Biofilm Disruption from within: Light-Activated Molecular Drill-Functionalized Polymersomes Bridge the Gap between Membrane Damage and Quorum Sensing-Mediated Cell Death.

Bacterial biofilms represent an escalating global health concern with the proliferation of drug resistance and hospital-acquired infections annually. Numerous strategies are under exploration to combat biofilms and preempt the development of antibacterial resistance. Among these, mechanical disruption of biofilms and enclosed bacteria presents a promising avenue, aiming to induce membrane permeabilization and consequent lethal damage. Herein, we introduce a hemithioindigo (HTI) motor activated by visible light, capable of disrupting sessile bacteria when integrated into a polymeric vesicle carrier. Under visible light, bacteria exhibited a notable outer membrane permeability, reduced membrane fluidity, and diminished viability following mechanical drilling. Moreover, various genetic responses pertaining to the cell envelope were examined via qRT-PCR, alongside the activation of a self-lysis mechanism associated with phage stress, which was coupled with increases in quorum sensing, demonstrating a potential self-lysis cascade from within. The multifaceted mechanisms of action, coupled with the energy efficiency of mechanical damage, underscore the potential of this system in addressing the challenges posed by pathogenic biofilms.

Conductive Polyisocyanide Hydrogels Inhibit Fibrosis and Promote Myogenesis.

Reliable in vitro models closely resembling native tissue are urgently needed for disease modeling and drug screening applications. Recently, conductive biomaterials have received increasing attention in the development of in vitro models as they permit exogenous electrical signals to guide cells toward a desired cellular response. Interestingly, they have demonstrated that they promote cellular proliferation and adhesion even without external electrical stimulation. This paper describes the development of a conductive, fully synthetic hydrogel based on hybrids of the peptide-modified polyisocyanide (PIC-RGD) and the relatively conductive poly(aniline-co-N-(4-sulfophenyl)aniline) (PASA) and its suitability as the in vitro matrix. We demonstrate that incorporating PASA enhances the PIC-RGD hydrogel's electroactive nature without significantly altering the fibrous architecture and nonlinear mechanics of the PIC-RGD network. The biocompatibility of our model was assessed through phenotyping cultured human foreskin fibroblasts (HFF) and murine C2C12 myoblasts. Immunofluorescence analysis revealed that PIC-PASA hydrogels inhibit the fibrotic behavior of HFFs while promoting myogenesis in C2C12 cells without electrical stimulation. The composite PIC-PASA hydrogel can actively change the cell fate of different cell types, providing an attractive tool to improve skin and muscle repair.

Unveiling the Antifouling Potential of Stabilized Poly(phosphorus ylides).

Zwitterionic polymers have emerged as highly attractive building blocks for antifouling coatings in biomedical applications. Notably, these polymers offer effective alternatives to the widely used poly(ethylene glycol) (PEG), which has raised concerns regarding its immunotoxicity and the development of PEG-specific antibodies. Polymeric ylides, a largely overlooked class of zwitterionic polymers, have been reported as effective antifouling scaffolds. However, the reported subclasses, poly(sulfur ylides) and N-oxides, lack structural diversity and chemical variability. In this study, we present the synthesis and characterization of polymeric phosphorus ylides as an unexplored class of poly(ylides) with significantly increased structural diversity, which is of high value when designing future ylide-based antifouling materials. Our findings demonstrate that, owing to their low dipole moments and hydration layers, these polymeric phosphorus ylides significantly reduce bacterial attachment. Furthermore, we observe selective toxicity toward bacteria rather than mammalian cells. The bactericidal nature of poly(phosphorus ylides), coupled with their expanded chemical space, provides a distinct advantage over existing materials, including zwitterionic polymers from betaine scaffolds. We anticipate that these unexplored structures will broaden the scope of antifouling applications for poly(ylides).

Porous Polymersomes as Carriers for Silver Nanoparticles and Nanoclusters: Advantages of Compartmentalization for Antimicrobial Usage.

The global threat to public health posed by antibiotic-resistant bacterial infections requires the exploration of innovative approaches. Nanomaterials, particularly silver nanoparticles (AgNPs) and nanoclusters (AgNCs), have emerged as potential solutions to address the pressing issue of a bacterial healthcare crisis. However, the high cytotoxicity levels and low stability associated with AgNPs and AgNCs limit their applicability. To overcome these challenges, AgNCs and AgNPs were synthesized in the presence of porous polymersomes, resulting in a compartmentalized system that enhances stability, reduces cytotoxicity, and maintains high antimicrobial activity. The encapsulated particles exhibit a distribution of silver components on both the surface and the core, which is confirmed through the analysis of surface charge and center of mass. Moreover, our investigation demonstrates improved stability of the nanoparticles and nanoclusters upon entrapment in the porous system, as evidenced by the ion release assay. The antimicrobial effectiveness of porous polymersomes containing AgNPs and AgNCs was demonstrated by visualizing the biofilms and quantifying the penetration depth. Furthermore, cytotoxicity studies showed that compartmentalization increases cell compatibility for AgNC-based systems, showcasing the many advantages this system holds.

Zwitterionic Polymeric Sulfur Ylides with Minimal Charge Separation Open a New Generation of Antifouling and Bactericidal Materials.

Zwitterionic polymers are widely employed hydrophilic building blocks for antifouling coatings with numerous applications across a wide range of fields, including but not limited to biomedical science, drug delivery and nanotechnology. Zwitterionic polymers are considered as an attractive alternative to polyethylene glycol because of their biocompatibility and effectiveness to prevent formation of biofilms. To this end, zwitterionic polymers are classified in two categories, namely polybetaines and polyampholytes. Yet, despite a fundamental interest to drive the development of new antifouling materials, the chemical composition of zwitterionic polymer remains severely limited. Here, we show that poly(sulfur ylides) that belong to the largely overlooked class of poly(ylides), effectively prevent the formation of biofilms from pathogenic bacteria. While surface energy analysis reveals strong hydrogen-bond acceptor capabilities of poly(sulfur ylide), membrane damage of pathogenic bacteria induced by poly(sulfur ylides) indicates toxicity towards bacteria while not affecting eucaryotic cells. Such synergistic effect of poly(sulfur ylides) offers distinct advantages over polyethylene glycol when designing new antifouling materials. We expect that our findings will pave the way for the development of a range of ylide-based materials with antifouling properties that have yet to be explored, opening up new directions at the interface of chemistry, biology, and material science.