Despite considerable research and development efforts, the problem of infections related to biomedical devices and implants persists. Bacteria evidently can readily colonize surfaces of synthetic materials, such as those used for the fabrication of catheters, hip and knee implants, and many other devices. As the growing colony encapsulates itself with a protective exocellular bacterial polysaccharide layer, the biofilm becomes much harder to combat than circulating bacteria. Thus, there is a strong need to mitigate bacterial colonization by equipping the surfaces of biomedical devices and implants with features such as surface chemistry and surface roughness that are unfavorable for bacterial attachment. Here we review a number of strategies used for the design of antibacterial coatings. We also discuss specific issues that arise from using various types of coatings.
Tethered lipid bilayers (tBLMs) were obtained by the fusion of liposomes from diphytanoylphosphatidylcholine (DPhyPC) with self-assembled monolayers (SAMs) of a newly designed archaea analogue thiolipid, 2,3-di-O-phytanyl-sn-glycerol-1-tetraethylene glycol-d,l-α-lipoic acid ester (DPTL) on template stripped gold (TSG) films from silicon wafer as a template. SAMs, as characterized by reflection absorption infrared spectroscopy (RAIRS), show a mixture of different conformations of the tetraethylene segment in air, which appears to rearrange into the fully extended conformation when the SAM is immersed into an aqueous electrolyte solution, as deduced from thickness measurements by surface plasmon resonance spectroscopy (SPR). The fusion of liposomes was followed by SPR, quartz crystal microbalance (QCM), and fluorescence microscopy. Highly resistive tBLMs were obtained, as demonstrated by electrochemical impedance spectroscopy (EIS) results, which are equivalent to those for the BLM. This large resistivity is attributed to the ultraflat surface of TSG, as well as to the distinctive architecture of the newly designed molecule. The roughness of the TSG obtained from mica and silicon wafer as template was determined by AFM and compared to that of a Au(111) surface on mica. The largest roughness features of TSG are shown to be 0.5−1 nm, which is small compared to the vertical dimension of the DPTL molecules. This is regarded to be crucial for the self-assembly process, particularly in the case of amphiphilic molecules.
We have synthesized a series of copolymers containing both positively charged (amine, guanidine) and hydrophobic side chains (amphiphilic antimicrobial peptide mimics). To investigate the structure-activity relationships of these polymers, low polydispersity polymethacrylates of varying but uniform molecular weight and composition were synthesized, using a reversible addition-fragmentation chain transfer (RAFT) approach. In a facile second reaction, pendant amine groups were converted to guanidines, allowing for direct comparison of cation structure on activity and toxicity. The guanidine copolymers were much more active against Staphylococcus epidermidis and Candida albicans compared to the amine analogues. Activity against Staphylococcus epidermidis in the presence of fetal bovine serum was only maintained for guanidine copolymers. Selectivity for bacterial over mammalian cells was assessed using hemolytic and hemagglutination toxicity assays. Guanidine copolymers of low to moderate molecular weight and hydrophobicity had high antimicrobial activity with low toxicity. Optimum properties appear to be a balance between charge density, hydrophobic character, and polymer chain length. In conclusion, a suite of guanidine copolymers has been identified that represent a new class of antimicrobial polymers with high potency and low toxicity.
Osteoimmunomodulation has informed the importance of modulating a favorable osteoimmune environment for successful materials-mediated bone regeneration. Nanotopography is regarded as a valuable strategy for developing advanced bone materials, due to its positive effects on enhancing osteogenic differentiation. In addition to this direct effect on osteoblastic lineage cells, nanotopography also plays a vital role in regulating immune responses, which makes it possible to utilize its immunomodulatory properties to create a favorable osteoimmune environment. Therefore, the aim of this study was to advance the applications of nanotopography with respect to its osteoimmunomodulatory properties, aiming to shed further light on this field. We found that tuning the surface chemistry (amine or acrylic acid) and scale of the nanotopography (16, 38, and 68 nm) significantly modulated the osteoimmune environment, including changes in the expression of inflammatory cytokines, osteoclastic activities, and osteogenic, angiogenic, and fibrogenic factors. The generated osteoimmune environment significantly affected the osteogenic differentiation of bone marrow stromal cells, with carboxyl acid-tailored 68 nm surface nanotopography offering the most promising outcome. This study demonstrated that the osteoimmunomodulation could be manipulated via tuning the chemistry and nanotopography, which implied a valuable strategy to apply a "nanoengineered surface" for the development of advanced bone biomaterials with favorable osteoimmunomodulatory properties.
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