Poly(ɛ-caprolactone) and Eudragit E blends modulate the drug release profiles from FDM printlets.

Thermoplastic polymers have been used to produce filaments by hot melt extrusion (HME), which can be applied to obtain 3D printlets by fused deposition modelling (FDM). Poly(ε-caprolactone) (PCL) is a low melting point thermoplastic polymer that provides HME filaments with excellent mechanical and printability properties. However, due to the highly hydrophobic properties of PCL, they afford printlets with slow drug release behaviour. We hypothesized that blending a less hydrophobic polymer, the Eudragit E (EudE), with PCL could be an approach to increase the drug release rate from PCL 3D printlets. PCL and EudE were blended at different proportions, 50:50, 60:40, 70:30, and 80:20 (w/w), to produce HME filaments. They were produced with dexamethasone at 5 % (w/w) and were effectively extruded and printable by FDM, except that composed of 50:50 (w/w). Printlets had homogeneous distribution of their components. Their drug release behaviour was dependent on the ratio of the polymeric blends. The highest EudE ratio (60:40 w/w) afforded printlets showing the highest release rate. Therefore, adding up to 40 % (w/w) of EudE to PCL does not impair the mechanical and printability properties of its HME filaments. This innovative approach is proposed here to modulate the drug release behaviour from PCL printlets.

Bacteriophage-loaded functional nanofibers for treatment of P. aeruginosa and S. aureus wound infections.

The increasing incidence of infected skin wounds poses a major challenge in clinical practice, especially when conventional antibiotic therapy fails. In this context, bacteriophages emerged as promising alternatives for the treatment of antibiotic-resistant bacteria. However, clinical implementation remains hampered by the lack of efficient delivery approaches to infected wound tissue. In this study, bacteriophage-loaded electrospun fiber mats were successfully developed as next-generation wound dressings for the treatment of infected wounds. We employed a coaxial electrospinning approach, creating fibers with a protective polymer shell, enveloping bacteriophages in the core while maintaining their antimicrobial activity. The novel fibers exhibited a reproducible fiber diameter range and morphology, while the mechanical fiber properties were ideal for application onto wounds. Further, immediate release kinetics for the phages were confirmed as well as the biocompatibility of the fibers with human skin cells. Antimicrobial activity was demonstrated against Staphylococcus aureus and Pseudomonas aeruginosa and the core/shell formulation maintained the bacteriophage activity for 4 weeks when stored at - 20 °C. Based on these promising characteristics, our approach holds great potential as a platform technology for the encapsulation of bioactive bacteriophages to enable the translation of phage therapy into clinical application.

Unraveling an Alternative Mechanism in Polymer Self-Assemblies: An Order-Order Transition with Unusual Molecular Interactions between Hydrophilic and Hydrophobic Polymer Blocks.

Polymer self-assembly leading to cooling-induced hydrogel formation is relatively rare for synthetic polymers and typically relies on H-bonding between repeat units. Here, we describe a non-H-bonding mechanism for a cooling-induced reversible order-order (sphere-to-worm) transition and related thermogelation of solutions of polymer self-assemblies. A multitude of complementary analytical tools allowed us to reveal that a significant fraction of the hydrophobic and hydrophilic repeat units of the underlying block copolymer is in close proximity in the gel state. This unusual interaction between hydrophilic and hydrophobic blocks reduces the mobility of the hydrophilic block significantly by condensing the hydrophilic block onto the hydrophobic micelle core, thereby affecting the micelle packing parameter. This triggers the order-order transition from well-defined spherical micelles to long worm-like micelles, which ultimately results in the inverse thermogelation. Molecular dynamics modeling indicates that this unexpected condensation of the hydrophilic corona onto the hydrophobic core is due to particular interactions between amide groups in the hydrophilic repeat units and phenyl rings in the hydrophobic ones. Consequently, changes in the structure of the hydrophilic blocks affecting the strength of the interaction could be used to control macromolecular self-assembly, thus allowing for the tuning of gel characteristics such as strength, persistence, and gelation kinetics. We believe that this mechanism might be a relevant interaction pattern for other polymeric materials as well as their interaction in and with biological environments. For example, controlling the gel characteristics could be considered important for applications in drug delivery or biofabrication.

Electrospun fibers loaded with antimicrobial peptides for treatment of wound infections.

The widespread resistance of clinically relevant bacteria against established antibiotics emphasizes the urgent need for novel therapeutics. In this context, wound infections constitute a specific challenge, as most systemically applied antibiotics are insufficiently available at the site of infection. Therefore, the local treatment of infected wounds poses a particular challenge regarding the appropriate release kinetics of actives and their residence time in the wound bed. Consequently, design and development of novel, drug-loaded wound dressings constitute a major research focus for the effective treatment of wound infections. In this study, we employed electrospinning to design drug-loaded wound dressings, incorporating the therapeutically promising antimicrobial peptide tyrothricin. By parallel electrospinning, we combined different ratios of water-soluble polyvinylpyrrolidone and water-insoluble methacrylate copolymer (EudragitE), in order to take advantage of their specific mechanical stability and dissolution properties. We fabricated fiber mats constituting mechanically stable wound dressings with a controlled drug release profile, combining an initial burst release above the minimal inhibitory concentration of known wound pathogens and a subsequent prolonged antimicrobial effect of the active ingredient. Antimicrobial activity against Staphylococcusaureus and Staphylococcusepidermidis was successfully proven, thereby introducing our tyrothricin-loaded fiber mats as a promising prospective therapy against typical wound-associated pathogens.

An initiator- and catalyst-free hydrogel coating process for 3D printed medical-grade poly(ε-caprolactone).

Additive manufacturing or 3D printing as an umbrella term for various materials processing methods has distinct advantages over many other processing methods, including the ability to generate highly complex shapes and designs. However, the performance of any produced part not only depends on the material used and its shape, but is also critically dependent on its surface properties. Important features, such as wetting or fouling, critically depend mainly on the immediate surface energy. To gain control over the surface chemistry post-processing modifications are generally necessary, since it's not a feature of additive manufacturing. Here, we report on the use of initiator and catalyst-free photografting and photopolymerization for the hydrophilic modification of microfiber scaffolds obtained from hydrophobic medical-grade poly(ε-caprolactone) via melt-electrowriting. Contact angle measurements and Raman spectroscopy confirms the formation of a more hydrophilic coating of poly(2-hydroxyethyl methacrylate). Apart from surface modification, we also observe bulk polymerization, which is expected for this method, and currently limits the controllability of this procedure.