Mechanisms of structure generation during plastic compression of nanofibrillar collagen hydrogel scaffolds: towards engineering of collagen.

Operator control of cell/matrix density of plastically compressed collagen hydrogel scaffolds critically depends on reproducibly limiting the extent of scaffold compaction, as fluid expulsion. A functional model of the compression process is presented, based on the idea that the main fluid-leaving surface (FLS) behaves as an ultrafiltration membrane, allowing fluid (water) out but retaining collagen fibrils to form a cake. We hypothesize that accumulation of collagen at the FLS produces anisotropic structuring but also increases FLS hydraulic resistance (R-FLS), in turn limiting the flux. Our findings show that while compressive load is the primary determinant of flux at the beginning of compression (load-dependent phase), increasing FLS collagen density (measured by X-ray attenuation) and increasing R-FLS become the key determinants of flux as the process proceeds (flow-dependent phase). The model integrates these two phases and can closely predict fluid loss over time for a range of compressive loads. This model provides a useful tool for engineering cell and matrix density to tissue-specific levels, as well as generating localized 3D nano micro-scale structures and zonal heterogeneity within scaffolds. Such structure generation is important for complex tissue engineering and forms the basis for process automation and up-scaling. Copyright (C) 2010 John Wiley & Sons, Ltd.