In the design of macroporous biomaterial scaffolds, attention is payed predominantly to the readily accessible macroscopic mechanical properties rather than to the mechanical properties experienced by the cells adhering to the material. However, the direct cell mechanical environment has been shown to be of special relevance for biological processes such as proliferation, differentiation and extracellular matrix formation both in vitro and in vivo. In this study we investigated how individual architectural features of highly aligned macroporous collagen scaffolds contribute to its mechanical properties on the macroscopic vs. the microscopic scale. Scaffolds were produced by controlled freezing and freeze-drying, a method frequently used for manufacturing of macroporous biomaterials. The individual architectural features of the biomaterial were carefully characterized to develop a finite element model (FE-model) that finally provided insights in the relation between the biomaterial's mechanical properties on the macro-scale and the properties on the micro-scale, as experienced by adhering cells. FE-models were validated by experimental characterization of the scaffolds, both on the macroscopic and the microscopic level, using mechanical compression testing and atomic force microscopy. As a result, a so-called cell-effective stiffness of these non-trivial scaffold architectures could be predicted for the first time. A linear dependency between the macroscopic scaffold stiffness and the cell-effective stiffness was found, with the latter being consistently higher by a factor of 6.4 ± 0.6. The relevance of the cell-effective stiffness in controlling progenitor cell differentiation was confirmed in vitro. The obtained information about the cell-effective stiffness is of particular relevance for the early stages of tissue regeneration, when the cells first populate and interact with the biomaterial. Beyond the specific biomaterial investigated here, the introduced method is transferable to other complex biomaterial architectures. Design-optimization in 3D macroporous scaffolds that are based on a deeper understanding of the mechanical environment provided to the cells will help to enhance biomaterial-based tissue regeneration approaches.

Small calibre vascular prostheses (<6 mm) still lack medium and long term patency. Inelasticity of the prosthesis is one of the characteristics, which is involved in the mechanisms of failure (e.g. the development of neointimal hyperplasia at the distal anastomosis). Here we report about covalently crosslinked poly(n-butyl acrylate) networks (cPnBA) with adjustable elastic moduli, which can be tailored to values of human arteries (between 100 and 1000 kPa). Motivated by the potential application of such polymer networks as cardiovascular prosthesis, adhesion, activation and thrombus formation of human platelets on cPnBA networks were evaluated. All cPnBA-samples displayed a high thrombogenicity compared to the control (silicone). Significantly less platelets adhered on the surface of the soft cPnBA04 than on cPnBA73. All cPnBA samples displayed a higher number of platelet aggregates and a lower number of inactivated platelets in comparison to the control. While the elastic modulus of cPnBA networks could be successfully adjusted to that of human arteries, the tested polymers did not show an optimal hemocompatibility. Future studies aim at improving the biofunctionality by surface modification of these polymer networks.