RESUMO
Photosensitizers with aggregation-induced emission properties (AIEgens) can produce reactive oxygen species (ROS) under irradiation, showing great potential in the antibacterial field. However, due to the limited molecular skeletons, the development of AIEgens with precisely adjustable antibacterial activity is still a daunting challenge. Herein, a series of AIE nanofibers (AIE-NFs) based on the AIEgen of DTPM as the inner core and rationally designed peptides as bacterial recognition ligands (e.g., antimicrobial peptide (AMP) HHC36, ditryptophan, polyarginine, and polylysine) is developed. These AIE-NFs show precisely adjustable antibacterial behaviors simply by changing the decorated peptides, which can regulate the aggregation and inhibition of different bacteria. By mechanistic analysis, it is demonstrated that this effect can be attributed to the synergistic antibacterial activities of the ROS and the peptides. It is noteworthy that the optimized AIE-NFs, NFs-K18, can efficiently aggregate bacteria to cluster and kill four types of clinical bacteria under irradiation in vitro, inhibit the infection of methicillin-resistant Staphylococcus aureus (MRSA) and promote wound healing in vivo. To the authors' knowledge, this is the first report of AIE-NFs with precisely adjustable antibacterial activity, providing new opportunities for photodynamic therapy (PDT) treatment of infection.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Nanofibras , Fotoquimioterapia , Antibacterianos/química , Bactérias , Peptídeos/farmacologia , Fármacos Fotossensibilizantes/química , Espécies Reativas de OxigênioRESUMO
As one of the most widely used medical devices, sutures face challenges related to surgical site infections (SSIs) and lack of subcutaneous traceability. In the present study, a facile and effective approach using peptide-AIE nanofibers (NFs-K18) to create fluorescent-traceable antimicrobial sutures, which have been applied to four commercially available sutures is developed. The functionalized sutures of PGAS-NFs-K18 and PGLAS-NFs-K18 exhibit fluorescence with excellent penetration from 4 mm chicken breasts. They also demonstrate remarkable stability after 24 h of white light illumination and threading through chicken breasts 10 times. These sutures efficiently generate ROS, resulting in significant suppression of four clinical bacteria, with the highest antimicrobial rate of ≈100%. Moreover, the sutures exhibit favorable hemocompatibility and biocompatibility. In vivo experiments demonstrate that the optimized PGLAS-NFs-K18 suture displays potent antimicrobial activity against MRSA, effectively inhibiting inflammation and promoting tissue healing in both skin wound and abdominal wall wound models, outperforming the commercially available Coated VICRYL Plus Antibacterial suture. Importantly, PGLAS-NFs-K18 exhibits sensitive subcutaneous traceability, allowing for accurate in situ monitoring of its degradation. It is believed that this straightforward strategy offers a new pathway for inhibiting SSIs and monitoring the status of sutures.
Assuntos
Nanofibras , Suturas , Nanofibras/química , Animais , Galinhas , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Peptídeos/química , Peptídeos/farmacologia , Cicatrização/efeitos dos fármacos , Camundongos , Humanos , Infecção da Ferida Cirúrgica/prevenção & controle , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Antibacterianos/farmacologia , Antibacterianos/química , Espécies Reativas de Oxigênio/metabolismoRESUMO
Control over the implant surface functions is highly desirable to enhance tissue healing outcomes but has remained unexplored to adapt to the different service stages. In the present study, we develop a smart titanium surface by orchestrating thermoresponsive polymer and antimicrobial peptide to enable dynamic adaptation to the implantation stage, normal physiological stage and bacterial infection stage. The optimized surface inhibited bacterial adhesion and biofilm formation during surgical implantation, while promoted osteogenesis in the physiological stage. The further temperature increase driven by bacterial infection induced polymer chain collapse to expose antimicrobial peptides by rupturing bacterial membranes, as well as protect the adhered cells from the hostile environment of infection and abnormal temperature. The engineered surface could inhibit infection and promote tissue healing in rabbit subcutaneous and bone defect infection models. This strategy enables the possibility to create a versatile surface platform to balance bacteria/cell-biomaterial interactions at different service stages of implants that has not been achieved before.
Assuntos
Peptídeos , Polímeros , Animais , Coelhos , Aderência Bacteriana , Próteses e Implantes , Bactérias , Materiais Revestidos Biocompatíveis , Titânio/farmacologia , Propriedades de SuperfícieRESUMO
Peptides are widely used for surface modification to develop improved implants, such as cell adhesion RGD peptide and antimicrobial peptide (AMP). However, it is a daunting challenge to identify an optimized condition with the two peptides showing their intended activities and the parameters for reaching such a condition. Herein, we develop a high-throughput strategy, preparing titanium (Ti) surfaces with a gradient in peptide density by click reaction as a platform, to screen the positions with desired functions. Such positions are corresponding to optimized molecular parameters (peptide densities/ratios) and associated preparation parameters (reaction times/reactant concentrations). These parameters are then extracted to prepare nongradient mono- and dual-peptide functionalized Ti surfaces with desired biocompatibility or/and antimicrobial activity in vitro and in vivo. We also demonstrate this strategy could be extended to other materials. Here, we show that the high-throughput versatile strategy holds great promise for rational design and preparation of functional biomaterial surfaces.