Bio-Inspired Self-Adaptive Nanocomposite Array: From Non-antibiotic Antibacterial Actions to Cell Proliferation.

Pathogenic bacterial infection and poor native tissue integration are two major issues encountered by biomaterial implants and devices, which are extremely hard to overcome within a single surface, especially for those without involvement of antibiotics. Herein, a self-adaptive surface that can transform from non-antibiotic antibacterial actions to promotion of cell proliferation is developed by in situ assembly of bacteriostatic 3,3'-diaminodipropylamine (DADP)-doped zeolitic imidazolate framework-8 (ZIF-8) on bio-inspired nanopillars. Initially, the nanocomposite surface shows impressive antibacterial effects, even under severe bacterial infection, due to the combination of mechano-bactericidal activity from a nanopillar structure and bacteriostatic activity contributed by pH-responsive release of DADP. After the complete degradation of the ZIF-8 layer, the refurbished nanopillars not only can still physically rupture bacterial membrane but also facilitate mammalian cell proliferation, due to the obvious difference in cell size. More strikingly, the nanocomposite surface totally avoids the usage of antibiotics, eradicating the potential risk of antimicrobial resistance, and the surface exhibited excellent histocompatibility and lower inflammatory response properties as revealed by in vivo tests. This type of self-adaptive surface may provide a promising alternative for addressing the intractable implant-associated requirements, where antibiotic-free antibacterial activity and native tissue integration are both highly needed.

Bioinspired nanopillar surface for switchable mechano-bactericidal and releasing actions.

Constructing safe and effective antibacterial surfaces has continuously received great attention, especially in healthcare-related fields. Bioinspired mechano-bactericidal nanostructure surfaces could serve as a promising strategy to reduce surface bacterial contamination while avoiding the development of antibiotic resistance. Although effective, these nanostructure surfaces are prone to be contaminated by the accumulation of dead bacteria, inevitably compromising their long-term antibacterial activity. Herein, a bioinspired nanopillar surface with both mechano-bactericidal and releasing actions is developed, via grafting zwitterionic polymer (poly(sulfobetaine methacrylate) (PSBMA)) on ZnO nanopillars. Under dry conditions, this nanopillar surface displays remarkable mechano-bactericidal activity, because the collapsed zwitterionic polymer layer makes no essential influence on nanopillar structure. Once being incubated with aqueous solution, the surface could readily detach the killed bacteria and debris, owing to the swelling of the zwitterionic layer. Consequentially, the surface antibacterial performances can be rapidly and controllably switched between mechano-bactericidal action and bacteria-releasing activity, guaranteeing a long-lasting antibacterial performance. Notably, these collaborative antibacterial behaviors are solely based on physical actions, avoiding the risk of triggering bacteria resistance. The resultant nanopillar surface also enjoys the advantages of substrate-independency and good biocompatibility, offering potential antibacterial applications for biomedical devices and hospital surfaces.

Biocompatible mechano-bactericidal nanopatterned surfaces with salt-responsive bacterial release.

Bio-inspired nanostructures have demonstrated highly efficient mechano-bactericidal performances with no risk of bacterial resistance; however, they are prone to become contaminated with the killed bacterial debris. Herein, a biocompatible mechano-bactericidal nanopatterned surface with salt-responsive bacterial releasing behavior is developed by grafting salt-responsive polyzwitterionic (polyDVBAPS) brushes on a bio-inspired nanopattern surface. Benefiting from the salt-triggered configuration change of the grafted polymer brushes, this dual-functional surface shows high mechano-bactericidal efficiency in water (low ionic strength condition), while the dead bacterial residuals can be easily lifted by the extended polymer chains and removed from the surface in 1 M NaCl solution (high ionic strength conditions). Notably, this functionalized nanopatterned surface shows selective biocidal activity between bacterial cells sand eukaryotic cells. The biocompatibility with red blood cells (RBCs) and mammalian cells was tested in vitro. The histocompatibility and prevention of perioperative contamination activity were verified by in vivo evaluation in a rat subcutaneous implant model. This nanopatterned surface with bacterial killing and releasing activities may open new avenues for designing bio-inspired mechano-bactericidal platforms with long-term efficacy, thus presenting a facile alternative in combating perioperative-related bacterial infection. STATEMENT OF SIGNIFICANCE: Bioinspired nanostructured surfaces with noticeable mechano-bactericidal activity showed great potential in moderating drug-resistance. However, the nanopatterned surfaces are prone to be contaminated by the killed bacterial debris and compromised the bactericidal performance. In this study, we provide a dual-functional antibacterial conception with both mechano-bactericidal and bacterial releasing performances not requiring external chemical bactericidal agents. Additionally, this functionalized antibacterial surface also shows selective biocidal activity between bacteria and eukaryotic cells, and the excellent biocompatibility was tested in vitro and in vivo. The new concept for the functionalized mechano-bactericidal surface here illustrated presents a facile antibiotic-free alternative in combating perioperative related bacterial infection in practical application.

Thermoresponsive Nanostructures: From Mechano-Bactericidal Action to Bacteria Release.

Overuse of antibiotics can increase the risk of notorious antibiotic resistance in bacteria, which has become a growing public health concern worldwide. Featured with the merit of mechanical rupture of bacterial cells, the bioinspired nanopillars are promising alternatives to antibiotics for combating bacterial infections while avoiding antibacterial resistance. However, the resident dead bacterial cells on nanopillars may greatly impair their bactericidal capability and ultimately impede their translational potential toward long-term applications. Here, we show that the functions of bactericidal nanopillars can be significantly broadened by developing a hybrid thermoresponsive polymer@nanopillar-structured surface, which retains all of the attributes of pristine nanopillars and adds one more: releasing dead bacteria. We fabricate this surface through coaxially decorating mechano-bactericidal ZnO nanopillars with thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) brushes. Combining the benefits of ZnO nanopillars and PNIPAAm chains, the antibacterial performances can be controllably regulated between ultrarobust mechano-bactericidal action (∼99%) and remarkable bacteria-releasing efficiency (∼98%). Notably, both the mechanical sterilization against the live bacteria and the controllable release for the pinned dead bacteria solely stem from physical actions, stimulating the exploration of intelligent structure-based bactericidal surfaces with persistent antibacterial properties without the risk of triggering drug resistance.