Quantification of cell contractile behavior based on non-destructive macroscopic measurement of tension forces on bioprinted hydrogel

Abstract: Contraction assay based on surface measurement have been widely used to evaluate cell contractility in 3D models. This method is straightforward and requires no specific equipment, but it does not provide quantitative data about contraction forces generated by cells. We expanded this method with a new biomechanical model, based on the work-energy theorem, to provide non-destructive longitudinal monitoring of contraction forces generated by cells in 3D.We applied this method on hydrogels seeded with either fibroblasts or osteoblasts. Hydrogel mechanical characteristics were modulated to enhance (condition HCA${High}$: hydrogel contraction assay high contraction) or limit (condition HCA${Low}$: hydrogel contraction assay low contraction) cell contractile behaviors. Macroscopic measures were further correlated with cell contractile behavior and descriptive analysis of their physiology in response to different mechanical environments. Fibroblasts and osteoblasts contracted their matrix up to 47% and 77% respectively. Contraction stress peaked at day 5 with 1.1 10$^{-14}$Pa for fibroblasts and 3.5 10$^{-14}$Pa for osteoblasts, which correlated with cell attachment and spreading. Negligible contraction was seen in HCA${Low}$. Both fibroblasts and osteoblasts expressed $\alpha$-SMA contractile fibers in HCA${High}$ and HCA${Low}$. Failure to contract HCA${Low}$ was attributed to increased cross-linking and resistance to proteolytic degradation of the hydrogel.