Improving 3D matrices for tissue engineering using advanced drug delivery techniques

Wang, Yiwei (2007) Improving 3D matrices for tissue engineering using advanced drug delivery techniques. (PhD thesis), Kingston University, .


Micro/macroporous matrices comprising a continuous phase of poly([epsilon]-caprolactone) . (PCL) and a dispersed phase of water soluble particles (lactose and gelatin) with defined size range (45-90, 90-125 and l25-250[mu]m) were produced by rapid cooling solutions of PCL in acetone followed by solvent extraction from the hardened material. This novel approach enables high loading (29-44% w/w) of particles (lactose and gelatin) to be achieved in PCL matrices by suspension of particulates in the PCL solution prior to casting. Highly efficient protein release (90%) was obtained over time periods of 3 days to 3 weeks by variation of particle loading and particle size range. The good particle distribution throughout the matrix and efficient extraction of the water-soluble phase allows formation of a macroporous structure with defined pore architecture by incorporation of particles of a specific shape and size range. SEM analysis revealed the porous surface morphology. Micro computed tomography (micro-CT) and image analysis enabled visualization of the internal 3-D pore structure, quantification of the frequency distribution of equivalent pore diameter and porosity (%) in peL matrices. Micro/macroporous PCL tubes exhibited a burst strength of 125 to l45MPa under hydrostatic loading at 37[degree]C and good recovery of tube diameter following short-duration flow rates of 1000 ml/min under continuous increasing and pulsatile conditions. Sustained release of incorporated enzymes (lysozyme, collagenase and catalase) occurred over 11 days from the PCL matrices, with retained activity dependent on the particular enzyme used (collagenase 100% at 11 days, lysozyme 75-80% at 11 days, catalase 10-20 % at 5 days). Swiss3T3 fibroblasts exhibited strong attachment and successful colonization of the surface. of PCL matrices over 8 to 15 days in cell culture. These findings demonstrate the potential of micro/macroporous PCL matrices for scaffold production in tissue engineering and for controlling drug delivery.

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