Healthcare-acquired infections and multi-drug resistance in pathogens pose a major crisis for the healthcare industry. Novel antibiotics which are effective against resistant strains and unlikely to elicit strong resistance are sought after in these settings. We have previously developed synthetic mimics of ubiquitous antimicrobial peptides and have worked to apply a lead compound, CSA-131, to the crisis. We aimed to generate a system of CSA-131-containing coatings for medical devices that can be adjusted to match elution and compound load for various environments and establish their efficacy in preventing the growth of common pathogens in and around these devices. Peripherally inserted central catheter (PICC) lines were selected for our substrate in this work, and a polyurethane-based system was used to establish coatings for evaluation. Microbial challenges by methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans were performed and SEM was used to evaluate coating structure and colonization. The results indicate that selected coatings show activity against selected planktonic pathogens that extend between 16 and 33 days, with similar periods of biofilm prevention.

A new method for producing an antibacterial, bioactive hybrid coating on titanium is developed. Using plasma treatment, a layer containing calcium phosphates is generated. Next, by applying a ceragenin in PLGA, a bioactive coating is created. Coatings morphology promotes cell adhesion. The polymer plays the role of a reinforcing component, increasing the wearproof of the coating. Due to the positive charged ceragenin, the coating has optimal wettability and SFE for cell adhesion. A time-kill kinetic assay against MRSA demonstrates that growth is reduced to the limit of detection in two hours. Daily challenge by MRSA and Escherichia coli demonstrates significant reduction of bacterial growth. RT-qPCR and immunohistochemical analysis confirmed that the coatings have a high anti-inflammatory effect and are capable of effectively reducing overall inflammation. The use of coatings resulted in restoration of the spleen's morphological structure. The resulting coatings are an effective way to modify the surface of implants.

BackgroundImplant-associated infections (IAIs) affect up to 10% of orthopedic patients and remain a leading cause of revision surgery, sepsis, and mortality. Current antimicrobial coatings fail to address the dual challenge of biofilm prevention and endotoxin-driven inflammation.TechnologyWe develop a hierarchical coating combining a plasma electrolytic oxidation (PEO)-derived calcium phosphate layer with a poly(lactic-co-glycolic acid) (PLGA) reservoir encapsulating the cationic steroid antimicrobial ceragenin CSA-131. This hybrid architecture provides sustained CSA-131 release over 14 days, achieving >6-log reduction of methicillin-resistant Staphylococcus aureus (MRSA) within 2 hours and maintaining >3-log suppression against MRSA and Escherichia coli for up to 6 days. The PLGA-reinforced PEO architecture provides 19-fold reduction in wear and 3-fold increase in critical load versus PEO alone, while optimal surface energy (71.6 mJ m–2) promotes cells adhesion.ResultsBeyond direct bactericidal activity, CSA-131 neutralizes lipopolysaccharide (LPS), suppressing LPS-induced expression of pro-inflammatory markers (IL-1β, TNF-α, IL-6, CD68, CD86) by >80% (p<0.001) in RAW264.7 macrophages. In a 60-day murine intermuscular implantation model, CSA-131-coated implants prevented systemic inflammation, restored splenic architecture, and eliminated the splenic hyperplasia and immune activation observed with untreated titanium upon LPS challenge. This ceragenin-based strategy resolves the critical trade-off between antimicrobial efficacy and osseointegration, offering a clinically translatable platform for infection-resistant titanium implants with dual antibacterial and anti-inflammatory functions.