Transport analysis of bioreactors for the in vitro culture of ovarian tissue

Many papers have recently reported on the in vitro culture of ovarian tissue or isolated follicles. Strips of ovarian tissue have been cultured to understand the mechanisms and the hormonal requirements of the activation of primordial follicles, their growth, and development of steroidogenic capacities. Isolated follicles, encapsulated in hydrogel matrices, have been cultured to study how to promote follicle development in vitro and how to exploit the reproductive potential of cryopreserved ovarian tissue of pre-pubertal girls with premature ovarian failure or of women needing immediate cancer treatment. Culture techniques have also been proposed as in vitro models to study folliculogenesis, to screen new drugs, and for toxicological studies. Ma ny publications address the optimization of culture media and supplements provision, and of the matrices used for encapsulating ovarian tissue and follicles. Bioreactors have been proposed which are suited to the small scale of the tissue samples, varying for configuration and operation mode with the aim of enhancing and controlling transport of nutrients, oxygen and biochemical cues to tissue. The broadly differing bioreactor types and operating conditions that have been proposed suggest that the optimization of bioreactor design is often approached in empiric fashion without paying due attention to the interplay of occurring flow and mass transport phenomena and cells metabolism. In this paper, the theoretical aspects of solutes transport to cells in ovarian tissue or encapsulated follicle preparations are briefly discussed, and used for analyzing the relevant transport features of some bioreactors proposed for ovarian tissue culture. The analysis suggests that a rational and multidisciplinary approach to bioreactor design for ovarian tissue and follicle culture in vitro is highly desirable to exploit the full potential of in vitro culture techniques and to advance knowledge in the field of assisted reproduction.