Search Results (3)

This study aimed to evaluate the dimensional stability of maxillary diagnostic casts fabricated from a biobased model resin, which consists of 50% renewable raw materials for sustainable production, a model resin, and stone, over one month. A master maxillary stone cast was digitized with a laboratory scanner to generate a reference file. This master cast was also scanned with an intraoral scanner to additively manufacture casts with a biobased model resin (BAM) and a model resin (AM). Polyvinylsiloxane impressions of the master cast were also made and poured in type III stone (CV) (n = 8). The same laboratory scanner was used to digitize each model one day (T0), 1 week (T1), 2 weeks (T2), 3 weeks (T3), and 4 weeks (T4) after fabrication. Deviations from the reference file were calculated with an analysis software and analyzed with generalized linear model analysis (α = 0.05). The interaction between the material and the time point affected measured deviations (p < 0.001). Regardless of the time point, CV had the lowest and AM had the highest deviations (p < 0.001). BAM mostly had lower deviations at T0 and mostly had higher deviations at T4 (p ≤ 0.011). AM had the highest deviations at T4 and then at T3, whereas it had the lowest deviations at T0 (p ≤ 0.002). The measured deviations of CV increased after each time point (p < 0.001). BAM casts had deviations within the previously reported clinically acceptable thresholds over one month and had acceptable dimensional stability. Therefore, tested biobased resin may be a viable alternative for the sustainable manufacturing of maxillary diagnostic casts that are to be used clinically. Full article

Lipid nanoparticles (LNPs) have gained great attention as carriers for mRNA-based therapeutics, finding applications in various indications, extending beyond their recent use in vaccines for infectious diseases. However, many aspects of LNP structure and their effects on efficacy are not well characterized. To further exploit the potential of mRNA therapeutics, better control of the relationship between LNP formulation composition with internal structure and transfection efficiency in vitro is necessary. We compared two well-established ionizable lipids, namely DODMA and MC3, in combination with two helper lipids, DOPE and DOPC, and two polymer-grafted lipids, either with polysarcosine (pSar) or polyethylene glycol (PEG). In addition to standard physicochemical characterization (size, zeta potential, RNA accessibility), small-angle X-ray scattering (SAXS) was used to analyze the structure of the LNPs. To assess biological activity, we performed transfection and cell-binding assays in human peripheral blood mononuclear cells (hPBMCs) using Thy1.1 reporter mRNA and Cy5-labeled mRNA, respectively. With the SAXS measurements, we were able to clearly reveal the effects of substituting the ionizable and helper lipid on the internal structure of the LNPs. In contrast, pSar as stealth moieties affected the LNPs in a different manner, by changing the surface morphology towards higher roughness. pSar LNPs were generally more active, where the highest transfection efficiency was achieved with the LNP formulation composition of MC3/DOPE/pSar. Our study highlights the utility of pSar for improved mRNA LNP products and the importance of pSar as a novel stealth moiety enhancing efficiency in future LNP formulation development. SAXS can provide valuable information for the rational development of such novel formulations by elucidating structural features in different LNP compositions. Full article

mRNA vaccines are finally ready to assume their rightful place at the forefront of nucleic acid-based vaccines. Major achievements within the last two decades have turned this highly versatile molecule into a safe and very attractive pharmaceutical platform that combines many positive attributes able to address a broad range of diseases, including cancer. The simplicity of mRNA vaccines greatly reduces complications generally associated with the production of biological vaccines. Intrinsic costimulatory and inflammatory triggers in addition to the provision of the antigenic information makes mRNA an all-in-one molecule that does not need additional adjuvants and that does not pose the risk of genomic integration. Clinical studies in various cancer types are moving forward and promising results with favorable clinical outcome are awaited. This review will recapitulate conceptual, mechanistic and immune-related features of this highly versatile molecule, elucidate how these features have been addressed in the past, and how comprehensive understanding can foster further optimization for broad application possibilities in cancer treatment. Full article