Medical implants have opened up more possibilities in clinical medicine, while they may lead to severe complications due to biofilm formed by bacteria. Understanding the bacterial response mechanism to the material's stiffness is critical to preventing biofilm formation. This study used Staphylococcus aureus , one of the most common clinical pathogens, to explore the response mechanism. Based on the results, bacteria adhere more efficiently with lower membrane potential on stiff hydrogels than soft hydrogels. Combining experiments and molecular dynamics simulations, we found that the Arsenical pump membrane protein (ArsB) of S. aureus was upregulated on stiff hydrogels and can modulate the bacterial membrane potential and adhesion. The interface membrane curvature was the main morphology difference between bacteria on soft and stiff hydrogels. With the more significant membrane deformation of the bacteria on stiff hydrogels, we demonstrated that the changes in membrane curvature could open the ArsB ion channel. Finally, we screened the ArsB inhibitory drug Rapamycin and verified that Rapamycin-loaded hydrogels could efficiently prevent bacterial adhesion. It can be a way of inhibiting bacterial adhesion during biofilm formation and provide directions for the design of future medical materials.
Stiffness is an important physical property of biomaterials that determines stem cell fate. Guiding stem cell differentiation via stiffness modulation has been considered in tissue engineering. However, the mechanism by which material stiffness regulates stem cell differentiation into the tendon lineage remains controversial. Increasing evidence demonstrates that immune cells interact with implanted biomaterials and regulate stem cell behaviors via paracrine signaling; however, the role of this mechanism in tendon differentiation is not clear. In this study, polydimethylsiloxane (PDMS) substrates with different stiffnesses are developed, and the tenogenic differentiation of mesenchymal stem cells (MSCs) exposed to different stiffnesses and macrophage paracrine signals is investigated. The results reveal that lower stiffnesses facilitates tenogenic differentiation of MSCs, while macrophage paracrine signals at these stiffnesses suppress the differentiation. When exposed to these two stimuli, MSCs still exhibit enhanced tendon differentiation, which is further elucidated by global proteomic analysis. Following subcutaneous implantation in rats for 2 weeks, soft biomaterial induces only low inflammation and promotes tendon-like tissue formation. In conclusion, the study demonstrates that soft, rather than stiff, material has a greater potential to guide tenogenic differentiation of stem cells, which provides comprehensive evidence for optimized bioactive scaffold design in tendon tissue engineering.
危险品化学品经营许可证（带存储）