cellulose
• Sodium alginate

Pharmaceutical polymers and adhesives

• Pharmaceutical grade
• Unable to produce extractable species
• Chemically inert
• Easily processable
• Suffer minimal undesirable ageing

• Polyethylene glycol
• Polyacrylic acid
• Polyvinyl alcohol
• Polymethacrylic acid
• Polyacrylamide
• Poly N-vinyl-pyrrolidone

• Polyorthoesters
• Polylactides
• Polyglicolides
• Polyanhydrides

As a result of biodegradation these polymers are broken down into biologically acceptable molecules that are metabolised and removed from the body via normal metabolic pathways.

One of the most important classes of synthetic polymers used in pharmaceutical applications is based on acrylic resin systems. ^[29-30] Specific grades of acrylic polymers have been used, or considered for use, in many pharmaceutical applications such as drug delivery systems, as a container to deliver drugs or as coatings. These applications include gastro-intestinal, epidermal, transdermal, nasal, ocular drug delivery systems or as hydrogels. These polymers are primarily based on acrylic acids, methacrylic esters or acrylic resins. The chemical structure and composition of the most commonly known grades are shown in Tables 5 and 6. ^[29]

Work carried out at TWI has shown that welding and adhesive bonding can be used effectively for joining and sealing pharmaceutical polymers.

Typical examples of pH dependent commercially available acrylic polymers are shown in Table 7. These polymers are designed to be activated in different pH environments of the gastro intestinal system, see Fig.9.

Concluding remarks

It should be noted that many critical issues for the use of adhesives and polymers in medicine, dentistry and pharmacy are also of significant importance to adhesion scientists and technologists. For example, the surface characteristics of the skin (eg wet, dry, soft or fragile) or surface condition of a tooth is as critical as in tissue bonding or dentistry as the surface properties of metallic or non-metallic adherends used in non-medical ( eg automotive and aerospace) bonding applications. Surface pretreatments and the use of primers and adhesion promoters can also play a major role in both of these cases. Other major issues which are shared by some of the medical and non-medical uses of polymers include mechanisms of adhesion, the nature and strength of interfaces, mechanisms of biodegradation as well as the nature of degradation products.

Many other factors relevant to medical use of adhesives and bone cements can also be related to non-medical applications, for example; low exothermic polymerisation reactions, purity of the polymeric resins, low or non release of monomers or other volatiles during or after cure, good mechanical properties, low shrinkage and low creep, rapid cure after dispensing and improved adhesion. These plus a level of durability and reliability are of critical importance to opto and micro-electronic use of adhesives.

It is believed that a multi-disciplinary approach and utilisation of relevant issues from non-medical use of polymers, adhesives, sealants or coatings can significantly improve progress in medical applications of polymers. Many common issues relevant to materials development, joining techniques, degradation mechanisms and surface and interface assessment techniques can be successfully utilised from industrial applications to the medical sector.

Based on these facts TWI is actively working with clinicians, hospitals and well known biomaterials groups to study some of the most fundamental issues related to these areas.

Acknowledgements

The author wishes to thank Henkel/Loctite UK, 3M UK, Chemence and Degussa UK for providing some of the photographs and information.

Adhesives and sealants in medicine, dentistry and pharmacy - a review of materials and applications - Part I of this report.

References