Bacterial-infections are mostly due to bacteria in their biofilm-mode of growth. Nanotechnology-based antimicrobials possess excellent potential in biofilm-infection control, overcoming the biological barriers of biofilms.
Biofilms cause persistent bacterial infections and are extremely recalcitrant to antimicrobials, due in part to reduced penetration of antimicrobials into biofilms that allows bacteria residing in the depth of a biofilm to survive antimicrobial treatment. Here, we describe the preparation of surface-adaptive, Triclosan-loaded micellar nanocarriers showing (1) enhanced biofilm penetration and accumulation, (2) electrostatic targeting at acidic pH toward negatively charged bacterial cell surfaces in a biofilm, and (3) antimicrobial release due to degradation of the micelle core by bacterial lipases. First, it was established that mixed-shell-polymeric-micelles (MSPM) consisting of a hydrophilic poly(ethylene glycol) (PEG)-shell and pH-responsive poly(β-amino ester) become positively charged at pH 5.0, while being negatively charged at physiological pH. This is opposite to single-shell-polymeric-micelles (SSPM) possessing only a PEG-shell and remaining negatively charged at pH 5.0. The stealth properties of the PEG-shell combined with its surface-adaptive charge allow MSPMs to penetrate and accumulate in staphylococcal biofilms, as demonstrated for fluorescent Nile red loaded micelles using confocal-laser-scanning-microscopy. SSPMs, not adapting a positive charge at pH 5.0, could not be demonstrated to penetrate and accumulate in a biofilm. Once micellar nanocarriers are bound to a staphylococcal cell surface, bacterial enzymes degrade the MSPM core to release its antimicrobial content and kill bacteria over the depth of a biofilm. This constitutes a highly effective pathway to control blood-accessible staphylococcal biofilms using antimicrobials, bypassing biofilm recalcitrance to antimicrobial penetration.
We summarize different studies describing mechanisms through which bacteria in a biofilm mode of growth resist mechanical and chemical challenges. Acknowledging previous microscopic work describing voids and channels in biofilms that govern a biofilms response to such challenges, we advocate a more quantitative approach that builds on the relation between structure and composition of materials with their viscoelastic properties. Biofilms possess features of both viscoelastic solids and liquids, like skin or blood, and stress relaxation of biofilms has been found to be a corollary of their structure and composition, including the EPS matrix and bacterial interactions. Review of the literature on viscoelastic properties of biofilms in ancient and modern environments as well as of infectious biofilms reveals that the viscoelastic properties of a biofilm relate with antimicrobial penetration in a biofilm. In addition, also the removal of biofilm from surfaces appears governed by the viscoelasticity of a biofilm. Herewith, it is established that the viscoelasticity of biofilms, as a corollary of structure and composition, performs a role in their protection against mechanical and chemical challenges. Pathways are discussed to make biofilms more susceptible to antimicrobials by intervening with their viscoelasticity, as a quantifiable expression of their structure and composition.
Intra-oral scanners will play a central role in digital dentistry in the near future. In this study the accuracy of three intra-oral scanners was compared. Materials and methods: A master model made of stone was fitted with three high precision manufactured PEEK cylinders and scanned with three intra-oral scanners: the CEREC (Sirona), the iTero (Cadent) and the Lava COS (3M). In software the digital files were imported and the distance between the centres of the cylinders and the angulation between the cylinders was assessed. These values were compared to the measurements made on a high accuracy 3D scan of the master model. Results: The distance errors were the smallest and most consistent for the Lava COS. The distance errors for the Cerec were the largest and least consistent. All the angulation errors were small. Conclusions: The Lava COS in combination with a high accuracy scanning protocol resulted in the smallest and most consistent errors of all three scanners tested when considering mean distance errors in full arch impressions both in absolute values and in consistency for both measured distances. For the mean angulation errors, the Lava COS had the smallest errors between cylinders 1–2 and the largest errors between cylinders 1–3, although the absolute difference with the smallest mean value (iTero) was very small (0,0529°). An expected increase in distance and/or angular errors over the length of the arch due to an accumulation of registration errors of the patched 3D surfaces could be observed in this study design, but the effects were statistically not significant.Clinical relevanceFor making impressions of implant cases for digital workflows, the most accurate scanner with the scanning protocol that will ensure the most accurate digital impression should be used. In our study model that was the Lava COS with the high accuracy scanning protocol.
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