A combined unit cell and mixture theory model to investigate cell microenvironment in three-dimensional fibrillar extracellular matrix during dynamic loading
The extracellular matrix (ECM) has been shown to play an important role in determining cell fate. Towards the design of vocal fold tissue replacement and therapy, there is a need for computational model to systematize the signals as seen by the cells. In this study, a combined three-dimensional unit cell model and mixture theory was developed and used to explore the different loading signals in the cellular scale and relate it to cell inflammation during an in vitro dynamic loading experiment. The geometry of the unit cell model presented in this study was calibrated to match uniaxial loading data. Collagen fibril modulus estimated using the model was comparable to literature. The calibrated model was able to predict the stress-stretch response of the same material under equi-biaxial loading. Mixture theory was used to estimate interstitial fluid flow within the ECM. It was shown that static loading of fibroblasts cultured in 3-D collagen ECM, simulating vocal fold posturing, induced a significant cell inflammation. Interestingly, the effect of dynamic loading (in addition to the static loading) to cell inflammation was dependent on the frequency. The model showed that increasing frequency from 10Hz to 50Hz increased shear stress on fibroblast surface and fluid pressure fivefold. A combination of the increase in fluid-induced stresses and loading frequency is likely to have driven the altered PGE2 synthesis. The study demonstrated a procedure to correlate the estimation of cell micro-environment from computational modeling and in vitro dynamic loading experiment. Therefore, it presents a foundation for future use of the coupling of experimental and computational model as an important design tool to engineer the optimum microstructure for vocal fold tissue replacement. ^
Eric Nauman, Purdue University, Klod Kokini, Purdue University.
Engineering, Mechanical|Biophysics, Biomechanics