The use of antimicrobial materials, for example, silver nanoparticles, has been a cause for concern because they often exert an adverse effect on environmental and safety during their preparation and use. In this study, we report a class of green antimicrobial coating based on a supramolecular assembly of a protein extracted from daily food, without the addition of any other hazardous agents. It is found that a self-assembled nanofilm by mere hen egg white lysozyme has durable in vitro and in vivo broad-spectrum antimicrobial efficacy against Gram-positive/negative and fungi. Such enhanced antimicrobial capability over native lysozyme is attributed to a synergistic combination of positive charge and hydrophobic amino acid residues enriched on polymeric aggregates in the lysozyme nanofilm. Accompanied with high antimicrobial activity, this protein-based PTL material simultaneously exhibits the integration of multiple functions including antifouling, antibiofilm, blood compatibility, and low cytotoxicity due to the existence of surface hydration effect. Moreover, the bioinspired adhesion mediated by the amyloid structure contained in the nanofilm induces robust transfer and self-adhesion of the material onto virtually arbitrary substrates by a simple one-step aqueous coating or solvent-free printing in 1 min, thereby allowing an ultrafast route into practical implications for surface-functionalized commodity and biomedical devices. Our results demonstrate that the application of pure proteinaceous substance may afford a cost-effective green biomaterial that has high antimicrobial activity and low environmental impact.

In recent years, microbial colonization on the surface of biomedical implants/devices has become a severe threat to human health. Herein, surface-immobilized guanidine derivative block copolymers create an antimicrobial and antifouling dual-functional coating. We report the preparation of an antimicrobial and antifouling block copolymer by the conjugation of polyhexanide (PHMB) with either allyl glycidyl ether or allyloxy polyethylene glycol (APEG; MW 1200 and 2400). The allyl glycidyl ether modified PHMB (A-PHMB) and allyloxy polyethylene glycol modified PHMB (APEG-PHMB) copolymers were grafted onto a silicone rubber surface as a bottlebrush-like coating, respectively, using a plasma-UV-assisted surface-initiated polymerization. Both A-PHMB and APEG-PHMB coatings exhibited excellent broad-spectrum antimicrobial properties against Gram-negative/positive bacteria and fungi. The APEG-PHMB coating displayed an improved antibiofilm as well as antifouling properties and a long reusable cycle, compared with two other coatings, due to its abundant PEG blocks among those copolymers. Also, the APEG-PHMB-coated silicone coupons were biocompatible toward mammalian cells, as revealed by in vitro hemocompatibile and cytotoxic assays. An in vivo study showed a significant decline of Escherichia coli colonies with a 5-log reduction, indicating the APEG-PHMB coating surface worked effectively in the rodent subcutaneous infection model. This PHMB-based block copolymer coating is believed to be an effective strategy to prevent biomaterial-associated infections.

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Biofilms in chronic wounds, including diabetic foot ulcers, pressure ulcers, and venous leg ulcers, pose a major challenge to wound management. Herein, we report a Janus-type antimicrobial dressing for eradication of biofilms in chronic wounds. The dressing consists of electrospun nanofiber membranes coupled with dissolvable microneedle arrays to enable effective delivery of a database designed antimicrobial peptide to both inside and outside biofilms. This antimicrobial dressing exhibited high efficacy against a broad spectrum of resistant pathogens in vitro. Importantly, such a dressing was able to eradicate methicillin-resistant Staphylococcus aureus (MRSA) biofilms in both an ex vivo human skin wound infection model and a type II diabetic mouse wound infection model after daily treatment without applying surgical debridement. Most *

Biomedical device-associated infections which engender severe threat to public health require feasible solutions. In this study, block copolymers consisting of antimicrobial, antifouling, and surface-tethering segments in one molecule are synthesized and grafted on polymeric substrates by a facile plasma/autoclave-assisted method. Hetero-bifunctional polyethylene glycol (PEG) with allyl and tosyl groups (APEG-OTs) is first prepared. PEGs with different molecular weights (1200 and 2400 Da) are employed. Polyhexamethylene guanidine (PHMG) which has excellent broad-spectrum antimicrobial activity and thermal/chemical stability, is conjugated with APEG-OTs to generate the block copolymer (APEG-PHMG). Allyl terminated PHMG (A-PHMG) without PEG segments is also synthesized by reacting PHMG with allyl glycidyl ether. The synthesized copolymers are thermal initiated by autoclaving and grafted on plasma pretreated silicone surface, forming permanently bonded bottlebrush-like coatings. Both A-PHMG and APEG -PHMG coatings exhibit potent antimicrobial activity against gram-positive/negative bacteria and fungus, whereas APEG -PHMG coatings show superior antifouling activity and long-term reusability to A-PHMG coating. APEG -PHMG coating demonstrates the most effective in vitro antibiofilm and protein/platelet-resistant properties, as well as excellent hemo/biocompatibility. Furthermore, APEG -PHMG greatly reduces the bacteria number with 5-log reduction in a rodent subcutaneous infection model. This rationally designed dual-functional antimicrobial and antifouling coating has great potential in combating biomedical devices/implant-associated infections.

A series of broad-spectrum antimicrobial cationic peptidopolysaccharides have been synthesized using a facile thiol–ene ‘click’ chemistry.

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from uniaxial alignment at tendons, to moderate alignment at fibrocartilage sites, to random organization at bones. [3] Likewise, in articular cartilage, collagen fibers in the superficial zone are parallel to the articular surface, randomly oriented in the middle zone, and perpendicular to the articular surface in the deep zone. [4] The other type of gradient in biological systems is related to a varying degree to the variations in local concentrations/contents of biominerals, inorganic ions, and biomolecules, and water. Compositional gradients play a critical role in developmental biology, tissue homeostasis, and tissue repair by enabling cells to infer their spatial location and determine their fate accordingly. [5-7] Morphogens acting as graded positional cues control cell fate specification in many developing tissues. [8,9] Tranforming growth factor-beta 1 is secreted from the bone matrix and activated during bone tissue breakdown carried out by osteoclasts, resulting in a gradient that directs migration of bone mesenchymal stem cells (BMSCs) to bone remodeling sites, thereby balancing bone resorption and formation. [10] Transforming the ideas of these naturally occurring gradients into synthetic scaffolds renders tremendous potential to ameliorate their functions for regulating cell responses including distribution, morphology, adhesion (attachment), survival (proliferation), migration, metabolism, and differentiation. [9,11,12] Attempts have been made to fabricate scaffolds with structural (e.g., pore size, fiber organization) and compositional (e.g., minerals, adhesion ligands, growth factors) gradients using 3D printing, microfluidics, contact printing, ultravioletassisted capillary molding, porogen, thermally induced phase separation, deposition, diffusion, etching, buoyancy, and centrifugal force. [2,11-25] However, these methods yield scaffolds that often lack biomimetic nanofibrous architecture, aligned topographic cues, 3D configuration, or high cell seeding efficiency. To maximize the physiological relevance and cell seeding efficiency and direct cell behavior, there is a great need to develop biomimetic 3D scaffolds with incorporation of structural and compositional gradients. We reported, for the first time, the conversion of 2D electrospun poly(ε-caprolactone) (PCL) nanofiber membranes into biomimetic, stem-cell regulating, 3D hierarchical assemblies with structural and compositional gradients. We chose PCL as raw material as it is biodegradable New methods are described for converting 2D electrospun nanofiber membranes to 3D hierarchical assemblies with structural and compositional gradients. Pore-size gradients are generated by tuning the expansion of 2D membranes in different layers with incorporation of various amounts of a surfactant during the gas-foaming process. The gradient in fiber organizations is formed by expanding 2D nanofiber membranes composed of multiple regions collected by varying rotating speeds of mandrel. A compositional gradient on 3D assemblies consisting of radially alig...