Synergetic stimulation of nanostructure and chemistry cues on behaviors of fibroblasts and endothelial cells

Abstract

It has been widely accepted that cell behaviors can be affected by multiple kinds of biomaterial stimulation signals. Although many literatures have focused on studying the multiple biomaterials stimulatory cues in affecting cellular behaviors, systematic studies on the effects of individual and combination of multiple biomaterials stimulatory cues in regulating cellular behaviors and their potential possible mechanisms have rarely been reported. We hypothesized that tissue engineering scaffolds with enhanced bioactivity can be designed if synergetic effects between different kinds of biomaterial stimulation cues in affecting cells behaviors can be found and applied. To prove our concept, in this study, electrospun nanofibers were used to provide structure cues and bioactive glass (BG) ion extracts were used to provide chemistry cues. The effects of single type of electrospun nanofiber structure cues, single type of BG chemical cues and combined application of the two types of stimulatory cues on behaviors of human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs) were evaluated. Results showed that the nanostructure cues of electrospun nanofibers mainly affected cell morphology and cytoskeleton distribution while the chemistry cues of BG ion extracts played important roles in promoting cell proliferation. Both of the electrospun nanofiber structure and BG chemistry cues contributed to cell differentiation, including extracellular matrix synthesis of HDFs and vascularization of HUVECs. Interestingly, when the two kinds of stimulatory cues were applied together, obvious synergetic effects were observed as the combination of the two stimulatory cues showed the strongest stimulation effects on cell differentiation among all groups. Taken together, it is feasible to simultaneously apply two or more kinds of biomaterial stimulation signals to synergistically affect cell behaviors and enhance tissue regeneration, which is critical for instructing the design of tissue engineering scaffolds or biomaterial substrates with improved bioactivity.

Keywords: Chemistry cues; Gene expression and protein secretion; Nanostructure cues; Phenotypic; Synergetic stimulation.