Micro-scale strain transfer in fiber-reinforced native tissues and cell-seeded aligned nanofibrous scaffolds

Mechanical signals are essential in regulating cell functions such as viability, differentiation, proliferation, and extracellular matrix (ECM) production in load-bearing tissues. However, the current understanding of how macroscopic tissue level strain is transferred to cells is confounded by the highly variable strain fields that arise within the ECM of both native and cell-seeded nanofibrous scaffolds. Moreover, it is unclear how these transmission mechanisms relate to native load bearing tissues. The current study investigates how applied macroscopic tensile strain is transferred to the intercellular ECM and cell nuclei in meniscus, tendon, single lamellar AF, and MSC-seeded scaffolds. The mean microscopic Lagrangian and principal strains in the loading direction (E₂₂ and e₂) of all native tissues and scaffolds were attenuated from the applied strains by 50% and 30-40% respectively. In aligned scaffold, a significant correlation was observed between the mean nuclear strain and E₂₂ (r²=0.98), where 100% of E₂₂ transferred to nuclei. Less pronounced strain attenuation in scaffolds compared to native tissues is likely due to more homogeneous microstructure and lack of ECM. In addition, the presence of pericellular matrix in native tissues, along with dense ECM, may shield and regulate strain transfer from the ECM to the subcellular space.