Anhydrous polymer-based coating with sustainable controlled release functionality for facile, efficacious impregnation, and delivery of antimicrobial peptides.

Anhydrous polymers are actively explored as alternative materials to overcome limitations of conventional hydrogel-based antibacterial coating. However, the requirement for strong organic solvent in polymerization reactions often necessitates extra protection steps for encapsulation of target biomolecules, lowering encapsulation efficiency, and increasing process complexity. This study reports a novel coating strategy that allows direct solvation and encapsulation of antimicrobial peptides (HHC36) into anhydrous polycaprolactone (PCL) polymer-based dual layer coating. A thin 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) film is layered onto the peptide-impregnated PCL as a diffusion barrier, to modulate and enhance release kinetics. The impregnated peptides are eventually released in a controlled fashion. The use of 2,2,2-trifluoroethanol (TFE), as polymerization and solvation medium, induces the impregnated peptides to adopt highly stable turned conformation, conserving peptide integrity, and functionality during both encapsulation and subsequent release processes. The dual layer coating showed sustained antibacterial functionality, lasting for 14 days. In vivo assessment using an experimental mouse wounding model demonstrated good biocompatibility and significant antimicrobial efficacy of the coating under physiological conditions. The coating was translated onto silicone urinary catheters and showed promising antibacterial efficacy, even outperforming commercial silver-based Dover cather. This anhydrous polymer-based platform holds immense potential as an effective antibacterial coating to prevent clinical device-associated infections. The simplicity of the coating process enhances its industrial viability.

Control Release Coating for Urinary Catheters with Enhanced Released Profile for Sustained Antimicrobial Protection.

Catheter-associated urinary tract infections (CAUTIs) are common and pose significant costs to healthcare systems. To date, this problem is largely unsolved as commercially available antimicrobial catheters are still lacking in functionality and performance. A prior study by Lim et al. ( Biotechnol. Bioeng. 2018, 115 (8), 2000-2012) reported the development of a novel anhydrous polycaprolactone (PCL) polymer formulation with controlled-release functionality for antimicrobial peptides. In this follow-up study, we developed an improved antimicrobial peptide (AMP)-impregnated poly(ethylene glycol) (PEG)-polycaprolactone (PCL) anhydrous polymer coating for enhanced sustained controlled-release functionality to provide catheters with effective antimicrobial properties. Varying the ratio of PEG and PEG-PCL copolymers resulted in polymers with different morphologies, consequently affecting the AMP release profiles. The optimal coating, formulated with 10% (w/w) PEG-PCL in PCL, achieved a controlled AMP release rate of 31.65 ± 6.85 µg/mL daily for up to 19 days, with a moderate initial burst release. Such profile is desired for antimicrobial coating as the initial burst release acts as a sterilizer to kill the bacteria present in the urinary tract upon insertion, and the subsequent linear release functions as a prophylaxis to deter opportunistic microbial infections. As a proof-of-concept application, our optimized coating was then applied to a commercial silicone catheter for further antibacterial tests. Preliminary results revealed that our coated catheters outperformed commercial silver-based antimicrobial catheters in terms of antimicrobial performance and sustainability, lasting for 4 days. Application of the controlled-release coating also aids in retarding biofilm formation, showing a lower extent of biofilm formation at the end of seven inoculation cycles.

Simple surface engineering of polydimethylsiloxane with polydopamine for stabilized mesenchymal stem cell adhesion and multipotency.

Polydimethylsiloxane (PDMS) has been extensively exploited to study stem cell physiology in the field of mechanobiology and microfluidic chips due to their transparency, low cost and ease of fabrication. However, its intrinsic high hydrophobicity renders a surface incompatible for prolonged cell adhesion and proliferation. Plasma-treated or protein-coated PDMS shows some improvement but these strategies are often short-lived with either cell aggregates formation or cell sheet dissociation. Recently, chemical functionalization of PDMS surfaces has proved to be able to stabilize long-term culture but the chemicals and procedures involved are not user- and eco-friendly. Herein, we aim to tailor greener and biocompatible PDMS surfaces by developing a one-step bio-inspired polydopamine coating strategy to stabilize long-term bone marrow stromal cell culture on PDMS substrates. Characterization of the polydopamine-coated PDMS surfaces has revealed changes in surface wettability and presence of hydroxyl and secondary amines as compared to uncoated surfaces. These changes in PDMS surface profile contribute to the stability in BMSCs adhesion, proliferation and multipotency. This simple methodology can significantly enhance the biocompatibility of PDMS-based microfluidic devices for long-term cell analysis or mechanobiological studies.

Development of a catheter functionalized by a polydopamine peptide coating with antimicrobial and antibiofilm properties.

Catheter-associated urinary tract infections (CAUTIs) are the most common hospital-acquired infections worldwide, aggravating the problem of antimicrobial resistance and patient morbidity. There is a need for a potent and robust antimicrobial coating for catheters to prevent these infections. An ideal coating agent should possess high antimicrobial efficacy and be easily and economically conjugated to the catheter surface. In this study, we report a simple yet effective immobilization strategy to tether a potent synthetic antimicrobial peptide, CWR11, onto catheter-relevant surfaces. Polydopamine (PD) was deposited as a thin adherent film onto a polydimethylsiloxane (PDMS) surface to facilitate attachment of CWR11 onto the PD-functionalized polymer. Surface characterization of the CWR11-tethered surfaces confirmed the successful immobilization of peptides onto the PD-coated PDMS. The CWR11-immobilized PDMS slides displayed excellent antimicrobial (significant inhibition of 5×10(4) colony-forming units of CAUTI-relevant microbes) and antibiofilm (∼92% enhanced antibacterial adherence) properties. To assess its clinical relevance, the PD-based immobilization platform was translated onto commercial silicone-coated Foley catheters. The CWR11-impregnated catheter displayed potent bactericidal properties against both Gram-positive and Gram-negative bacteria, and retained its antimicrobial functionality for at least 21days, showing negligible cytotoxicity against human erythrocyte and uroepithelial cells. The outcome of this study demonstrates the proof-of-concept potential of a polydopamine-CWR11-functionalized catheter to combat CAUTIs.

Immobilization studies of an engineered arginine-tryptophan-rich peptide on a silicone surface with antimicrobial and antibiofilm activity.

With the rapid rise of antibiotic-resistant-device-associated infections, there has been increasing demand for an antimicrobial biomedical surface. Synthetic antimicrobial peptides that have excellent bactericidal potency and negligible cytotoxicity are promising targets for immobilization on these target surfaces. An engineered arginine-tryptophan-rich peptide (CWR11) was developed, which displayed potent antimicrobial activity against a broad spectrum of microbes via membrane disruption, and possessed excellent salt resistance properties. A tethering platform was subsequently developed to tether CWR11 onto a model polymethylsiloxane (PDMS) surface using a simple and robust strategy. Surface characterization assays such as attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and energy-dispersive X-ray spectroscopy (EDX) confirmed the successful grafting of CWR11 onto the chemically treated PDMS surface. The immobilized peptide concentration was 0.8 ± 0.2 µg/cm(2) as quantitated by sulfosuccinimidyl-4-o-(4,4-dimethoxytrityl) butyrate (sulfo-SDTB) assay. Antimicrobial assay and cytotoxic investigation confirmed that the peptide-immobilized surface has good bactericidal and antibiofilm properties, and is also noncytotoxic to mammalian cells. Tryptophan-arginine-rich antimicrobial peptides have the potential for antimicrobial protection of biomedical surfaces and may have important clinical applications in patients.