Bioresorbable microspheres by spinning disk atomization as injectable cell carrier: from preparation to in vitro evaluation.

Vesico-ureteral reflux, a common pathology in children, can be treated cystoscopically by injection of a bulking material underneath the most distal, intramural ureter, which forces the latter to do a detour, increasing its submucosal path. This increase of the length of the submucosal path of the ureter within the bladder is directly responsible for the anti-reflux effect. So far Teflon and collagen paste have been commonly used as bulking materials. We suggest replacing these materials by living tissue consisting of bladder smooth muscle, normally present at this location. The aim of this work is to provide a long-term effective treatment by producing bioresorbable microspheres which can act as a support matrix and an entrapment substance for bladder smooth muscle cells, with the goal of an in vivo transfer of the in vitro cultured cells with a minimal surgical procedure. By the use of Spinning Disk Atomization, which has specifically been developed for this purpose, we have shown two methods for the preparation of porous poly(lactic acid) microspheres with tunable sizes from 160 to 320 microm. The controlled solvent burst method has shown the advantage over the crystal leaching method in the direct creation of microspheres with large closed pores, by atomizing the polymer solution in controlled temperature conditions. Microspheres with various closed pore structures have thus been prepared. The innovation of this work is in the direct and rapid formation of porous microspheres with a pore morphology which is designed to create cavities suitable for adherence and growth of cells by adapting the temperature conditions of atomization. Injection tests have shown promising results in using these cell-loaded microspheres for future non-invasive tissue engineering.

Alginate hydrogel microspheres and microcapsules prepared by spinning disk atomization.

Our spinning disk atomization (SDA) can, relative to other existing techniques, produce micron-sized particles with very narrow size distribution. The aim of this work is to present this technology for the production of alginate microspheres and microcapsules. We atomized and gelled aqueous alginate solutions into very narrowly dispersed microspheres with sizes ranging from 300 to 600 microm. Here, the interest is to produce, at high rate, particles of a given size with a narrow size distribution and also to show a new method of encapsulation using SDA. The viscosity and flow rate contributions in the drop formation is qualitatively analyzed to show how they affect droplet size. In addition, a technique for high degree of encapsulation is presented in which yeast is used as a model system. The production of yeast-loaded microspheres by SDA shows the potential of the technique for biotechnology applications.

Synthesis, structure and surface dynamics of phosphorycholine functional biomimicking polymers.

2-Acryloyloxyethyl phosphorylcholine (APC) was synthesised and copolymerised with methyl methacrylate (MMA) and methyl acrylate (MA) to lead to a PC functional terpolymer. Bulk and solution properties were assessed through elemental analysis, DSC and 1H-NMR. The possibility of chain transfer was discussed. Surface properties were investigated by ToF-SIMS and XPS as well as in vitro assays to assess the non-fouling characteristic of the terpolymer. It was found that a low PC concentration generates an amphiphile terpolymer and is responsible for the organisation of the bulk into a microphase separated morphology with enriched PC domains dispersed in a (MMA-MA) matrix. The presence of PC micelles in non-polar solvent could also be deduced from the analysis of the polymer structure behaviour in solution. Finally, surface reorganisation of the terpolymer was shown to be highly dependent upon the affinities of the PC group for its environment and owing to surface compliance, a low PC content was already sufficient to strongly reduce cell attachment.