Adjusting the physico-chemical properties of collagen scaffolds to accommodate primary osteoblasts and endothelial cells

Acknowledgements: This research was financially supported by the Engineering and Physical Sciences Research Council (EPSRC) and Geistlich Pharma AG. R.E.C. and S.M.B. acknowledge funding from an EPSRC Professorial Fellowship (EP/N019938/1), which also supported the research undertaken by D.V.B. D.V.B. would like to thank the Cambridge Royce facilities grant EP/P024947/1 and Sir Henry Royce Institute—recurrent grant EP/R00661X/1.Collagen-based biomaterials are used widely as tissue engineering scaffolds because of their excellent bioactivity and their similarity to the natural ECM. The regeneration of healthy bone tissue requires simultaneous support for both osteoblasts and, where angiogenesis is intended, endothelial cells. Hence it is important to tailor carefully the biochemical and structural characteristics of the scaffold to suit the needs of each cell type. This work describes for the first time a systematic study to gain insight into the cell type-specific response of primary human osteoblast (hOBs) and human dermal microvascular endothelial cells (HDMECs) to insoluble collagen-based biomaterials. The behaviour was evaluated on both 2D films and 3D scaffolds, produced using freeze-drying. The collagen was cross-linked at various EDC/NHS concentrations and mono-cultured with hOBs and HDMECs to assess the effect of architectural features and scaffold stabilization on cell behaviour. It was observed that 3D scaffolds cross-linked at 30% of the standard conditions in literature offered an optimal combination of mechanical stiffness and cellular response for both cell types, although endothelial cells were more sensitive to the degree of cross-linking than hOBs. Architectural features have a time-dependent impact on the cell migration profile, with alignment being the most influential parameter overall