Andrew Gleadall

Degradation mechanisms of bioresorbable polyesters. Part 1. Effects of random scission, end scission and autocatalysis.

A mathematical model was developed to relate the degradation trend of bioresorbable polymers to different underlying hydrolysis mechanisms, including noncatalytic random scission, autocatalytic random scission, noncatalytic end scission or autocatalytic end scission. The effect of each mechanism on molecular weight degradation and potential mass loss was analysed. A simple scheme was developed to identify the most likely hydrolysis mechanism based on experimental data. The scheme was first demonstrated using case studies, then used to evaluate data collected from 31 publications in the literature to identify the dominant hydrolysis mechanisms for typical biodegradable polymers. The analysis showed that most of the experimental data indicates autocatalytic hydrolysis, as expected. However, the study shows that the existing understanding on whether random or end scission controls degradation is inappropriate. It was revealed that pure end scission cannot explain the observed trend in molecular weight reduction because end scission would be too slow to reduce the average molecular weight. On the other hand, pure random scission cannot explain the observed trend in mass loss because too few oligomers would be available to diffuse out of a device. It is concluded that the chain ends are more susceptible to cleavage, which produces most of the oligomers leading to mass loss. However, it is random scission that dominates the reduction in molecular weight.

Degradation mechanisms of bioresorbable polyesters. Part 2. Effects of initial molecular weight and residual monomer

This paper presents an understanding of how initial molecular weight and initial monomer fraction affect the degradation of bioresorbable polymers in terms of the underlying hydrolysis mechanisms. A mathematical model was used to analyse the effects of initial molecular weight for various hydrolysis mechanisms including noncatalytic random scission, autocatalytic random scission, noncatalytic end scission or autocatalytic end scission. Different behaviours were identified to relate initial molecular weight to the molecular weight half-life and to the time until the onset of mass loss. The behaviours were validated by fitting the model to experimental data for molecular weight reduction and mass loss of samples with different initial molecular weights. Several publications that consider initial molecular weight were reviewed. The effect of residual monomer on degradation was also analysed, and shown to accelerate the reduction of molecular weight and mass loss. An inverse square root law relationship was found between molecular weight half-life and initial monomer fraction for autocatalytic hydrolysis. The relationship was tested by fitting the model to experimental data with various residual monomer contents.

An atomic finite element model for biodegradable polymers. Part 2. A model for change in Young's modulus due to polymer chain scission.

Atomic simulations were undertaken to analyse the effect of polymer chain scission on amorphous poly(lactide) during degradation. Many experimental studies have analysed mechanical properties degradation but relatively few computation studies have been conducted. Such studies are valuable for supporting the design of bioresorbable medical devices. Hence in this paper, an Effective Cavity Theory for the degradation of Youngs modulus was developed. Atomic simulations indicated that a volume of reduced-stiffness polymer may exist around chain scissions. In the Effective Cavity Theory, each chain scission is considered to instantiate an effective cavity. Finite Element Analysis simulations were conducted to model the effect of the cavities on Youngs modulus. Since polymer crystallinity affects mechanical properties, the effect of increases in crystallinity during degradation on Youngs modulus is also considered. To demonstrate the ability of the Effective Cavity Theory, it was fitted to several sets of experimental data for Youngs modulus in the literature.

Computer Simulation of Polymer Chain Scission in Biodegradable Polymers

Biodegradable polymers are used in medical devices such as fixation plates, sutures, or micro particles for the controlled release of drugs. Typical polymers are poly lactic acid (PLA), poly glycolic acid (PGA), and poly caprolactone (PCL). During degradation, the ester bonds within polymer chains are cleaved due to the hydrolysis reaction in the presence of water. It has been suggested that both chain end scission and random chain scission occur [1] and mathematical models have been able to fit experimental data with assumptions of random scission [2-4], end scission [5], or a combination of both [6]. In random scission, every bond in a polymer chain is assumed to be equally susceptible to hydrolysis. In chain end scission, the final bond in a chain is cleaved resulting in the production of a monomer.

Manufacturing Technology: Micro-machining

Micro-machining technologies have been the subject of many studies and developments over recent decades due to their importance in the production of micro-moulds, micro-valves, medical components, micro-electrical-mechanical-systems, sub-miniature actuators, motors and micro-products generally. This chapter defines some key terms (in the context of micro-machining) and then outlines material considerations, challenges in obtaining the desired surface finish, simulation techniques, process and machine aspects of micro-machining, and it finally provides examples of micro-manufacturing sectors and applications.

Mechanical properties of biodegradable polymers for medical applications

Abstract This chapter presents a review of the mechanical properties of biodegradable polymers and the effects of degradation. The current fundamental theories of elastic and plastic deformation are discussed, and mechanical properties including stiffness, strength, and elongation-at-break are considered in relation to specific experimental examples from the literature. The effects of molecular weight and crystallinity, which both vary greatly during degradation, are analysed. A simple linear relationship between Young’s modulus and log( M n ) is found to fit to a large number of experimental data sets from the literature. Three existing theoretical studies for the degradation of mechanical properties are also reviewed.

An atomic finite element model for biodegradable polymers. Part 1, Formulation of the finite elements

Molecular dynamics (MD) simulations are widely used to analyse materials at the atomic scale. However, MD has high computational demands, which may inhibit its use for simulations of structures involving large numbers of atoms such as amorphous polymer structures. An atomic-scale finite element method (AFEM) is presented in this study with significantly lower computational demands than MD. Due to the reduced computational demands, AFEM is suitable for the analysis of Youngs modulus of amorphous polymer structures. This is of particular interest when studying the degradation of bioresorbable polymers, which is the topic of an accompanying paper. AFEM is derived from the inter-atomic potential energy functions of an MD force field. The nonlinear MD functions were adapted to enable static linear analysis. Finite element formulations were derived to represent interatomic potential energy functions between two, three and four atoms. Validation of the AFEM was conducted through its application to atomic structures for crystalline and amorphous poly(lactide).