Fraser Buchanan

Degradation of poly-L-lactide. Part 1: in vitro and in vivo physiological temperature degradation

Abstract Poly-L-lactide (PLLA) is one of the most significant members of a group of polymers regarded as bioresorbable. The degradation of PLLA proceeds through hydrolysis of the ester linkage in the polymers backbone and is influenced by the polymers initial molecular weight and degree of crystallinity. To evaluate its degradation PLLA pellets were processed by compression moulding into tensile test specimens and by extrusion into 2 mm diameter lengths of rod, prior to being sterilized by ethylene oxide gas (EtO) and degraded in both in vitro and in vivo environments. On retrieval at predetermined time intervals, procedures were used to evaluate the materials molecular weight, crystallinity, mechanical strength, and thermal properties. Additionally, the in vivo host tissues biological response was analysed. The results from this study suggest that in both the in vitro and in vivo environments, degradation proceeded at the same rate and followed the general sequence of aliphatic polyester degradation, ruling out enzymes contributing and accelerating the degradation rate in vivo. Additionally, the absence of cells marking an inflammatory response suggests that the PLLA rods investigated in vivo were biocompatible throughout the 44 weeks duration of the study, before any mass loss was observed.

Printability of calcium phosphate: calcium sulfate powders for the application of tissue engineered bone scaffolds using the 3D printing technique.

In this study, calcium phosphate (CaP) powders were blended with a three-dimensional printing (3DP) calcium sulfate (CaSO4)-based powder and the resulting composite powders were printed with a water-based binder using the 3DP technology. Application of a water-based binder ensured the manufacture of CaP:CaSO4 constructs on a reliable and repeatable basis, without long term damage of the printhead. Printability of CaP:CaSO4 powders was quantitatively assessed by investigating the key 3DP process parameters, i.e. in-process powder bed packing, drop penetration behavior and the quality of printed solid constructs. Effects of particle size, CaP:CaSO4 ratio and CaP powder type on the 3DP process were considered. The drop penetration technique was used to reliably identify powder formulations that could be potentially used for the application of tissue engineered bone scaffolds using the 3DP technique. Significant improvements (p<0.05) in the 3DP process parameters were found for CaP (30-110 μm):CaSO4 powders compared to CaP (<20 μm):CaSO4 powders. Higher compressive strength was obtained for the powders with the higher CaP:CaSO4 ratio. Hydroxyapatite (HA):CaSO4 powders showed better results than beta-tricalcium phosphate (β-TCP):CaSO4 powders. Solid and porous constructs were manufactured using the 3DP technique from the optimized CaP:CaSO4 powder formulations. High-quality printed constructs were manufactured, which exhibited appropriate green compressive strength and a high level of printing accuracy.

Interlaboratory Reproducibility of Standard Accelerated aging Methods for Oxidation of UHMWPE

During accelerating aging, experimental uncertainty may arise due to variability in the oxidation process, or due to limitations in the technique that is ultimately used to measure oxidation. The purpose of the present interlaboratory study was to quantify the repeatability and reproducibility of standard accelerated aging methods for ultra-high molecular weight polyethylene (UHMWPE). Sections (200 microm thick) were microtomed from the center of an extruded rod of GUR 4150 HP, gamma irradiated in air or nitrogen, and circulated to 12 institutions in the United States and Europe for characterization of oxidation before and after accelerated aging. Specimens were aged for 3 weeks at 80 degrees C in an air circulating oven or for 2 weeks at 70 degrees C in an oxygen bomb (maintained at 503 kPa (5 atm.) of O2) in accordance with the two standard protocols described in ASTM F 2003-00. FTIR spectra were collected from each specimen within 24 h of the start and finish of accelerated aging, and oxidation indices were calculated by normalizing the peak area of the carbonyl region by the reference peak areas at 1370 or 2022 cm(-1). The mean relative interlaboratory uncertainty of the oxidation data was 78.5% after oven aging and 129.1% after bomb aging. The oxidation index measurement technique was not found to be a significant factor in the reproducibility. Comparable relative intrainstitutional uncertainty was observed after oven aging and bomb aging. For both aging methods, institutions successfully discriminated between air-irradiated and control specimens. However, the large interinstitutional variation suggests that absolute performance standards for the oxidation index of UHMWPE after accelerated aging may not be practical at the present time.

Designs from the deep: marine organisms for bone tissue engineering.

Current strategies for bone repair have accepted limitations and the search for synthetic graft materials or for scaffolds that will support ex vivo bone tissue engineering continues. Biomimetic strategies have led to the investigation of naturally occurring porous structures as templates for bone growth. The marine environment is rich in mineralizing organisms with porous structures, some of which are currently being used as bone graft materials and others that are in early stages of development. This review describes the current evidence available for these organisms, considers the relative promise of each and suggests potential future directions.

Interlaboratory studies to determine optimal analytical methods for measuring the oxidation index of UHMWPE

Fourier transform infrared spectroscopy has emerged as the technique of choice for the quantification of oxidation in ultra-high molecular weight polyethylene used in orthopedic implants. We initiated interlaboratory studies to determine the method of normalization, hence quantification, that provided the highest level of reproducibility across multiple institutions. The goal of this research was to identify optimal normalization methods that minimize the experimental uncertainties associated with interlaboratory reproducibility and intralaboratory repeatability of oxidation index measurements. Test samples were prepared from GUR 4150 HP, gamma irradiated in air, and had a shelf age of two years. Samples were analyzed according to ten oxidation index test methods during two interlaboratory studies, which were conducted in accordance with ASTM E691. Variations in reproducibility and repeatability were evaluated using analysis of variance (ANOVA). The basis of the test methods (peak area-based vs. peak height-based), as well as the normalization method, were both found to be associated with significant differences in reproducibility (p = 0.0006 andp < 0.0001, respectively). Normalization techniques based on the 1370 and 2022cm(-1) peaks areas were found to be the most reproducible methods, and were associated with mean interlaboratory uncertainties of 16.5% and 24.2%, respectively. Repeatability of the test methods was not sensitive to the normalization technique; the mean intralaboratory repeatability for all of oxidation index measurements was found to be 10.2%. The results of this interlaboratory research will be a useful basis for the development of a new oxidation index standard for the orthopedics community.

Influence of packaging conditions on the properties of gamma-irradiated UHMWPE following accelerated ageing and shelf ageing

The ageing behaviour of ultra-high molecular weight polyethylene (UHMWPE) has been studied following gamma irradiation (25 or 40 kGy) in air or in inert atmosphere (vacuum packed). Accelerated ageing procedures used elevated temperature (70 degrees C) and/or pressurised oxygen (5 bar). Shelf ageing for up to six months was also performed. The variation in polymer properties with depth into the polymer was determined using density measurements, infra-red spectroscopy and differential scanning calorimetry. Tensile properties of the irradiated polymer after accelerated ageing were also determined. Accelerated ageing in air for 20 days or pressurised oxygen for 4 days resulted in peaks in polymer density, crystallinity and degree of oxidation at the polymer surface. Accelerated ageing in pressurised oxygen for 8 days resulted in peaks in these properties 500 microns below the polymer surface. Where gamma irradiation was performed in inert atmosphere the amount of polymer degradation following accelerated ageing (in oxidising conditions) was generally lower but still significant. Differences were also observed in tensile properties between material gamma-irradiated in air and in vacuum. This study indicated that performing gamma sterilisation procedures under inert conditions can reduce the level of UHMWPE degradation when exposed to an oxidising environment.

The influence of gamma irradiation and aging on degradation mechanisms of ultra-high molecular weight polyethylene.

The aging behavior of ultra-high molecular weight polyethylene (UHMWPE) has been studied following gamma irradiation in air. Accelerated aging procedures used elevated temperature (70 °C), pressurized oxygen (5 bar) and applied stress. Shelf and in vivo aged components have also been investigated. The variation in polymer properties with depth into the polymer was determined using density measurements, infra-red spectroscopy and differential scanning calorimetry. Accelerated aging in pressurized oxygen resulted in peaks in polymer density and degree of oxidation up to 500 μm below the polymer surface. Shelf and in vivo aging was also found to result in increased density at or below the component surfaces. Changes in density were mainly due to changes in crystallinity within the UHMWPE and, to a smaller extent, due to oxygen incorporation within the polymer. The application of stress did not appear to influence the accelerated aging of UHMWPE. A method for estimating the residual stress distribution in the UHMWPE using the measured changes in density is proposed. This study has indicated that oxidation of UHMWPE may lead to the development of tensile residual stresses, near the component surface, in the region of 1.7 MPa. These stresses may contribute to the failure mechanism of UHMWPE acetabular cups or knee tibial trays during service.

Short-fibre reinforcement of calcium phosphate bone cement.

Abstract Calcium phosphate cement (CPC) sets to form hydroxyapatite, a major component of mineral bone, and is gaining increasing interest in bone repair applications. However, concerns regarding its brittleness and tendency to fragment have limited its widespread use. In the present study, short-fibre reinforcement of an apatitic calcium phosphate has been investigated to improve the fracture behaviour. The fibres used were polypropylene (PP) fibres, 50 μm in diameter and reduced in length by cryogenic grinding. The compressive strength and fracture behaviour were examined. Fibre addition of up to 10 wt% had a significant effect on composite properties, with the energy absorbed during failure being significantly increased, although this tended to be accompanied with a slight drop in compressive strength. The fibre reinforcement mechanisms appeared to be crack bridging and fibre pull-out. The setting time of the CPC with fibre reinforcement was also investigated and was found to increase with fibre volume fraction.

Surface modification of poly(e-caprolactone) using a dielectric barrier discharge in atmospheric pressure glow discharge mode

The role of roughening and functionalization processes involved in modifying the wettability of poly(epsilon-caprolactone) (PCL) after treatment by an atmospheric pressure glow discharge plasma is discussed. The change in the ratio of CO/C-O bonds is a significant factor influencing the wettability of PCL. As the contact angle decreases, the level of CO bonds tends to rise. Surface roughness alterations are the driving force for lasting increases in wettability, while the surface functional species are shorter lived. We can approximate from ageing that the increase in wettability for PCL after plasma treatment is 55-60% due to roughening and 40-45% due to surface functionalization for the plasma device investigated.

Development of a bovine collagen-apatitic calcium phosphate cement for potential fracture treatment through vertebroplasty.

The aim of this study was to examine the potential of incorporating bovine fibres as a means of reinforcing a typically brittle apatite calcium phosphate cement for vertebroplasty. Type I collagen derived from bovine Achilles tendon was ground cryogenically to produce an average fibre length of 0.96±0.55 mm and manually mixed into the powder phase of an apatite-based cement at 1, 3 or 5 wt.%. Fibre addition of up to 5 wt.% had a significant effect (P ≤ 0.001) on the fracture toughness, which was increased by 172%. Adding ≤ 1 wt.% bovine collagen fibres did not compromise the compressive properties significantly, however, a decrease of 39-53% was demonstrated at ≥ 3wt.% fibre loading. Adding bovine collagen to the calcium phosphate cement reduced the initial and final setting times to satisfy the clinical requirements stated for vertebroplasty. The cement viscosity increased in a linear manner (R²=0.975) with increased loading of collagen fibres, such that the injectability was found to be reduced by 83% at 5 wt.% collagen loading. This study suggests for the first time the potential application of a collagen-reinforced calcium phosphate cement as a viable option in the treatment of vertebral fractures, however, issues surrounding efficacious cement delivery need to be addressed.