Bioresorbable microspheres by spinning disk atomization as injectable cellcarrier: from preparation to in vitro evaluation

Vesico-ureteral reflux, a common pathology in children, can be treated cyst oscopically by injection of a bulking material underneath the most distal, intramural ureter, which forces the latter to do a detour, increasing its s ubmucosal path. This increase of the length of the submucosal path of the u reter within the bladder is directly responsible for the anti-reflux effect . So far Teflon and collagen paste have been commonly used as bulking mater ials. We suggest replacing these materials by living tissue consisting of b ladder smooth muscle, normally present at this location. The aim of this wo rk 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 t he 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(lacti c acid) microspheres with tunable sizes from 160 to 320 mu m. The controlle d solvent burst method has shown the advantage over the crystal leaching me thod in the direct creation of microspheres with large closed pores, by ato mizing the polymer solution in controlled temperature conditions. Microsphe res with various closed pore structures have thus been prepared. The innova tion of this work is in the direct and rapid formation of porous microspher es with a pore morphology which is designed to create cavities suitable for adherence and growth of cells by adapting the temperature conditions of at omization. Injection tests have shown promising results in using these cell -loaded microspheres for future non-invasive tissue engineering. (C) 2000 E lsevier Science Ltd. All rights reserved.