Dynamics of in vitro polymer degradation of polycaprolactone-based scaffolds : accelerated versus simulated physiological conditions

The increasing use of biodegradable devices in tissue engineering and regenerative medicine means it is essential to study and understand their degradation behaviour. Accelerated degradation systems aim to achieve similar degradation profiles within a shorter period of time, compared with standard conditions. However, these conditions only partially mimic the actual situation, and subsequent analyses and derived mechanisms must be treated with caution and should always be supported by actual long-term degradation data obtained under physiological conditions. Our studies revealed that polycaprolactone (PCL) and PCL-composite scaffolds degrade very differently under these different degradation conditions, whilst still undergoing hydrolysis. Molecular weight and mass loss results differ due to the different degradation pathways followed (surface degradation pathway for accelerated conditions and bulk degradation pathway for simulated physiological conditions). Crystallinity studies revealed similar patterns of recrystallization dynamics, and mechanical data indicated that the scaffolds retained their functional stability, in both instances, over the course of degradation. Ultimately, polymer degradation was shown to be chiefly governed by molecular weight, crystallinity susceptibility to hydrolysis and device architecture considerations whilst maintaining its thermodynamic equilibrium.

Behaviour of image degradation model in multiresolution

Multiresolution techniques are being extensively used in signal processing literature. This paper has two parts, in the first part we derive a relationship between the general degradation model (Y=BX+W) at coarse and fine resolutions. In the second part we develop a signal restoration scheme in a multiresolution framework and demonstrate through experiments that the knowledge of the relationship between the degradation model at different resolutions helps in obtaining computationally efficient restoration scheme.

An integrated rail track degradation model

There has been a worldwide trend to increase axle loads and train speeds. This means that railway track degradation will be accelerated, and track maintenance costs will be increased significantly. There is a need to investigate the consequences of increasing traffic load. The aim of the research is to develop a model for the analysis of physical degradation of railway tracks in response to changes in traffic parameters, especially increased axle loads and train speeds. This research has developed an integrated track degradation model (ITDM) by integrating several models into a comprehensive framework. Mechanistic relationships for track degradation hav~ ?een used wherever possible in each of the models contained in ITDM. This overcc:mes the deficiency of the traditional statistical track models which rely heavily on historical degradation data, which is generally not available in many railway systems. In addition statistical models lack the flexibility of incorporating future changes in traffic patterns or maintenance practices. The research starts with reviewing railway track related studies both in Australia and overseas to develop a comprehensive understanding of track performance under various traffic conditions. Existing railway related models are then examined for their suitability for track degradation analysis for Australian situations. The ITDM model is subsequently developed by modifying suitable existing models, and developing new models where necessary. The ITDM model contains four interrelated submodels for rails, sleepers, ballast and subgrade, and track modulus. The rail submodel is for rail wear analysis and is developed from a theoretical concept. The sleeper submodel is for timber sleepers damage prediction. The submodel is developed by modifying and extending an existing model developed elsewhere. The submodel has also incorporated an analysis for the likelihood of concrete sleeper cracking. The ballast and subgrade submodel is evolved from a concept developed in the USA. Substantial modifications and improvements have been made. The track modulus submodel is developed from a conceptual method. Corrections for more global track conditions have been made. The integration of these submodels into one comprehensive package has enabled the interaction between individual track components to be taken into account. This is done by calculating wheel load distribution with time and updating track conditions periodically in the process of track degradation simulation. A Windows-based computer program ~ssociated with ITDM has also been developed. The program enables the user to carry out analysis of degradation of individual track components and to investigate the inter relationships between these track components and their deterioration. The successful implementation of this research has provided essential information for prediction of increased maintenance as a consequence of railway trackdegradation. The model, having been presented at various conferences and seminars, has attracted wide interest. It is anticipated that the model will be put into practical use among Australian railways, enabling track maintenance planning to be optimized and potentially saving Australian railway systems millions of dollars in operating costs.

The p38 mitogen-activated protein kinase regulates interleukin-1beta-induced IL-8 expression via an effect on the IL-8 promoter in intestinal epithelial cells

Several lines of evidence implicate the p38 mitogen-activated protein kinase (p38 MAPK) in the proinflammatory response to bacterial agents and cytokines. Equally, the transcription factor, nuclear factor (NF)-kappaB, is recognized to be a critical determinant of the inflammatory response in intestinal epithelial cells (IECs). However, the precise inter-relationship between the activation of p38 MAPK and activation of the transcription factor NF-kappaB in the intestinal epithelial cell (IEC) system, remains unknown. Here we show that interleukin (IL)-1beta activates all three MAPKs in Caco-2 cells. The production of IL-8 and monocyte chemotactic protein 1 (MCP-1) was attenuated by 50% when these cells were preincubated with the p38 MAPK inhibitor, SB 203580. Further investigation of the NF-kappaB signalling system revealed that the inhibitory effect was independent of the phosphorylation and degradation of IkappaBalpha, the binding partner of NF-kappaB. This effect was also independent of the DNA binding of the p65 Rel A subunit, as well as transactivation, determined by an NF-kappaB luciferase construct, using both SB 203580 and dominant-negative p38 MAPK. Evaluation of IL-8 and MCP-1 RNA messages by reverse transcription-polymerase chain reaction (RT-PCR) revealed that the inhibitory effect of SB 203580 was associated with a reduction in this parameter. Using an IL-8-luciferase promoter construct, an effect of p38 upon its activation by both pharmacological and dominant-negative p38 construct co-transfection was demonstrated. It is concluded that p38 MAPK influences the expression of chemokines in intestinal epithelial cells, through an effect upon the activation of the chemokine promoter, and does not directly involve the activation of the transcription factor NF-kappaB

Photo-cross-linked poly(D,L-lactide)-based networks. Structural characterization by HR-MAS NMR spectroscopy and hydrolytic degradation behavior

To date, biodegradable networks and particularly their kinetic chain lengths have been characterized by analysis of their degradation products in solution. We characterize the network itself by NMR analysis in the solvent-swollen state under magic angle spinning conditions. The networks were prepared by photoinitiated cross-linking of poly(dl-lactide)−dimethacrylate macromers (5 kg/mol) in the presence of an unreactive diluent. Using diffusion filtering and 2D correlation spectroscopy techniques, all network components are identified. By quantification of network-bound photoinitiator fragments, an average kinetic chain length of 9 ± 2 methacrylate units is determined. The PDLLA macromer solution was also used with a dye to prepare computer-designed structures by stereolithography. For these networks structures, the average kinetic chain length is 24 ± 4 methacrylate units. In all cases the calculated molecular weights of the polymethacrylate chains after degradation are maximally 8.8 kg/mol, which is far below the threshold for renal clearance. Upon incubation in phosphate buffered saline at 37 °C, the networks show a similar mass loss profile in time as linear high-molecular-weight PDLLA (HMW PDLLA). The mechanical properties are preserved longer for the PDLLA networks than for HMW PDLLA. The initial tensile strength of 47 ± 2 MPa does not decrease significantly for the first 15 weeks, while HMW PDLLA lost 85 ± 5% of its strength within 5 weeks. The physical properties, kinetic chain length, and degradation profile of these photo-cross-linked PDLLA networks make them most suited materials for orthopedic applications and use in (bone) tissue engineering.