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

Abstract

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 sixarm 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.

Applications of Stimuli-Responsive Hydrogels in Bone and Cartilage Regeneration

“…The breakage and formation of disulfide bonds can trigger a reversible modification of the cross-linked structure, resulting in the reversible transformation of the elastic module. Using that hydrogel as the substrate for rBMSC culture displayed great osteoinduction under various redox stimulations [ 85 ]. In addition, Yang et al [ 86 ] synthesized a disulfide-containing, 4-armed-PEG-based scaffold loaded with rhBMP-2 that can be controlled by disulfide bond breakage in the presence of reductive GSH or other oxidative species.…”

Cellular feedback to organotelluranes displays modulation of antioxidant proteins gene expression

“…The pathway of redox-sensitive gene expression involves agents acting as sensors, transducers and effectors. [28][29][30][31] The redox state of cysteine residues is a key signal for a cellular gene expression in response to loss of redox homeostasis. In this regard, distinct oxidative states of cysteine residues elicit specific responses in cells.…”