Skip to main content

An integrated multidisciplinary tissue engineering approach combining novel high-throughput screening and advanced methodologies to create complex biomaterials-stem cells constructs

Final Report Summary - COMPLEXITE (An integrated multidisciplinary tissue engineering approach combining novel high-throughput screening and advanced methodologies to create complex biomaterials-stem cells constructs)

ComplexiTE ultimate goal is to define a multi-parametric methodology that allows the screening of combinations of biomaterials, cells and culture conditions in order to define the ideal ones to obtain a bona fide bone tissue-like structure. In fact, one tissue formation requires an orchestrated interaction between several cell types such as osteoblasts and endothelial cells. The developed platforms can then be used for several other tissues and scientific approaches. ComplexiTE has been taking advantage of adipose tissue as a source of mesenchymal stem cells with high differentiation and proliferation capacity, as well as of specific sub-populations with enhanced differentiation potential into the osteogenic and endothelial lineages. Our findings demonstrate the possibility of using a subpopulation of adipose tissue as a single cell source to create 3D bone tissue-like models, which is a clear step forward in the regeneration of vascularized bone tissue. Moreover, the intrinsic vascularization/angiogenic potential of SVF cells has been originally explored, by means of setting up quite specific culture conditions in the absence of extrinsic growth factors.
An original library of marine origin materials was defined and tested to create 3D hydrogel microenvironments. Other materials were either combined with the distinct marine origin materials or used as a common base matrix for the production of 3D hydrogels containing the different marine-origin materials. A major innovation of ComplexiTE project is the unique microfluidic apparatus designed for the production of the 3D hydrogels. Different approaches were followed which confers a high versatility to the novel method. It exploits the low mixing properties of laminar flow (typical of microfluidic systems) to create (k)meter-long (if necessary) fibres containing separate cell-laden compartments. The composition of the compartments can be controlled, obtaining a linear variation of composition along the fibre. Furthermore, the composition of the compartments can be evaluated without using destructive techniques, thus allowing for unique high-throughput analysis of the cell-material interactions.
The described achievements in terms of cell sources, materials and microfluidic system, allowed for the successful generation of 3D cell-laden hydrogel arrays. The most promising conditions were scaled up and used to produce 3D structures by 3D printing techniques to confirm that the developed platform can be used as a high-throughput system from which the best material and (co)-culture conditions for a successful bone tissue engineering strategy can be extrapolated.