INTRODUCTION: Mesenchymal tissue is capable of differentiating into a variety of soft skeletal tissues. It is known that mechanical stresses play a role in this process, however, the mechanobiological mechanisms affecting material property adaptations during differentiation are not completely understood. We implement a fiber-network reinforced, poroelastic model1 of mesenchymal tissue to introduce an analytical model describing the differentiation of mesenchymal tissue in response to simulated applications of tensile stress and fluid pressure.
METHODS: Using a time-dependent algorithm (Fig. 1), we simulate changes in three material properties of differentiating mesenchymal tissue: tensile elastic modulus (Et), compressive aggregate modulus (HA), and permeability (k). In this approach, fluid pressure and tensile strain regulate changes in k, HA, and Et in differentiating tissue through their effects on proteoglycan synthesis and collagen fibrillogenesis. Fluid pressure causes an increase in both proteoglycan and type II collagen synthesis, resulting in a decrease in k and increase in HA due to the hydrophilic nature and large size of the aggregating proteoglycans. It further causes a slight increase in Et due to the formation of type II collagen and increased aggregate modulus. Tensile strain increases collagen formation, resulting in an increase in Et due to the elevated number, size, and cross-linking of collagen fibers and a decrease in k due to the increased flow path length.
RESULTS (Table I): The simulations predicted the largest increases in tensile elastic modulus during differentiation into fibrous tissue and the smallest with differentiation into articular cartilage. Final permeabilities exhibited a reverse trend from tensile elastic moduli results with articular cartilage having the highest permeability and fibrous tissue the lowest. The aggregate modulus exhibited no change during differentiation into fibrous tissue but attained its maximum value during differentiation into articular and fibrocartilage.
DISCUSSION: We have presented a computational approach for simulating the effect of mechanics on material property adaptations during mesenchymal tissue differentiation. Our algorithm calculates final values of tensile elastic modulus, aggregate modulus, and permeability for articular cartilage, fibrocartilage, and fibrous tissue that are consistent with what has been observed in experimental studies. Our time-dependent model provides a framework for describing material property adaptations during the full process of mesenchymal tissue differentiation and provides principles to help explain the formation of different types of soft skeletal tissue during this process.
REFERENCES: 1) Li et al (1999) Clin Bio 673-682