A p-type finite element solution for the simulation of O2 transport in articular cartilage tissue: heterogeneous and porous media.

The partial pressure of oxygen (pO2) is suggested to have a regulatory effect on chondrocyte biosynthetic activities, and its effect during expansion is unknown. The authors hypothesize that oxygen tension due to mechanical deformation or swelling could be as important as direct mechanical effects on cell biosynthetic activities. While there are plenty of studies on measuring and/or modelling pO2 in articular cartilage (AC) for static (rest) conditions, to the best of the authors' knowledge there are very few such studies on pO2 in AC for dynamic conditions such as swelling or tissue deformation. In this study, it is attempted to develop a model to study the dynamics of oxygen transport in AC. A high-precision hybrid element is designed using the p-type finite element method, by which diffusion and convection are incorporated as a single element. A domain decomposition method is used that allows the use of a different type of discretization with independent discretization variables in non-overlapping sub-domains, for a generic three-dimensional approach to elliptic boundary value problems of order 2 or higher. The formulation developed in this study might be used in determining the necessary flow conditions to cultivate tissue constructs in tissue repair and tissue engineering.

Conjugation of fibronectin onto three-dimensional porous scaffolds for vascular tissue engineering applications.

Tissue engineering scaffolds provide the three-dimensional (3-D) geometry and mechanical framework required for regulating cell behavior and facilitating tissue maturation. Unfortunately, most synthetic scaffolds lack the biological recognition motifs required for seeded cell interaction. In order to impart this recognition, synthetic scaffolds should possess appropriate biological functionality. Here, for the first time, we present a comprehensive study of fibronectin (FN) conjugation onto highly porous 3-D poly(carbonate) urethane scaffolds through grafted poly(acrylic acid) spacers on the urethane backbone. Scanning electron microscopy was used to ensure that the porous structures of the scaffolds were preserved throughout the multiple conjugation steps, and Fourier transform infrared spectroscopy was used to monitor the reaction progress. Toluidine blue staining revealed that increasing acrylic acid concentration and grafting time increased the number of poly(acrylic acid) groups incorporated. High resolution X-ray photoelectron spectroscopy studies of the scaffolds demonstrated an increase in nitrogen and sulfur due to FN conjugation. Immunofluorescence microscopy studies showed an even distribution of conjugated FN on the 3-D scaffolds. Cell culture studies using human coronary artery smooth muscle cells demonstrated that FN-conjugated scaffolds had improved cell attachment and infiltration depth compared with scaffolds without FN conjugation and with those scaffolds on which FN was merely adsorbed.

A Galerkin-type finite element solution for simulation of mass diffusion in the application of tissue engineering: heterogeneous and non-porous media.

This study is an effort to produce a generic and comprehensive solution to the simulation of mass diffusion through a multiphasic and heterogeneous material model. A Galerkin-type finite element formulation is developed to solve Fick's equation for steady-state and time-dependent analysis. The effect of the interface in modelling of a liquid-solid medium is presented in this work. To show the robustness of the proposed approach, the gas exchange (oxygen and carbon dioxide) process through the capillary network between the alveolar membrane and red blood cells has been analysed and then validated with experimental data. The current work is a significant asset to modelling the diffusion of oxygen between cells and scaffolds in tissue engineering or tissue regeneration/repair studies. It is one step towards the development of high-order elements for application of the simulation of mass transfer through a multiphasic and porous model with varying degrees of interconnectivity and pore size for tissue engineering applications.

Modification, crosslinking and reactive electrospinning of a thermoplastic medical polyurethane for vascular graft applications.

Thermoplastic polyurethanes are used in a variety of medical devices and experimental tissue engineering scaffolds. Despite advances in polymer composition to improve their stability, the correct balance between chemical and mechanical properties is not always achieved. A model compound (MC) simulating the structure of a widely used medical polyurethane (Pellethane) was synthesized and reacted with aliphatic and olefinic acyl chlorides to study the reaction site and conditions. After adopting the conditions to the olefinic modification of Pellethane, processing into flat sheets, and crosslinking by thermal initiation or ultraviolet radiation, mechanical properties were determined. The modified polyurethane was additionally electrospun under ultraviolet light to produce a crosslinked tubular vascular graft prototype. Model compound studies showed reaction at the carbamide nitrogen, and the modification of Pellethane with pentenoyl chloride could be accurately controlled to up to 20% (correlation: rho=0.99). Successful crosslinking was confirmed by insolubility of the materials. Initiator concentrations were optimized and the crosslink densities shown to increase with increasing modification. Crosslinking of Pellethane containing an increasing number of pentenoyl groups resulted in decreases (up to 42%, p<0.01) in the hysteresis and 44% in creep (p<0.05), and in a significant improvement in degradation resistance in vitro. Modified Pellethane was successfully electrospun into tubular grafts and crosslinked using UV irradiation during and after spinning to render them insoluble. Prototype grafts had sufficient burst pressure (>550 mm Hg), and compliances of 12.1+/-0.8 and 6.2+/-0.3%/100 mm Hg for uncrosslinked and crosslinked samples, respectively. It is concluded that the viscoelastic properties of a standard thermoplastic polyurethane can be improved by modification and subsequent crosslinking, and that the modified material may be electrospun and initiated to yield crosslinked scaffolds. Such materials hold promise for the production of vascular and other porous scaffolds, where decreased hysteresis and creep may be required to prevent aneurismal dilation.

2-methacryloyloxyethyl N-butylcarbamate: a new co-monomer for synthesis of polyurethane hydrogels with improved mechanical properties for biomedical applications.

Hydrogels with tunable hydrophilic and mechanical properties were synthesized by the free radical polymerization of 2-hydroxyethyl methacrylate (HEMA) and 2-methacryloyloxyethyl N-butylcarbamate. The resulting hydrogels were investigated for their equilibrium water content, sessile drop water contact angles, gel fraction, mechanical properties and protein adsorption. Results indicated that co-polymer hydrogels have good hydrophilicity and that, with the incorporation of the 2-methacryloyloxyethyl N-butylcarbamate, mechanical properties could be improved significantly. without affecting other important properties. Lysozyme and albumin adsorption experiments demonstrated that, similar to most hydrogel materials, the co-polymer hydrogels adsorb more lysozyme than albumin and that the adsorption was dependent on hydrophilicity. The control poly(HEMA) hydrogels were found to adsorb more protein than the co-polymer hydrogels; this is thought to be primarily a consequence of protein absorption rather than protein adsorption.