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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.

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., Optimizing the concentration of different functional peptides on a surface can be a complex process. Here, the authors report on the use of a click immobilization strategy to create gradients of two different functional peptides on a surface to screen different density functions for rapid optimization.

As an effective strategy to develop novel implants with a biomolecule, the efficiency of a copper-catalysed azide-alkyne cycloaddition (CuAAC) urgently requires improvement. Herein, we constructed a facile CuAAC system with catalytic CuSO4/sodium borohydride (CuAAC-Bor). As Cu nanoclusters (CuNCs) formed in situ, they showed stronger efficiency in immobilizing 41 types of peptides on Ti implants than traditional CuAAC with CuSO4/sodium ascorbate. Then, we mechanically revealed the significance of peptide size on CuAAC efficiency by all-atom molecular dynamics simulation and machine learning, and found that larger peptides preferred to adhere to Ti and CuNCs to increase their reaction opportunity. With CuAAC-Bor, HHC36-engineered implants strongly inhibited 5 types of clinical bacteria in vitro and prevented infection in vivo, and RGD-, DGEA-, QK- or YGFGG-engineered implants had high biocompatibilities with HUVECs/hBMSCs in vitro. Moreover, we demonstrated that QK-engineered implants prepared with CuAAC-Bor promoted the osteogenic differentiation of hBMSCs via the PI3K/Akt signalling pathway and triggered angiogenesis and osteogenesis in vivo. Our study shows that this facile and highly efficient CuAAC-Bor system holds high promise for the preparation of novel biomaterial surfaces.

Biomaterial-associated infection (BAI) and delayed osseointegration are two major limitations for orthopeadic titanium implants, which are highly required in clinic implants. Herein, we rationally design a series of novel fusion peptides (FPs) based on HHC36 and BFP1 with different polyethylene glycol (PEG) spacers, and covalently immobilize them onto titanium implants via a one-step reaction between thiol groups and titanium hydroxyl groups. All FP-engineered implants show improved biocompatibility and osteogenic activity with hBMSCs. But interestingly, they display spacer-dependent antimicrobial and anti-inflammatory activities. Specifically, implants engineered with FPs containing no more than 12 units of PEG spacers exhibit strong antimicrobial activity against clinical bacteria (S. aureus, E. coli, P. aeruginosa, S. epidermidis and MRSA) and mediated macrophages transitions towards M2 polarization. However, implants engineered with FPs containing long PEG spacers (24 units) show negligible levels of the abovementioned activities. By all-atom molecular dynamics simulation, we demonstrate that the loss of activity is due to low exposure of antimicrobial sequence (HHC36) and high exposure of PEG. In vivo assays show that optimized FP-engineered implants inhibit S. aureus by 97.89%, while promoting osseointegration. This research provides great potential to resolve BAI and delayed osseointegration issues for orthopeadic implants.