Mesenchymal stem cells on polyrotaxane surfaces underwent enhanced osteoblast and adipocyte differentiation. Two independent parameters, high molecular mobility and negative charge on the surfaces, may not offset the effect to promote both differentiation.
The role of molecular mobility on polyrotaxane surfaces was investigated in epithelial cell–cell adhesion. The polyrotaxane surfaces with higher mobility induced cytoplasmic YAP localization, leading to stronger cell–cell adhesion.
Hydrogels are promising materials in tissue engineering scaffolds for healing and regenerating damaged biological tissues. Previously, we developed supramolecular hydrogels using polyrotaxane (PRX), consisting of multiple cyclic molecules threaded by an axis polymer for modulating cellular responses. However, since hydrogels generally have a large amount of water, their adhesion to tissues is extremely weak. Herein, we designed a bilayered hydrogel with a PRX layer and a collagen layer (PRX/collagen hydrogel) to achieve rapid and strong adhesion to the target tissue. The PRX/collagen hydrogel was fabricated by polymerizing PRX crosslinkers in water with placement of a collagen sponge. The differences in components between the PRX and collagen layers were analyzed using Fourier transform infrared spectroscopy (FT-IR). After confirming that the fibroblasts adhered to both layers of the PRX/collagen hydrogels, the hydrogels were implanted subcutaneously in mice. The PRX hydrogel without collagen moved out of its placement site 24 h after implantation, whereas the bilayer hydrogel was perfectly adherent at the site. Together, these findings indicate that the bilayer structure generated using PRX and collagen may be a rational design for performing anisotropic adhesion.
Cancer cells recognize physical cues transmitted from the surrounding microenvironment, and accordingly alter the migration and chemosensitivity. Cell adhesive biomaterials with tunable physical properties can contribute to the understanding of cancer cell responses, and development of new cancer therapies. Previously, it was reported that polyrotaxane‐based surfaces with molecular mobility effectively modulate cellular functions via the yes‐associated protein (YAP)‐related signaling pathway. In the present study, the impact of molecular mobility of polyrotaxane surfaces on the migration and chemosensitivity of lung (A549), pancreatic (BxPC‐3), and breast cancer (MDA‐MB‐231) cell lines is investigated, and it is found that the cellular spreading of adherent A549 and BxPC‐3 cells and nuclear YAP translocation are promoted on low‐mobility surfaces, suggesting that cancer cells alter their subcellular YAP localization in response to molecular mobility. Furthermore, low‐mobility surfaces suppress cellular migration more than high‐mobility surfaces. Additionally, low‐mobility surfaces promote the cisplatin chemosensitivity of each cancer cell line to a greater extent than high‐mobility surfaces. These results suggest that the molecular mobility of polyrotaxane surfaces suppresses cellular migration and enhances chemosensitivity via the subcellular translocation of YAP in cancer cells. Biointerfaces based on polyrotaxanes can thus be a new platform for elucidating cancer cell migration and chemoresistance mechanisms.
Polyrotaxane is a supramolecular assembly consisting of multiple cyclic molecules threaded by a linear polymer. One of the unique properties of polyrotaxane is molecular mobility, cyclic molecules moving along the linear polymer. Molecular mobility of polyrotaxane surfaces affects cell spreading, differentiation, and other cell‐related aspects through changing subcellular localization of yes‐associated proteins (YAPs). Subcellular YAP localization is also related to cell senescence derived from oxidative stress, which is known to cause cancer, diabetes, and heart disease. Herein, the effects of polyrotaxane surface molecular mobility on subcellular YAP localization and cell senescence following H2O2‐induced oxidative stress are evaluated in human mesenchymal stem cells (HMSCs) cultured on polyrotaxane surfaces with different molecular mobilities. Oxidative stress promotes cytoplasmic YAP localization in HMSCs on high‐mobility polyrotaxane surfaces; however, low‐mobility polyrotaxane surfaces more effectively maintain nuclear YAP localization, exhibiting lower senescence‐associated β‐galactosidase activity and senescence‐related gene expression and DNA damage than that seen with the high‐mobility surfaces. These results suggest that the molecular mobility of polyrotaxane surfaces regulates subcellular YAP localization, thereby protecting HMSCs from oxidative stress‐induced cell senescence. Applying the molecular mobility of polyrotaxane surfaces to implantable scaffolds can provide insights into the prevention and treatment of diseases caused by oxidative stress.
Surface properties of biomaterials affect the morphologies and inflammatory responses of macrophages. Recently, biomaterial design utilizing these properties has been explored to build a scaffold for balancing the immune system in vivo. In the present study, polyrotaxane surfaces with different functional groups including methyl, amino, and sulfo groups are utilized to clarify the effect of molecular mobility and zeta potential of these surfaces on RAW264.7 macrophage responses. At 24 h post-seeding, the majority of the cells adhere onto each surface, and the initial spreading is suppressed by more negatively-charged polyrotaxane surfaces. From 24 to 48 h of incubation, the spreading areas on the unmodified and methylated surfaces significantly increase, whereas those on the aminated and sulfonated surfaces remain unchanged. These results suggest that the initially cellular spreading process depends on the zeta potential, while the subsequent spreading process is governed by the molecular mobility. After lipopolysaccharide stimulation, the less mobile surfaces induce higher expression of inflammation-related genes than highly mobile surfaces, suggesting that molecular mobility is the main factor modulating the inflammatory activity in macrophages. These findings indicate that the zeta potential and molecular mobility of polyrotaxane surfaces may play independent roles in the sequence of macrophage responses.
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