Brian J. Tighe

A review of biodegradable polymers: uses, current developments in the synthesis and characterization of biodegradable polyesters, blends of biodegradable polymers and recent advances in biodegradation studies

This review considers the uses of biodegradable polymers in terms of their relevance within current plastic waste management of packaging materials, biomedical applications and other uses; research papers and patents are catalogued. The chemical synthesis of polyesters and the microbial production of poly(hydroxyalkanoate)s, including recent publications in these areas, are covered and methods of characterization and structural analysis are outlined. Current research into two- and three-component blends is reviewed as a method of reducing overall costs and modifying both properties and biodegradation rates of materials. Finally, there is a summary of degradation processes. Both abiotic and biotic reactions are discussed, together with the development of biodegradation test methods, particularly with respect to composting.

Polymers for biodegradable medical devices. 1. The potential of polyesters as controlled macromolecular release systems

Abstract Prolonged controlled release of drugs from polymeric matrices is now well established. In contrast, however, release of macromolecules presents more difficulties and in consequence is less well studied and relatively rarely discussed in the literature. The processes of biodegradation and bioerosion which are important in this field have been exploited in other types of surgical device for some years. This review brings together the literature on various aspects of the bioerosion of polymers containing ester groups, with particular emphasis on release and degradation studies that might form a basis for the design and selection of controlled macromolecular release systems. Polymers discussed include the poly(alpha esters) -including poly(lactic acid) and polyfglycolic acid) —, poly(3-hydroxybutyrate), polydioxanes, polyoxalates, polylactones, polyester hydrogels and the polyanhydride/poly(ortho ester) series.

Cellular interactions with synthetic polymer surfaces in culture

The success of synthetic polymers as biomaterials depends upon their interfacial properties and resultant interactions with cells and biological fluids in vivo. A useful experimental approach to defining requirements for biocompatibility is to study the mechanisms by which synthetic substrata influence eukaryote cell behaviour in culture. Here we present an overview of the relationships between physical and chemical substratum properties and cell behaviour on a range of synthetic polymers. We relate our results to theories of in vivo tissue compatibility.

Synthetic hydrogels: 1. Hydroxyalkyl acrylate and methacrylate copolymers - water binding studies

Abstract Copolymers of hydroxyethyl acrylate (HEA), hydroxypropyl acrylate (HPA), hydroxyethyl methacrylate (HEMA) and hydroxypropyl methacrylate (HPMA) with styrene and with methyl methacrylate have been studied. Variations in nature and composition have been correlated, both with the total equilibrium water content of the resultant hydrogel and with the more detailed water binding behaviour as revealed by differential scanning calorimetry studies. Differential scanning calorimetry enables the relative proportions of non-freezing and freezing water to be determined and, in addition, enables the fine structure of the melting endotherm to be observed. Particular interest centres around the ability to produce hydrogels in which all freezing water has been eliminated by progressive incorporation of non-hydrophilic monomer or crosslinking agent (ethylene glycol dimethacrylate). Distinct differences are observed between hydrophilic acrylates and methacrylates in the relative effects of temperature on the equilibrium water contents of their respective copolymer series.

Macroporous hydrogels for biomedical applications: methodology and morphology

Macroporous hydrogel membranes have been fabricated using two complementary techniques, both involving the polymerization of a solution of monomers around a crystalline matrix which is subsequently removed. The first of these is the freeze-thaw technique, in which aqueous systems are used to form ice-based crystalline matrices. Whereas in the second, the porosigen technique, a crystalline compound (e.g. sucrose) is dispersed in the monomer solution prior to polymerization. Both copolymer composition and the polymerization conditions were found to influence membrane morphology and the limitations in the range of morphologies attainable using each technique are discussed. Careful choice of technique and polymerization conditions enables macroporous hydrogels with a wide range of morphologies to be fabricated, which are potentially valuable in a variety of biomedical applications. The suitability of these techniques described for the production of materials for use in affinity chromatography, as cell separation substrates and as synthetic articular cartilage as well as more general areas of biomedicine, is discussed.

Synthetic hydrogels VI. Hydrogel composites as wound dressings and implant materials

An overview is presented of the use of hydrogel composites as biomaterials. These range from laminates or coatings (in which a homogeneous hydrogel is used in conjunction with a more mechanically stable substrate), through blends of hydrogels with synthetic hydrophobic polymers, to the use of two-component systems in which water enhances the compatibility of two structurally different polymers. Although synthetic hydrogels provide an ideal basis for materials of these types, naturally occurring hydrophilic polymers with their unique properties have a major contribution to make. It is in the clinical and patent literature, rather than journals dealing with polymers per se, that the vast majority of examples of the use of hydrogel composites are found. This review collects and comments on examples based on synthetic developments in this field during the last decade, particularly in relation to the development of wound dressings and implant materials.

An in Vivo Comparison of the Kinetics of Protein and Lipid Deposition on Group Ii and Group Iv Frequent-replacement Contact Lenses

Purpose. To investigate the degree and rate of deposition of protein and lipid on FDA group II and group IV contact lens materials over a period of up to 28 days of wear. Methods. Twenty-two subjects wore a group IV lens (Acuvue) and a group II lens (Soflens 66) in a randomized, cross-over study. The lenses were randomly worn for periods between 1 and 28 days and then collected for laboratory-based deposition analysis. Results. The group II lenses revealed an increased degree of lipoidal spoilage (p < 0.0001) and the group IV lenses exhibited increased protein spoilage (p < 0.0001). Surface protein for both materials reached a maximum after 1 day and did not increase over the 4-week wearing period (p = NS). Total protein for group IV lenses reached a maximum between 1 and 7 days and then reached a plateau, with no further increase occurring (p = NS), whereas total protein accumulation on the group II lens continued to increase across all time periods (p < 0.05). Lipid deposition on the group IV lens was maximal after 1 day and increased no further (p = NS), whereas lipid deposition on the group II material monotonously increased and progressively built-up over the 4 weeks of wear (p < 0.0001). Conclusions. The kinetics of contact lens deposition is mediated by the chemical structure of the contact lens material under consideration. Protein deposition occurs rapidly with group IV materials before reaching a maximum, whereas N-vinyl pyrrolidone-containing group II materials progressively accumulate protein and lipid deposits, with no plateau occurring.

The osteo-odonto-keratoprosthesis (OOKP).

The osteo-odonto-keratoprosthesis (OOKP), although described over 40 years ago, remains the keratoprosthesis of choice for end-stage corneal blindness not amenable to penetrating keratoplasty. It is particularly resilient to a hostile environment such as the dry keratinized eye resulting from severe Stevens-Johnson syndrome, ocular cicatricial pemphigoid, trachoma, and chemical injury. Its rigid optical cylinder gives excellent image resolution and quality. The desirable properties of the theoretical ideal keratoprosthesis is described. The indications, contraindications, and patient assessment (eye, tooth, buccal mucosa, psychology) for OOKP surgery are described. The surgical and anaesthetic techniques are described. Follow-up is life-long in order to detect and treat complications, which include oral, oculoplastic, glaucoma, vitreo-retinal complications and extrusion of the device. Resorption of the osteo-odonto-lamina is responsible for extrusion, and this is more pronounced in tooth allografts. Regular imaging with spiral-CT or electron beam tomography can help detect bone and dentine loss. The optical cylinder design is discussed. Preliminary work towards the development of a synthetic OOKP analogue is described. Finally, we describe how to set up an OOKP national referral center.

Polymers for biodegradable medical devices: III. Polymerization and copolymerization of cyclic derivatives of tartronic acid

The syntheses of anhydrosulphite and anhydrocarboxylate derivatives of tartronic acid are described. These compounds, more correctly named 5-carboxy-1,3,2-dioxathiolan-4-one-2-oxide and 5-carboxy-1,3-dioxolan-2,4-dione have been shown to undergo polymerization and copolymerization to poly-alpha-esters containing the tartonic acid residue, characterized by the presence of a pendant carboxyl group. Thermal polymerization of the anhydrosulphite appears to proceed in a substantially identical manner to other members of the series in which the monomer decomposes by a first order process to yield an alpha-lactone which polymerizes by a rapid chain growth reaction. Because the rate of thermal polymerization of tartronic acid anhydrosulphite is much more rapid than simple alkyl substituted anhydrosulphites, copolymerization favours the former residues. More successful copolymerization was achieved by the use of tertiary base initiators and the anhydrocarboxylate derivative of tartronic acid. The polymers and copolymers described are of potential value in the synthesis of drug-carrying biodegradable matrices or more hydrophilic analogues of poly(glycolic acid) which combine the known bioerodibility of the moiety with that presence of a pendant carboxyl group.

Polymers for biodegradable medical devices: VIII. Hydroxybutyrate-hydroxyvalerate copolymers: physical and degradative properties of blends with polycaprolactone

The physical and degradative properties of polyhydroxybutyrate-hydroxyvalerate copolymer blends with polycaprolactone were investigated. Blends containing low levels of polycaprolactone (less than 20%) were found to possess a considerable degree of compatibility, whilst those with higher levels of polycaprolactone were incompatible and showed phase separation behaviour. This incompatibility was most marked in blends containing approximately 50% of each component. In blends containing low levels of polycaprolactone, processing conditions governed the ease of crystallization of polycaprolactone in the polyhydroxybutyrate-hydroxyvalerate matrix and thus the mechanical property of the blend. The degradation rate of these blends was found to be influenced by a complex set of factors, including temperature, pH and polycaprolactone content of the blend. Although crystallinity affected the mechanical properties of the blends, its influence on the hydrolytic degradation rate was masked by the large difference in the molecular weight of the polyhydroxybutyrate-hydroxyvalerate copolymers (MW approximately 300,000) and polycaprolactone. (MW approximately 50,000). The polyhydroxybutyrate-hydroxyvalerate/polycaprolactone blends were found to be much more stable to hydrolytic degradation than polyhydroxybutyrate-hydroxyvalerate/polysaccharide blends previously studied. Here the combined techniques of goniophotometry and surface energy measurements proved extremely valuable in monitoring the early stages of degradation, during which surface, rather than bulk degradation, processes predominate.