Despite the countless lives saved by the discovery of antibiotics, the emergence of antibiotic-resistant bacteria has emerged as a further issue in modern medicine. To avoid or reduce the overuse of antibiotics in antibacterial treatments, various strategies are currently being developed to improve conventional therapies and enhance sterilization efforts. The common goal of these strategies is to improve efficacy or function via an antibacterial mechanism different from that of antibiotics by enhancing the antibacterial and biological properties while reducing the risk of drug resistance. In addition to efficacy, biosafety is a key factor in designing antibacterial treatments because ideally, antibacterial treatment should eliminate bacteria without harming the host body. Meanwhile, bacterial infections can occur at different sites of the human body, where the host cells and commensal microbiota vary from case to case. Hence, a bio-adaptive concept should be established to ensure the biocompatibility of antibacterial strategies in different application scenarios. In this thesis, bio-adaptive antibacterial strategies are implemented to treat bacterial infections in three types of application environments, including peri-implant tissues, skin-attached devices, and the vaginal tract.

Implant-related infections represent serious post-surgery complications and can compromise the intended functions of artificial implants, leading to surgical failure and even amputation in severe cases. Various strategies have been proposed to endow bone implants with desirable antibacterial properties, though most inevitably lead to side effects detrimental to normal tissues. Adjusting the content of antimicrobials is the first approach presented herein to treat implant-related infections. Silver (Ag) is an excellent antibacterial agent, but achieving the optimal concentration is critical because excessive Ag is detrimental to human health. In the first project, electrochemical polymerization is carried out to fabricate polypyrrole (PPy) coatings, and Ag ions are introduced by plasma immersion ion implantation (PIII). The optimal Ag ion fluence is determined by monitoring the antibacterial efficiency and cytotoxicity. Our results show that the optimal balance between antibacterial ability and cytocompatibility can be attained from sample Ti-PPy@Ag-4 implanted with an Ag ion fluence of 4 × 10¹⁶ ions cm⁻². In addition to retaining good cytocompatibility, 92% of the bacterium Staphylococcus aureus (S. aureus) can be eliminated. The intricate balance between antibacterial effects and biocompatibility arises from the levels of intracellular reactive oxygen species (ROS) in S. aureus and MC3T3-E1 osteoblasts on Ti-PPy@Ag-4. The antibacterial capability and biocompatibility are verified by the subcutaneous infection model in rats in vivo. The results reveal a bio-adaptive strategy to improve the bacterial resistance of polymers such as PPy while not compromising the inherent biosafety of the materials.

In the second project, a multifunctional bone implant is designed to function in conjunction with sequential photothermal mediation, which can deliver antibacterial therapy (<50 °C) in the early stages and foster subsequent bone regeneration (40-42 °C). Black phosphorus nanosheets (BPs) are coordinated with zinc sulfonate ligands (ZnL₂), and the ZnL₂-BPs are integrated into the surface of a hydroxyapatite (HA) scaffold to yield ZnL₂-BPs@HAP. In this design, the BPs produce photothermal effects, and ZnL₂ increases the thermal sensitivity of peri-implant bacteria by inducing envelope stress. The mild temperature improves the biosafety of the antibacterial photothermal treatment, and furthermore, the gradual release of Zn²⁺ and PO₄^3– from the scaffold facilitates osteogenesis in the subsequent bone healing stage. This bio-adaptive strategy not only reduces tissue damage from the antibacterial photothermal treatment but also promotes tissue regeneration after eliminating the bacterial infection.

Bacterial contamination leads to property degeneration in skin-attached devices. However, the power generated by flexible wearable devices (FWDs) is typically insufficient to eradicate bacteria, and high-power electrification may damage the skin tissue in contact with the devices. Many conventional antibacterial strategies are also unsuitable for flexible and wearable applications because of the strict mechanical and electrical requirements. In the third project, PPy, a conductive polymer with a high mass density, is used to form a nanostructured surface on FWDs for antibacterial purposes. The conductive films with PPy nanorods (PNRs) sterilize 98.2 ± 1.6% of S. aureus and 99.6 ± 0.2% of Escherichia coli (E. coli) upon mild electrification (1 V). The bactericidal activity stems from membrane stress produced by the PNRs and membrane depolarization induced by electrical neutralization. Additionally, the PNR films exhibit excellent biosafety and electrical stability. The results represent pioneering work in the fabrication of bio-adaptive antibacterial components for FWDs by comprehensively considering the required conductivity, mechanical properties, and biosafety issues.

The failure to reconstruct the Lactobacillus microbiota is the major reason for the recurrence of vaginal infections. At present, most empiric therapies focus on the efficacy of pathogen elimination but do not sufficiently consider the viability of Lactobacillus. In the fourth project, cotton fibers with a lactic acid-like surface (LC) are fabricated via NaIO₄ oxidation and L-isoserine grafting. The lactic acid analogue chain ends and imine structure of the LC can penetrate cell walls to induce protein cleavage in E. coli and Candida albicans and inhibit vaginal pathogens. Meanwhile, the viability of Lactobacillus acidophilus is unaffected by the LC treatment, thus revealing a selective manner to suppress pathogens as well as providing a positive route to re-establish protective microbiota in the vaginal tract. Moreover, the LC exhibit excellent properties, such as good biosafety, anti-adhesion, water absorption, and weight retention. The strategy proposed here is not only practical but also provides bio-adaptive insights into the treatment of vaginal infections.