Advanced Organotypic Membrane Systems and Mesenchymal Stem Cells in Skin and Liver Tissue Engineeering

Advanced organotypic tissues made of polymeric membranes and human cells, in both homotypic and heterotypic co-culture systems with mesenchymal stem cells (MSCs), were developed as an ambitious attempt for the bio-fabrication of self-renewing human tissue models. Polymeric membranes mimic the in-vivo 3D microenvironment, recapitulating the natural niches for hosting cells and promoting cell-cell and cell-matrix interactions. Through the modulation of the preparation process parameters, membranes with specific functionalities and structural features can be designed, representing a challenging strategy for the control of the cellular fate. Specific membranes properties provide the biochemical stimuli and mechanical support able to boost cellular adhesion, proliferation and differentiation, and thus the overall morpho-functional behaviour [1-3]. Porous semipermeable membranes enable the compartmentalization and the physical separation of cells allowing in the meantime their crosstalk by the selective mass transfer of the secreted paracrine factors, and therefore mimicking the in-vivo physiological cell niches [4-5]. Moreover, the membrane loading with a bioactive molecule constantly released in the time, represents a further strategy to trigger or modulate biological processes needed for tissue regeneration and repair. Innovative culture strategies, by using engineered membrane biohybrid systems for cell compartmentalization and colonization will be presented in this work. Engineered microenvironments made by the combination of biodegradable membranes with human skin cells were created as skin models. Organotypic membrane bioreactors utilizing primary human hepatocytes in direct and connected co-culture systems with human endothelial and MSCs offered interesting opportunities for the design of bioartificial livers as in-vitro models with high morpho-functional performance.