Antimicrobial surface coatings that act through a contact-killing mechanism (not diffusive release) could offer many advantages to the design of medical device coatings that prevent microbial colonization and infections. However, as the authors show here, to prevent arriving at an incorrect conclusion about their mechanism of action, it is essential to employ thorough washing protocols validated by surface analytical data. Antimicrobial surface coatings were fabricated by covalently attaching polyene antifungal drugs to surface coatings. Thorough washing (often considered to be sufficient to remove noncovalently attached molecules) was used after immobilization and produced samples that showed a strong antifungal effect, with a log 6 reduction in Candida albicans colony forming units. However, when an additional washing step using surfactants and warmed solutions was used, more firmly adsorbed compounds were eluted from the surface as evidenced by XPS and ToF-SIMS, resulting in reduction and complete elimination of in vitro antifungal activity. Thus, polyene molecules covalently attached to surfaces appear not to have a contact-killing effect, probably because they fail to reach their membrane target. Without additional stringent washing and surface analysis, the initial favorable antimicrobial testing results could have been misinterpreted as evidencing activity of covalently grafted polyenes, while in reality activity arose from desorbing physisorbed molecules. To avoid unintentional confirmation bias, they suggest that binding and washing protocols be analytically verified by qualitative/quantitative instrumental methods, rather than relying on false assumptions of the rigors of washing/soaking protocols.
The adsorption of biomolecules on biomaterial surfaces can promote their integration with surrounding tissue without changing their bulk properties. For biomaterials in bone reconstruction, the promotion of osteogenic differentiation and reduction of inflammation are desirable. Fibrillar coatings are interesting because of fibrils’ high surface area-volume ratio, aiding adsorption and adhesion. Fibrils also serve as a matrix for the immobilization of biomolecules with biological activity, such as the phenolic compound phloroglucinol (PG), the subunit of marine polyphenols. The aim of this work was to investigate the influence of PG coatings on fibroblast- and osteoblast-like cells to increase the osseointegration of titanium implants. Collagen fibril coatings, containing PG at low and high concentrations, were produced on titanium alloy (Ti6Al4V) scaffolds generated by additive manufacturing (AM). These coatings, especially PG-enriched coatings, reduced hydrophobicity and modulated the behavior of human osteosarcoma SaOS-2 and mouse embryonic fibroblast 3T3 cell lines. Both osteoblastic and fibroblastic cells spread and adhered well on PG-enriched coatings. Coatings significantly reduced the inflammatory response. Moreover, osteogenic differentiation was promoted by collagen coatings with a high PG concentration. Thus, the enrichment of collagen fibril coatings with PG is a promising strategy to improve Ti6Al4V implants for bone contact in orthopedics and dentistry and is worthy of further investigation.
There are many reports of antimicrobial coatings bearing immobilized active agents on surfaces; however, strong analytical evidence is required to verify that the agents are indeed covalently attached to the surface. In the absence of such evidence, antimicrobial activity could result from a release of active agents. We report a detailed assessment of antifungal surface coatings prepared using covalent attachment chemistries, with the aim of establishing a set of instrumental and biological evidence required to convincingly demonstrate antimicrobial activity due to nonreleasing, surface active compounds and to exclude the alternate possibility of activity due to release. The strongest biological evidence initially supporting permanent antifungal activity was the demonstration of the ability to reuse samples in multiple, sequential pathogen challenges. However, additional supporting evidence from washing studies and instrumental analysis is also required to probe the possibility of gradual desorption of strongly physisorbed compounds versus covalently attached compounds. Potent antifungal surface coatings were prepared from approved pharmaceutical compounds from the echinocandin drug class (caspofungin, anidulafungin, and micafungin) and assessed by microbiological tests and instrumental methods. Carbonyl diimidazole linking chemistry enabled covalent attachment of caspofungin, anidulafungin, and micafungin to plasma polymer surfaces, with antifungal surface activity likely caused by molecular orientations that present the lipophilic tail toward interfacing fungal cells. This study demonstrates the instrumental and biological evidence required to convincingly ascertain activity due to nonreleasing, surface active compounds and summarize these as three criteria for assessing other reports on surface-immobilized antimicrobial compounds.
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