Abstract
Synthetic hydrogels can be used as scaffolds that not only favor endothelial cells (ECs) proliferation but also manipulate the behaviors and functions of the ECs. In this review paper, the effect of chemical structure, Young’s modulus (E) and zeta potential (ζ) of synthetic hydrogel scaffolds on static cell behaviors, including cell morphology, proliferation, cytoskeleton structure and focal adhesion, and on dynamic cell behaviors, including migration velocity and morphology oscillation, as well as on EC function such as anti-platelet adhesion, are reported. It was found that negatively charged hydrogels, poly(2-acrylamido-2-methylpropanesulfonic sodium) (PNaAMPS) and poly(sodium p-styrene sulphonate) (PNaSS), can directly promote cell proliferation, with no need of surface modification by any cell-adhesive proteins or peptides at the environment of serum-containing medium. In addition, the Young’s modulus (E) and zeta potential (ζ) of hydrogel scaffolds are quantitatively tuned by copolymer hydrogels, poly(NaAMPS-co-DMAAm) and poly(NaSS-co-DMAAm), in which the two kinds of negatively charged monomers NaAMPS and NaSS are copolymerized with neutral monomer, N,N-dimethylacrylamide (DMAAm). It was found that the critical zeta potential of hydrogels manipulating EC morphology, proliferation, and motility is ζ critical = −20.83 mV and ζ critical = −14.0 mV for poly(NaAMPS-co-DMAAm) and poly(NaSS-co-DMAAm), respectively. The above mentioned EC behaviors well correlate with the adsorption of fibronectin, a kind of cell-adhesive protein, on the hydrogel surfaces. Furthermore, adhered platelets on the EC monolayers cultured on the hydrogel scaffolds obviously decreases with an increase of the Young’s modulus (E) of the hydrogels, especially when E > 60 kPa. Glycocalyx assay and gene expression of ECs demonstrate that the anti-platelet adhesion well correlates with the EC-specific glycocalyx. The above investigation suggests that understanding the relationship between physic-chemical properties of synthetic hydrogels and cell responses is essential to design optimal soft and wet scaffolds for tissue engineering.
Highlights
In order to survive and proliferation, anchorage dependent cells must adhere to and spread on a scaffold
It is naturally considered that if cells are cultivated on the hydrogel scaffolds that have viscoelastic 3D structure similar to extracellular matrix (ECM), the cells will live in the environment that is more similar to living body than on other hard and dry scaffolds, such as glass and tissue culture polystyrene (TCPS)
The results suggested that the glycocalyx of cultured endothelial cells (ECs) modulates platelet compatibility, and the amount of glycocalyx secreted by ECs dependents on the chemical structure and Young's modulus (E) of hydrogel scaffolds
Summary
In order to survive and proliferation, anchorage dependent cells must adhere to and spread on a scaffold. Over the past 10 years, there is a dramatic increase in the studies of cell behaviors on the synthetic hydrogels This is because: (i) their structural and physic-chemical properties, such as. The simple and well-defined chemical structure and high purity of synthetic hydrogels make it relatively easier for explaining the mechanism of interaction between cultured cell and scaffolds [5,6]. Even though the amazing physical-chemical properties of synthetic hydrogels that attract scientists to design hydrogels suitable for cell culture scaffolds, comparing with the commercially available naturally derived collagen gel and MatrigelTM (a mixture of murine sarcoma-derived ECM) [7], cell proliferation does not occur spontaneously on many neutral synthetic hydrogels, which is one of the significant disadvantages as cell cultivation scaffold. Our recent progresses on manipulate EC behaviors and functions by the physic-chemical properties of the synthetic hydrogels, including the effect of chemical structure of the hydrogels on cell proliferation behavior and platelet adhesion on the cultured EC monolayer, effect of Zeta potential of hydrogels on static cell behaviors, including cell morphology, proliferation, cytoskeletal structure and focal adhesion, and on dynamic cell behaviors, including migration velocity and morphology oscillation, as well as on EC function, anti-platelet adhesion, will be introduced
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