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 Young's 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).

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 Young's 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 Young's modulus. Since polymer crystallinity affects mechanical properties, the effect of increases in crystallinity during degradation on Young's modulus is also considered. To demonstrate the ability of the Effective Cavity Theory, it was fitted to several sets of experimental data for Young's modulus in the literature.

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.

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.

ABC's of bioabsorption: application of lactide based polymers in fully resorbable cardiovascular stents.

Lactide based polymers present a promising class of materials for successful development of fully resorbable stents, thus helping to bring the concept of vascular restoration therapies to life. Not only can these polymers be perfectly tuned to fulfil technical requirements for a fully resorbable stent, they have been proven to be safe materials with a long track record of in vivo biocompatibility in a broad range of medical and pharmaceutical fields. They have a strong regulatory history as well. The polymers degrade through hydrolysis, and are eliminated by the human body through natural pathways via the Krebs cycle. The polymers can perform a temporary mechanical function, allowing the tissue to heal and resume its original function before the implant looses its mechanical integrity. The mechanical performance of the stent can be achieved through stent design and manufacturing methods, as well as tailoring the properties of the polymer itself. The resorption time of cardiovascular stents based on these polymers can be tuned -from a polymer perspective- by tailoring the molecular weight, the crystallinity and the hydrophilicity of the polymer. Drug eluting coatings for resorbable stents can be developed from the same family of polymers, tailoring the composition to the desired controlled release of the applicable drug. To successfully develop resorbable cardiovascular devices an interdisciplinary approach is needed, bringing together polymer chemists and engineers and connecting them with medical device and clinical experts.

Influence of spinline stress on release properties of a coaxial controlled release device based on EVA polymers.

PURPOSE: To investigate the influence of the extrusion parameters on the polymeric structure and release properties of polyethylene vinyl acetate (EVA) coaxial fibers, used for controlled release of steroids. METHODS: Coaxial fibers were prepared under various extrusion conditions. Both spinline stress and release properties were determined. The polymeric structure of the membrane was investigated with wide angle X-ray scattering (WAXS). RESULTS: Upon leaving the spinneret, the polymeric fiber exhibits a large die swell. As a consequence, it is necessary to apply a force to draw the fiber to its desired diameter. A larger drawing force is needed at lower extrusion temperature, at a smaller air gap, or at a higher spinning velocity. It was found that the release rate of a steroid from the coaxial fiber increases, when the fibers are prepared at a higher spinline stress. X-ray measurements reveal that at higher spinline stress, the crystalline volume fraction of the membrane decreases. As a result of a decreasing crystallinity, the permeability of the polymer increases. CONCLUSIONS: It is demonstrated that the extrusion parameters and spinline stress have a significant influence on the polymeric structure of the membrane and hence the release properties. Higher spinline stress results in a higher release rate.

Stability of radiopaque iodine-containing biomaterials.

Stability tests have been performed on two typical iodine-containing radiopaque poly(methacrylate) copolymers. Material A is a terpolymer of methylmethacrylate (MMA), 2-hydroxyethyl methacrylate (HEMA) and 2-[4-iodobenzoyl]-oxo-ethylmethacrylate (4-IEMA); material B is a copolymer of MMA and 4-IEMA. Cylindrical specimens of material A were implanted subcutaneously and intraperitoneally in Wistar rats. The implants were retrieved after 2 years. Histology showed that the material was well-tolerated. Detailed analysis of the surface of the implants by electron spectroscopy for chemical analysis (ESCA) revealed that the material remained stable. No differences could be detected between the ESCA spectra of the explants, and those of the control specimens, which were from the same synthetic batch and which were stored in dry form during the entire experimental period. Material B was also stable upon irradiation with X-rays in vitro, even at high doses, compared to the clinical situation. Exposure of material B to gamma-radiation, however, was found to lead to structural degradation. This was evident from clear yellowing, and also from the ESCA spectra. The spectra revealed that material B deteriorates during gamma-irradiation through rupture of C-C and or C-O chemical bonds, not via C-I bond disruption. It can be concluded that iodine is tightly bound to these radiopaque biomaterials. This is important with regard to potential applications of these materials as implant biomaterials.