Jun Jie Wu

Preparation of emulsion-templated porous polymers using thiol–ene and thiol–yne chemistry

Highly porous polymeric materials are prepared by thiol–ene and thiol–yne mediated network formation using high internal phase emulsion templates. The efficiency of network formation is between 80 and 90% for all materials while the thiol–yne materials display enhanced strength and toughness due to their higher degree of crosslinking.

Degradable emulsion-templated scaffolds for tissue engineering from thiol–ene photopolymerisation

Emulsion templating has been used to prepare highly porous polyHIPE materials by thiol–ene photoinitiated network formation. Commercially available multifunctional thiols and acrylates were formulated into water-in-oil high internal phase emulsions (HIPEs) using an appropriate surfactant, and the HIPEs were photo-cured. The temperature of the HIPE aqueous phase was found to influence the morphology of the resulting materials. In agreement with previous work, a higher aqueous phase temperature (80 °C) gave rise to a larger mean void and interconnect diameter. The influence of temperature on morphology was found to be reduced at higher porosity, but still significant. The Youngs modulus of the porous materials was shown to be related to the functionality of the acrylate comonomer used. A mixture of penta- and hexa-acrylate gave rise to a 100-fold increase in modulus, compared to an analogous tri-functional acrylate. The materials could be functionalised conveniently by addition of mono-acrylates or thiols to the organic phase of the precursor HIPE. Degradation was observed to occur at a rate depending on the degradation conditions. Under cell culture conditions at 37 °C, 19% mass loss occurred over 15 weeks. The scaffolds were found to be capable of supporting the growth of keratinocytic cells (HaCaTs) over 11 days in culture. Some penetrative in-growth of the cells into the scaffold was observed.

Mechanical integrity of compression-moulded ultra-high molecular weight polyethylene: effects of varying process conditions.

Ultra-high molecular weight polyethylene (UHMWPE) bearing surfaces in knee and hip prostheses are frequently manufactured by direct compression moulding of the as-polymerised powder. A study was made of the important role of the temperature-time sequence in the melt state during processing, in determining the mechanical integrity of mouldings at 37 degrees C. Structural features were determined by calorimetry (for the degree of crystallinity), infra-red spectroscopy (for the degree of oxidation), density measurement, and scanning electron microscopy. Mechanical integrity was assessed by tensile tests at a constant nominal strain-rate of 10(-3) s(-1), with post-failure microscopic examination. For the whole range of melt temperatures 145-200 degrees C and times 10-90 min, essentially the same stress-strain path was followed, reflecting invariance of the degree of crystallinity. However, there were dramatic changes in elongation-to-break, from ca 10% for some mouldings at 145 degrees C to a mean of 560% at 175 degrees C where, at the 86% confidence level, there was evidence for a peak. The rise was explained by microscopy, that revealed two distinct types of fusion defect, of reducing severity with increasing temperature. Type 1 defects were voids arising from incomplete powder compaction, and persisted up to 165 degrees C. Type 2 defects were regions of enhanced deformability at inter-particle boundaries in apparently fully compacted mouldings, evidenced microscopically by localised relative displacements at particle interfaces, during the plastic deformation at 37 degrees C. They persisted up to 200 degrees C. Type 2 defects may be attributed to the slow self-diffusion of UHMWPE in the melt, leading to incomplete homogenisation. even after compaction is complete. The level of oxidation in the mouldings was small but rose with melt temperature, explaining the fall in elongation-to-break at temperatures higher than 175 degrees C.

A gradient of matrix-bound FGF-2 and perlecan is available to lens epithelial cells

Fibroblast growth factors play a key role in regulating lens epithelial cell proliferation and differentiation via an anteroposterior gradient that exists between the aqueous and vitreous humours. FGF-2 is the most important for lens epithelial cell proliferation and differentiation. It has been proposed that the presentation of FGF-2 to the lens epithelial cells involves the lens capsule as a source of matrix-bound FGF-2. Here we used immunogold labelling to measure the matrix-bound FGF-2 gradient on the inner surface of the lens capsule in flat-mounted preparations to visualize the FGF-2 available to lens epithelial cells. We also correlated FGF-2 levels with levels of its matrix-binding partner perlecan, a heparan sulphate proteoglycan (HSPG) and found the levels of both to be highest at the lens equator. These also coincided with increased levels of phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2) in lens epithelial cells that localised to condensed chromosomes of epithelial cells that were Ki-67 positive. The gradient of matrix-bound FGF-2 (anterior pole: 3.7 ± 1.3 particles/μm2; equator: 8.2 ± 1.9 particles/μm2; posterior pole: 4 ± 0.9 particles/μm2) and perlecan (anterior pole: 2.1 ± 0.4 particles/μm2; equator: 5 ± 2 particles/μm2; posterior pole: 1.9 ± 0.7 particles/μm2) available at the inner lens capsule surface was measured for the bovine lens. These data support the anteroposterior gradient hypothesis and provide the first measurement of the gradient for an important morphogen and its HSPG partner, perlecan, at the epithelial cell-lens capsule interface.

Processing of Ultra-High Molecular Weight Polyethylene: Modelling the Decay of Fusion Defects

A problem in applications of ultra-high molecular weight polyethylene (UHMWPE) is the tendency for components to contain fusion defects, arising during processing of the as-polymerized powder. These defects have been implicated previously in failures of UHMWPE load-bearing surfaces, in knee and hip prostheses. Recent work of the authors has recognized two forms of defect: voids (Type 1) and particle boundaries deficient in diffusion by reptation (Type 2). To assist process and product design, a method has now been developed for predicting the decay of severity of Type 2 defects during processing, for a component of given shape and process history. A new quantifier was introduced for characterizing the progress of diffusion at Type 2 defects in UHMWPE—the maximum reptated molecular mass M ˆ . This was computed using results from reptation theory, embedded within a Finite Element thermal model of the process. The method was illustrated by simulating compression moulding trials already carried out experimentally by the same authors. It was discovered that M ˆ never reached the viscosity average molecular mass of the polymer, indicating incomplete boundary diffusion, and explaining the previous observation of Type 2 defects even in fully-compacted, apparently perfect mouldings. The method described has potential as a design tool, especially for optimizing manufacture of UHMWPE prosthesis components.

Wear and surface analysis of 38 mm ceramic-on-metal total hip replacements under standard and severe wear testing conditions

The purpose of this study was to compare the wear of zirconia-toughened alumina (ZTA) and alumina femoral heads tested against as-cast CoCrMo alloy acetabular cups under both standard and severe wear conditions. A new severe test, which included medio-lateral displacement of the head and rim impact upon relocation, was developed. This resulted in an area of metal transfer and an area of increased wear on the superior-anterior segment of the head that were thought to be due to dislocation and rim impact respectively. While the wear of all ceramic heads was immeasurable using the gravimetric method, the wear rates for the metallic cups from each test were readily calculated. An average steady state wear rate of 0.023 ± 0.005 mm3/106 cycles was found for the cups articulating against ZTA under standard wear conditions. A similar result had previously been obtained for the wear of cups articulated against alumina heads of the same size (within the same laboratory). Under severe wear conditions an increase in the metallic cup steady state wear rate was found with the ZTA and alumina tests giving 0.623 ± 0.252 and 1.35 ± 0.154 mm3/106 cycles respectively. Wear of the ceramic heads was detected using atomic force microscopy which showed, under severe wear conditions, a decrease in polishing marks and occasional grain removal. The surfaces of the ZTA heads tested under standard conditions were virtually unchanged from the unworn samples. Friction tests showed low friction factors for all components, pre and post wear.

Premature failure of Kinemax Plus total knee replacements

We describe a cohort of patients with a high rate of mid-term failure following Kinemax Plus total knee replacement inserted between 1998 and 2001. This implant has been recorded as having a survival rate of 96% at ten years. However, in our series the survival rate was 75% at nine years. This was also significantly lower than that of subsequent consecutive series of PFC Sigma knee replacements performed by the same surgeon. No differences were found in the clinical and radiological parameters between the two groups. At revision the most striking finding was polyethylene wear. An independent analysis of the polyethylene components was therefore undertaken. Scanning electron microscopy revealed type 2 fusion defects in the ultra-high molecular weight polyethylene (UHMWPE), which indicated incomplete boundary fusion. Other abnormalities consistent with weak UHMWPE particle interface strength were present in both the explanted inserts and in unused inserts from the same period. We consider that these type 2 fusion defects are the cause of the early failure of the Kinemax implants. This may represent a manufacturing defect resulting in a form of programmed polyethylene failure.

Quantitative constitutive behaviour and viscoelastic properties of fresh flexor tendons.

The objective of this study was to obtain detailed high quality experimental data under well-controlled test conditions in order to quantify tendon viscoelastic behaviour and provide an experimental basis for large deformation mathematical modelling. Eighty-six fresh chicken flexor digitorum profundus (FDP) tendons were mechanically tested using an Instron 5565 universal testing machine and a Bioplus bath containing physiological saline solution. At low strain rates (≤ 0.001s−1), no strain rate dependence was found and the value of the elastic modulus was 324±17 MPa. At medium strain rates (0.003s−1 – 0.1s−1), the elastic stiffness increased with increasing strain rate. For example, the values of the elastic modulus were 427±10, 653±21 and 837±11 MPa for strain rates of 0.006s−1, 0.012s−1 and 0.05s−1 respectively. A series of stress relaxation experiments at different levels of strain were conducted. The higher the initial stress level, the faster the stress relaxed. For all stress relaxation tests, the relationship of normalised relaxation function G(t) against log time (ln(t)) was approximately linear (R2 = 0.935 ± 0.028) and this supports Fungs quasi-linear viscoelasticity (QLV) hypothesis. Some preliminary work on bovine flexor tendons using a video extensometer is also reported.

A dimensionless ordered pull-through model of the mammalian lens epithelium evidences scaling across species and explains the age-dependent changes in cell density in the human lens

We present a mathematical (ordered pull-through; OPT) model of the cell-density profile for the mammalian lens epithelium together with new experimental data. The model is based upon dimensionless parameters, an important criterion for inter-species comparisons where lens sizes can vary greatly (e.g. bovine (approx. 18 mm); mouse (approx. 2 mm)) and confirms that mammalian lenses scale with size. The validated model includes two parameters: β/α, which is the ratio of the proliferation rate in the peripheral and in the central region of the lens; and γGZ, a dimensionless pull-through parameter that accounts for the cell transition and exit from the epithelium into the lens body. Best-fit values were determined for mouse, rat, rabbit, bovine and human lens epithelia. The OPT model accounts for the peak in cell density at the periphery of the lens epithelium, a region where cell proliferation is concentrated and reaches a maximum coincident with the germinative zone. The β/α ratio correlates with the measured FGF-2 gradient, a morphogen critical to lens cell survival, proliferation and differentiation. As proliferation declines with age, the OPT model predicted age-dependent changes in cell-density profiles, which we observed in mouse and human lenses.

Oxidation and fusion defects synergistically accelerate polyethylene failure in knee replacement

We have previously reported upon a cohort of patients with premature failure of such material and postulated upon the impact of abnormally high concentrations of type 2 fusion defects whereby there is a lack of particle cohesion due to incomplete diffusion. In vivo oxidation has been purported to underscore the premature failure of polyethylene. The mechanism of such remains poorly delineated. New data has now been obtained by determining substrata oxidative profiles of 10 failed Kinemax Plus modular tibial insert analyses in conjunction with fusion defect detection. The full thickness of a series of cores was analysed using infra-red spectroscopy to identify higher levels of oxidation in loaded used material at both the articulating and non-articulating regions. A comparison was made to an unused control. Articulating, loaded, areas exhibited greater local concentrations of oxidised material and wider variation of such consistent with the higher presence of fusion defects. Subsurface analysis confirmed the presence of a major oxidative peak 2mm below the surface for all loaded areas irrespective of wear. Additionally we were able to identify a second major oxidative focus about halfway between the inferior (tibial baseplate) surface and the articulating area. We believe that the combination of high oxidation and fusion defects represents a second high stress zone consistent with the observation of tibial baseplate polyethylene dissociation and backside wear with resultant catastrophic material failure.