Length-scale mediated differential adhesion of mammalian cells and microbes

Surfaces of implantable biomedical devices are increasingly engineered to promote their interactions with tissue. However, surfaces that stimulate desirable mammalian cell adhesion, spreading, and proliferation also enable microbial colonization. The biomaterials-associated infection that can result is now a critical clinical problem. We have identified an important mechanism to create a surface that can simultaneously promote healing while reducing the probability of infection. Surfaces are created with submicrometer-sized, non-adhesive microgels patterned on an otherwise cell-adhesive surface. Quantitative force measurements between a staphylococcus and a patterned surface show that the adhesion strength decreases significantly at inter-gel spacings comparable to bacterial dimensions. Time-resolved flow-chamber measurements show that the microbial deposition rate dramatically decreases at these same spacings. Importantly, the adhesion and spreading of osteoblast-like cells is preserved despite the sub-cellular non-adhesive surface features. Since such length-scale-mediated differential interactions do not rely on antibiotics, this mechanism can be particularly significant in mitigating biomaterials-associated infection by antibiotic-resistant bacteria such as MRSA. To create biomaterials surfaces that promote mammalian cell adhesion while inhibiting microbial colonization, cell-adhesive surfaces are patterned with submicrometer-sized, non-adhesive microgels. The inter-gel spacing is varied and it is found that, at inter-gel spacings comparable to microbial dimensions (∼1-2 μm), the rate of microbial adhesion significantly drops while the adhesion and spreading of osteoblast-like cells is preserved. Such length-scale-mediated differential cell adhesion is a new antibiotic-free mechanism with which to promote healing while reducing the probability of biomaterials-associated infection.