The effects of liquid crystal-based composite substrates on cell functional responses of human umbilical cord-derived mesenchymal stem cells by mechano-regulatory process.

Physical properties of extracellular matrix, including elasticity and microstructure, have been considered as important factors inducing stem cell differentiation. This study developed a novel type of liquid crystal-based matrix by combining the elastic property of polyurethane with viscoelastic liquid crystal to generate a soft elastic response resembling physical microenvironment of stem cell niche, and explored the mechano-driving cell behaviors. Addition of varying liquid crystal concentration (10 wt%, 30 wt% and 50 wt%) had great effects on surface morphology and elastic modulus of liquid crystal/ polyurethane composite substrates. Changes in microstructure and elastic modulus of the substrates could cause intense cell responses that influenced cell properties, including proliferation, adhesion, and osteogenic differentiation. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) cultured on both liquid crystal-10/polyurethane and liquid crystal-30/polyurethane substrates exhibited higher viability, more actin filament, and larger spreading area while liquid crystal-50/polyurethane substrates seemed not to favor cell attachment and spreading. Alkaline phosphatase activity and calcium deposition were significantly improved with hUC-MSCs on both liquid crystal-10/ polyurethane and liquid crystal-30/ polyurethane substrates, and the maximal alkaline phosphatase activity was observed in liquid crystal-10/ polyurethane while the lowest in liquid crystal-50/ polyurethane. Osteopontin was upregulated to a high level in both liquid crystal-10/ polyurethane and liquid crystal-30/ polyurethane groups after 14 days culturing; the maximal expression of osteocalcin and related transcription factor 2 were found in liquid crystal-10/ polyurethane group on day 21. Our findings revealed that hUC-MSCs could intensely sense the bioactive patterns and soft-matter feature of liquid crystal domains and subsequently modulated cell behaviors, which may prove useful in the development of new class of biomaterials for applications in tissue engineering and regenerative medicine.