One of the main challenges in tissue engineering (TE) is to obtain optimized products, combining biomaterials, cells and soluble factors able to stimulate tissue regeneration. Multiple combinations may be considered by changing the conditions among these three factors. The unpredictable response of each combination requires time-consuming tests. High-throughput methodologies have been proposed to master such complex analysis in TE. Usually, these tests are performed using cells cultured into two-dimensional biomaterials or by dispensing arrays of cell loaded hydrogels. We propose for the first time the on-chip combinatorial study of 3D miniaturized porous scaffolds using a patterned bioinspired superhydrophobic platform. Arrays of biomaterials are dispensed and processed in situ as porous scaffolds with distinct composition, surface characteristics, porosity/pore size and mechanical properties. On-chip porosity, pore size and mechanical properties of scaffolds based on chitosan and alginate are assessed by adapting microcomputed tomography equipment and a dynamic mechanical analyzer - and cell response after 24 hours. The interactions between cell types of two distinct origins – osteoblast-like and fibroblasts - and the scaffolds modified with Fn are studied by image-based methods and validated by comparison with conventional destructive methods (dsDNA quantification and MTS tests). Physical and biological on-chip analyses are coherent with the conventional measures, and conclusions about the most favorable conditions for each cell type are taken.

We believe this type of chips will have a wide range of applications in distinct areas such as cell-materials interactions studies, tracking of nanoparticles internalization for cell differentiation or gene therapy and high-throughput analysis of the effect of different types of irradiation and drugs in tumor cell death.