Osteocytes are mechanosensitive bone cells, but little is known about their effects on tumor cells in response to mechanical stimulation. We treated breast cancer cells with osteocyte-derived conditioned medium(CM) an...Osteocytes are mechanosensitive bone cells, but little is known about their effects on tumor cells in response to mechanical stimulation. We treated breast cancer cells with osteocyte-derived conditioned medium(CM) and fluid flow-treated conditioned medium(FFCM) with 0.25 Pa and 1 Pa shear stress. Notably, CM and FFCM at 0.25 Pa induced the mesenchymal-to-epithelial transition(MET), but FFCM at 1 Pa induced the epithelial-to-mesenchymal transition(EMT). This suggested that the effects of fluid flow on conditioned media depend on flow intensity. Fluorescence resonance energy transfer(FRET)-based evaluation of Src activity and vinculin molecular force showed that osteopontin was involved in EMT and MET switching. A mouse model of tumorinduced osteolysis was tested using dynamic tibia loadings of 1, 2, and 5 N. The low 1 N loading suppressed tumor-induced osteolysis, but this beneficial effect was lost and reversed with loads at 2 and 5 N, respectively. Changing the loading intensities in vivo also led to changes in serum TGFβ levels and the composition of tumor-associated volatile organic compounds in the urine.Collectively, this study demonstrated the critical role of intensity-dependent mechanotransduction and osteopontin in tumorosteocyte communication, indicating that a biophysical factor can tangibly alter the behaviors of tumor cells in the bone microenvironment.展开更多
Surfaces with hydrophilic and antimicrobial properties are very attractive for cardio-vascular device-associated applications.The aim of this study was to prepare and coat a hydrophilic polymer containing a functional...Surfaces with hydrophilic and antimicrobial properties are very attractive for cardio-vascular device-associated applications.The aim of this study was to prepare and coat a hydrophilic polymer containing a functional group capable of forming triazole functionality onto the surface of polyurethane(PU).The modified surfaces were assessed with cell adhesion,bacterial adhesion and bacterial viability.Mouse fibroblast cells(NIH-3T3)and three bacterial species were used for assessment.The results showed that the modified surface not only exhibited a significant reduction in cell adhesion with a 25%-59%decrease to mouse fibroblast but also showed a sig-nificant reduction in bacterial attachment with 26%-67%,24%-61%and 23%-57%decrease to Staphylococcus aureus,Escherichia coli and Pseudomonas aeruginosa,respectively,as compared with original PU.Furthermore,the polymer-modified surface exhibited a significant antibacterial function by inhibiting bacterial growth with reduction of 49%-84%,44%-79%and 53%-79%to S.aureus,E.coli and P.aeru-ginosa,respectively,as compared with original PU.These results indicate that covalent polymer attachment enhanced the antibacterial and antifouling properties of the PU surface.展开更多
Hydrophilic polymers are very useful in biomedical applications.In this study,biocom-patible polyethylene glycol(PEG)and polyvinylpyrrolidone(PVP)polymers end-capped with succinimidyl groups were either modified or sy...Hydrophilic polymers are very useful in biomedical applications.In this study,biocom-patible polyethylene glycol(PEG)and polyvinylpyrrolidone(PVP)polymers end-capped with succinimidyl groups were either modified or synthesised and attached to poly-vinylchloride surfaces.The modified surfaces were evaluated with cell adhesion and bacterial adhesion.3T3 mouse fibroblast cells and three bacteria species were used to evaluate surface adhesion activity.Results showed that the modified surface exhibited significantly reduced 3T3 cell adhesion with a 50%-69%decrease for PEG and a 64%-81%for PVP,as compared to unmodified polyvinylchloride.The modified surface also showed significantly reduced bacterial attachment with 22%-78%,18%-76%and 20%-75%decrease for PEG and 22%-76%,18%-76%and 20%-73%for PVP to Staphy-lococcus aureus,Escherichia coli and Pseudomonas aeruginosa,respectively,as compared to unmodified polyvinylchloride.It seems that an appropriate chain length or molecular weight(neither the longest nor the shortest chain length)determines the lowest cell and bacterial adhesion in terms of PEG.On the other hand,a mixture of polymers with different chain lengths exhibited the lowest cell and bacterial adhesion in terms of PVP.展开更多
基金supported in part by funds from the breast cancer advocacy group 100 Voices of Hope, as well as by NIHR01 AR52144, R03 CA238555 (HY) and R01 AR053237 (AGR).NIHR01 AR52144,R03 CA238555 (HY) and R01 AR053237 (AGR)100 Voices of Hope (HY)。
文摘Osteocytes are mechanosensitive bone cells, but little is known about their effects on tumor cells in response to mechanical stimulation. We treated breast cancer cells with osteocyte-derived conditioned medium(CM) and fluid flow-treated conditioned medium(FFCM) with 0.25 Pa and 1 Pa shear stress. Notably, CM and FFCM at 0.25 Pa induced the mesenchymal-to-epithelial transition(MET), but FFCM at 1 Pa induced the epithelial-to-mesenchymal transition(EMT). This suggested that the effects of fluid flow on conditioned media depend on flow intensity. Fluorescence resonance energy transfer(FRET)-based evaluation of Src activity and vinculin molecular force showed that osteopontin was involved in EMT and MET switching. A mouse model of tumorinduced osteolysis was tested using dynamic tibia loadings of 1, 2, and 5 N. The low 1 N loading suppressed tumor-induced osteolysis, but this beneficial effect was lost and reversed with loads at 2 and 5 N, respectively. Changing the loading intensities in vivo also led to changes in serum TGFβ levels and the composition of tumor-associated volatile organic compounds in the urine.Collectively, this study demonstrated the critical role of intensity-dependent mechanotransduction and osteopontin in tumorosteocyte communication, indicating that a biophysical factor can tangibly alter the behaviors of tumor cells in the bone microenvironment.
基金Indiana University-Purdue University IndianapolisMajmaah University。
文摘Surfaces with hydrophilic and antimicrobial properties are very attractive for cardio-vascular device-associated applications.The aim of this study was to prepare and coat a hydrophilic polymer containing a functional group capable of forming triazole functionality onto the surface of polyurethane(PU).The modified surfaces were assessed with cell adhesion,bacterial adhesion and bacterial viability.Mouse fibroblast cells(NIH-3T3)and three bacterial species were used for assessment.The results showed that the modified surface not only exhibited a significant reduction in cell adhesion with a 25%-59%decrease to mouse fibroblast but also showed a sig-nificant reduction in bacterial attachment with 26%-67%,24%-61%and 23%-57%decrease to Staphylococcus aureus,Escherichia coli and Pseudomonas aeruginosa,respectively,as compared with original PU.Furthermore,the polymer-modified surface exhibited a significant antibacterial function by inhibiting bacterial growth with reduction of 49%-84%,44%-79%and 53%-79%to S.aureus,E.coli and P.aeru-ginosa,respectively,as compared with original PU.These results indicate that covalent polymer attachment enhanced the antibacterial and antifouling properties of the PU surface.
文摘Hydrophilic polymers are very useful in biomedical applications.In this study,biocom-patible polyethylene glycol(PEG)and polyvinylpyrrolidone(PVP)polymers end-capped with succinimidyl groups were either modified or synthesised and attached to poly-vinylchloride surfaces.The modified surfaces were evaluated with cell adhesion and bacterial adhesion.3T3 mouse fibroblast cells and three bacteria species were used to evaluate surface adhesion activity.Results showed that the modified surface exhibited significantly reduced 3T3 cell adhesion with a 50%-69%decrease for PEG and a 64%-81%for PVP,as compared to unmodified polyvinylchloride.The modified surface also showed significantly reduced bacterial attachment with 22%-78%,18%-76%and 20%-75%decrease for PEG and 22%-76%,18%-76%and 20%-73%for PVP to Staphy-lococcus aureus,Escherichia coli and Pseudomonas aeruginosa,respectively,as compared to unmodified polyvinylchloride.It seems that an appropriate chain length or molecular weight(neither the longest nor the shortest chain length)determines the lowest cell and bacterial adhesion in terms of PEG.On the other hand,a mixture of polymers with different chain lengths exhibited the lowest cell and bacterial adhesion in terms of PVP.
