Biocompatible Polycationic Silver Nanocluster-Impregnated PLGA Nanocomposites with Potent Antimicrobial Activity

Ultrasmall cationic silver nanoparticles (AgNPs) have recently emerged as highly potent antimicrobial agents for the treatment of multidrug-resistant bacteria and their biofilms. However, the clinical application of these cationic AgNPs is hampered by their poor stability and high reactivity in solution, leading to uncontrolled release of toxic silver ions. An ideal platform featuring broad-spectrum antibacterial activity and high biocompatibility that prevents overexposure to silver ions, is therefore highly desirable. Herein, we explored a biocompatible and biodegradable polymer, poly(lactic-co-glycolic) acid (PLGA) as an effective carrier for the recently discovered polycationic silver nanoclusters (pAgNCs). These pAgNCs impregnated PLGA nanocomposites (pAgNCs@PLGA) were developed by water-in-oil-in-water (W1/O/W2) emulsion method and characterized by various analytical techniques. Our experimental results reveal that pAgNCs@PLGA had spherical morphology with an average diameter of ∼188 nm and consists of multiple ultrasmall (∼2 nm) pAgNCs at the polymeric core. The minimum inhibitory concentration of pAgNCs for Staphylococcus aureus and Pseudomonas aeruginosa were found to be 6.9 μg/mL. After impregnation within PLGA, the antimicrobial efficacy of our pAgNCs against Staphylococcus aureus and Pseudomonas aeruginosa remained consistent, while the nanocomposites were biocompatible at the minimum inhibitory concentration (MIC) against both bacteria. The pAgNCs@PLGA nanocomposite developed in this work may present a path forward to bring these highly potent pAgNCs into medical practice

Plasma polymerized bio-interface directs fibronectin adsorption and functionalization to enhance “epithelial barrier structure” formation via FN-ITG β1-FAK-mTOR signaling cascade

Background: Transepithelial medical devices are increasing utilized in clinical practices. However, the damage of continuous natural epithelial barrier has become a major risk factor for the failure of epithelium-penetrating implants. How to increase the “epithelial barrier structures” (focal adhesions, hemidesmosomes, etc.) becomes one key research aim in overcoming this difficulty. Directly targeting the in situ “epithelial barrier structures” related proteins (such as fibronectin) absorption and functionalization can be a promising way to enhance interface-epithelial integration. Methods: Herein, we fabricated three plasma polymerized bio-interfaces possessing controllable surface chemistry. Their capacity to adsorb and functionalize fibronectin (FN) from serum protein was compared by Liquid Chromatography-Tandem Mass Spectrometry. The underlying mechanisms were revealed by molecular dynamics simulation. The response of gingival epithelial cells regarding the formation of epithelial barrier structures was tested. Results: Plasma polymerized surfaces successfully directed distinguished protein adsorption profiles from serum protein pool, in which plasma polymerized allylamine (ppAA) surface favored adsorbing adhesion related proteins and could promote FN absorption and functionalization via electrostatic interactions and hydrogen bonds, thus subsequently activating the ITG β1-FAK-mTOR signaling and promoting gingival epithelial cells adhesion. Conclusion: This study offers an effective perspective to overcome the current dilemma of the inferior interface-epithelial integration by in situ protein absorption and functionalization, which may advance the development of functional transepithelial biointerfaces. Graphical Abstract: Tuning the surface chemistry by plasma polymerization can control the adsorption of fibronectin and functionalize it by exposing functional protein domains. The functionalized fibronectin can bind to human gingival epithelial cell membrane integrins to activate epithelial barrier structure related signaling pathway, which eventually enhances the formation of epithelial barrier structure.</p