Periodic Dynamic Regulation of MSCs Differentiation on Redox-Sensitive Elastic Switched Substrates

The biomechanical properties of cell culture substrates can affect cell morphology, cytoskeletal structure, and cell differentiation. However, most of the elastic substrates reported to regulate the behavior of stem cells are often limited to model the static surface, such as providing a constant elasticity modulus for the substrates. In this article, we synthesized a redox-sensitive smart hydrogel with a programmed switchover of elastic substrates in response to glutathione (GSH)/oxidizided glutathione (GSSG) concentration change. The hydrogel is made up of a mixture six-arm poly(ethylene glycol)-poly(ε-caprolactone)-3,3'-dithiodipropionic acid gels (6A PECL-SS) and six-arm poly(ethylene glycol)-poly(ε-caprolactone)-acryloyl (6A PECL-AC). Under different redox stimulus (+GSH or +GSSG), the redox-sensitive substrate can act as a cross-linked switch to adjust the elasticity modulus. RT-PCR results based on cell culture evaluation indicate that the reversibly controlled elastic substrates cultured on a flat and microgroove surface exhibited good osteoinduction under different inversion frequencies. Therefore, our results indicate that this redox-responsive substrate has great potential in bone tissue engineering.