Biohybrid Membrane Systems and Mesenchymal Stem Cells in Skin and Liver Tissue Engineering

Engineered microenvironments made by the combination of porous membranes with stem cells were created as skin and liver in vitro models. Bioengineered skin substitutes were realized by combining biodegradable membranes and MSCs isolated from human dermis, the human Skin derived Stem Cells, in homotipic and co-culture systems with keratinocytes, for the creation of dermal and dermal/epidermal constructs. 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.

Advanced biohybrid constructs made of polymeric membranes and human mesenchymal stem cells, in both homotypic and heterotypic co-culture systems with primary cells, will be presented in this work as an ambitious attempt for the creation of self-renewing human tissue models. Polymeric micro and nanostructured membranes provide the mechanical support and the biochemical stimuli able to modulate cellular responses affecting cell adhesion, proliferation and differentiation. Suitable topographical, physico-chemical and mechanical membrane properties are critical for directing stem cell fate by transmitting specific signals. Furthermore, engineered membrane bioreactors compartmentalize cells favouring the physical separation of MSCs from the primary cells by means of porous semipermeable membranes that ensures in the meantime the selective mass transfer of the secreted paracrine factors, and thus mimicking the in vivo physiological stem cell niches.