Antimicrobial peptides (AMPs) are seen as a promising replacement to conventional antibiotics for the prevention of skin wound infections. However, due to the short half-life of AMPs in biological environments, such as blood, their use in clinical applications has been limited. The covalent immobilization of AMPs onto suitable substrates is an effective solution to create contact-killing surfaces with increased long-term stability. In this work, an antimicrobial peptide, RRPRPRPRPWWWW-NH2 (RRP9W4N), was covalently attached to amphiphilic and ordered mesoporous Pluronic F127 hydrogels made of cross-linked lyotropic liquid crystals through 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide (EDC) and N -hydroxysuccinimide (NHS) chemistry. The AMP-hydrogels showed high antibacterial activity against Staphylococcus epidermidis, Staphylococcus aureus , Pseudomonas aeruginosa , methicillin-resistant S. aureus (MRSA), and multidrug-resistant Escherichia coli for up to 24 h. Furthermore, the AMP-hydrogels did not present any toxicity to human fibroblasts. The AMPs retained their antimicrobial activity up to 48 h in human blood serum, which is a significant increase in stability compared to when used in dissolved state. A pilot in vivo rat model showed 10–100× less viable counts of S. aureus on AMP-hydrogels compared with control hydrogels during the first 3 days of infection. Studies performed on human whole blood showed that blood coagulated more readily in the presence of AMP-hydrogels as compared to hydrogels without AMPs, indicating potential hemostatic activity. Overall, the results suggest that the combination of amphiphilic hydrogels with covalently bonded AMPs has potential to be used as antibacterial wound dressing material to reduce infections and promote hemostatic activity as an alternative to antibiotics or other antimicrobial agents, whose use should be restricted.

Synthetic dry elastomers are randomly cross-linked polymeric networks with isotropic and unordered higher-level structural features. However, their growing use as soft-tissue biomaterials has demanded the need for an ordered and anisotropic nano-micro (or) mesoarchitecture, which is crucial for imparting specific properties such as hierarchical toughening, anisotropic mechanics, sustained drug delivery, and directed tissue growth. High processing cost, poor control in 3D, and compromised mechanical properties have made it difficult to synthesize tough and dry macroscopic elastomers with well-organized nano-microstructures. Inspired from biological design principles, we report a tough ordered mesoporous elastomer formed via bottom-up lyotropic self-assembly of noncytotoxic, polymerizable amphiphilic triblock copolymers and hydrophobic polymers. The elastomer is cross-linked using covalent cross-links and physical hydrophobic entanglements that are organized in a periodic manner at the nanoscale. This transforms into a well-ordered hexagonal arrangement of nanofibrils that are highly oriented at the micron scale, further organized as 3D macroscale objects. The ordered nano-microstructure and molecular multinetwork endows the elastomer with hierarchical toughening while possessing excellent stiffness and elongation comparable to engineering elastomers like silicone and vulcanized rubber. Processing of the elastomer is performed at ambient conditions using 3D printing and photo-cross-linking, which is fast and energy efficient and enables production of complex 3D objects with tailorable sub-millimeter features such as macroporosity. Furthermore, the periodic and amphiphilic nanostructure permits functionalization of the elastomer with secondary components such as inorganic nanoparticles or drug molecules, enabling complementary mechanical properties such as high stiffness and functional capabilities such as in localized drug delivery applications.

No abstract

A material with the ability to rapidly eradicate bacteria via a contact-killing mechanism has the benefit of a more localised treatment that is easy to implement when needed to prevent or treat a bacterial infection. Here, we present an antimicrobial material based on covalently attached antimicrobial peptides (AMPs) to a soft amphiphilic hydrogel. This results in a material that exhibits an antimicrobial effect based on contact-killing. In this study, the antimicrobial efficacy of the AMP-hydrogel was investigated by observing the changes in total bioburden on the intact skin of healthy human volunteers when the AMP-hydrogel dressing was placed on the forearm for three hours. The AMP-hydrogel significantly reduced the bioburden on the skin from a mean value of 1200CFU/cm2 for the untreated skin to 23CFU/cm2. Biocompatibility evaluations of the AMP-hydrogel showed no sign of cytotoxicity, acute systemic toxicity, irritation or sensitisation, demonstrating the safety of the AMP-hydrogel as a potential wound dressing. Leachability studies confirmed no release of AMPs and that the antimicrobial effect was localised to the surface of the hydrogels, demonstrating a pure contact-killing mode of action.