Abstract
Unlimited self-renewal of stem cells and their multipotency ability lead a great potential in the application of tissue engineering and regenerative medicine. The induction of stem cells can be controlled by multiple factors including physical, chemical and biological cues. By knowing the interaction between stem cells and their vicinity biomimetic microenvironment, we may manipulate stem cell’s fate. In this study, three dimensional porous scaffolds were synthesized by type I collagen (Col) and hyaluronic acid (HA). The elastic modulus (E) of the 3D substrates was modified by adjustable concentrations of 1-ethyl-3(3-dimethylaminopropyl) carbodiimide (EDC) crosslinking agent. The purpose of this study is to investigate the matrix stiffness on the influence of neurogenic differentiation of human mesenchymal stem cells (hMSCs). The mechanical property of Col-HA scaffolds was evaluated and the induction and characterization of hMSCs differentiation toward neural lineages by different substrate stiffness were studied. With different EDC crosslinking concentration, the stiffness of the matrices can be tunable in the ranges of 1 kPa to 10 kPa for soft and stiff substrates. The results found that MSCs tend to differentiate into neuronal lineage in substrate at 1 kPa, while they transform into glial cells in matrix with 10 kPa. The morphology and proliferation behavior of hMSCs were corresponded to substrate stiffness. By using this modifiable matrix, we can investigate the relationship between stem cell behavior and substrate mechanical properties in ECM-based biomimetic 3D scaffolds. A tunable substrate stiffness that would induce hMSCs specifically toward neuronal differentiation may also be very useful as tissue-engineered construct or substitute for delivering hMSCs in brain and spinal cord regeneration.