Abstract

Tissue engineering scaffolds are used in conjunction with stem cells for the treatment of various diseases. A number of factors provided by the scaffolds affect the differentiation of stem cells. Mechanical cues that are part of the natural cellular microenvironment can both accelerate the differentiation toward particular cell lineages or induce differentiation to an alternative cell fate. Among such factors, there are externally applied strains and mechanical (stiffness and relaxation time) properties of the extracellular matrix. Here, the mechanics of a fibrous-porous scaffold is studied by applying a coordinated modeling and experimental approach. A force relaxation experiment is used, and a poroelastic model associates the relaxation process with the fluid diffusion through the fibrous matrix. The model parameters, including the stiffness moduli in the directions along and across the fibers as well as fluid diffusion time, are estimated by fitting the experimental data. The time course of the applied force is then predicted for different rates of loading and scaffold porosities. The proposed approach can help in a reduction of the technological and experimental efforts to produce 3-D scaffolds for regenerative medicine as well as in a higher accuracy of the estimation of the local factors sensed by stem cells.

Highlights

  • Scaffolds, a key part of regenerative medicine, control the microenvironment for adhesion, migration, proliferation, and differentiation of cells inside[1]

  • The quality of the model is subjected to an additional test where the parameters estimated from the experiment corresponding to one strain rate are used for the prediction of the relaxation process corresponding to a different rate and the predicted modeling results are compared with the experiment with the same rate

  • We have shown here that the relaxation properties of such scaffolds can be explained by the fluid diffusion after the loading of the sample, and we have extended the analyses of short cylinders under compression to those of long cylinders under tension

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Summary

Introduction

A key part of regenerative medicine, control the microenvironment for adhesion, migration, proliferation, and differentiation of cells inside[1] (for review). Fibrous-porous scaffolds mimicking the natural structure of tissue are effectively used in applications like skeletal muscle and tendon. Stiffness of the extracellular matrix (ECM) directs stem cell differentiation toward neurogenesis, myogenesis, and osteogenesis, within ranges of 0.1–1 kPa, 8–17 kPa, are 25–40 kPa typical to brain, muscle, and bone tissues, respectively[13,14]. The viscoelastic properties of ECM, stress relaxation time[15,16] and loss modulus[17,18], affect stem cell differentiation (osteogenesis). After the estimation of the scaffold material parameters, the local stresses, strains, and velocities sensed by stem cells can be obtained as functions of time for different porosities and strain rates, resulting in a more accurate prediction of stem cell differentiation

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