A multifunctional micropore-forming bioink with enhanced anti-bacterial and anti-inflammatory properties.

Three-dimensional (3D) bioprinting has emerged as an enabling tool for various biomedical applications, such as tissue regeneration and tissue model engineering. To this end, the development of bioinks with multiple functions plays a crucial role in the applications of 3D bioprinting technologies. In this study, we propose a new bioink based on two immiscible aqueous phases of gelatin methacryloyl (GelMA) and dextran, further endowed with anti-bacterial and anti-inflammatory properties. This micropore-forming GelMA-dextran (PGelDex) bioink exhibited excellent printability with vat-polymerization, extrusion, and handheld bioprinting methods. The porous structure was confirmed after bioprinting, which promoted the spreading of the encapsulated cells, exhibiting the exceptional cytocompatibility of this bioink formulation. To extend the applications of such a micropore-forming bioink, interleukin-4 (IL-4)-loaded silver-coated gold nanorods (AgGNRs) and human mesenchymal stem cells (MSCs) were simultaneously incorporated, to display synergistic anti-infection behavior and immunomodulatory function. The results revealed the anti-bacterial properties of the AgGNR-loaded PGelDex bioink for both Gram-negative and Gram-positive bacteria. The data also indicated that the presence of IL-4 and MSCs facilitated macrophage M2-phenotype differentiation, suggesting the potential anti-inflammatory feature of the bioink. Overall, this unique anti-bacterial and immunomodulatory micropore-forming bioink offers an effective strategy for the inhibition of bacterial-induced infections as well as the ability of immune-regulation, which is a promising candidate for broadened tissue bioprinting applications.

Empirical study of correlated survival times for recurrent events with proportional hazards margins and the effect of correlation and censoring.

BACKGROUND: In longitudinal studies where subjects experience recurrent incidents over a period of time, such as respiratory infections, fever or diarrhea, statistical methods are required to take into account the within-subject correlation. METHODS: For repeated events data with censored failure, the independent increment (AG), marginal (WLW) and conditional (PWP) models are three multiple failure models that generalize Cox's proportional hazard model. In this paper, we revise the efficiency, accuracy and robustness of all three models under simulated scenarios with varying degrees of within-subject correlation, censoring levels, maximum number of possible recurrences and sample size. We also study the methods performance on a real dataset from a cohort study with bronchial obstruction. RESULTS: We find substantial differences between methods and there is not an optimal method. AG and PWP seem to be preferable to WLW for low correlation levels but the situation reverts for high correlations. CONCLUSIONS: All methods are stable in front of censoring, worsen with increasing recurrence levels and share a bias problem which, among other consequences, makes asymptotic normal confidence intervals not fully reliable, although they are well developed theoretically.

Simultaneous marginal survival estimators when doubly censored data is present.

A doubly censoring scheme occurs when the lifetimes T being measured,from a well-known time origin, are exactly observed within a window [L, R] of observational time and are otherwise censored either from above (right-censored observations)or below (left-censored observations). Sample data consists on the pairs (U, δ)where U = min{R, max{T, L}} and δ indicates whether T is exactly observed (δ = 0),right-censored (δ = 1) or left-censored (δ = −1). We are interested in the estimation of the marginal behaviour of the three random variables T, L and R based on the observed pairs (U, δ).We propose new nonparametric simultaneous marginal estimators S(T) , S(L) and S(R) for the survival functions of T, L and R, respectively, by means of an inverse-probability-of-censoring approach. The proposed estimators S(T) , S(L) and S(R) are not computationally intensive, generalize the empirical survival estimator and reduce to the Kaplan-Meier estimator in the absence of left-censored data. Furthermore,S(T) is equivalent to a self-consistent estimator, is uniformly strongly consistent and asymptotically normal. The method is illustrated with data from a cohort of drug users recruited in a detoxification program in Badalona (Spain). For these data we estimate the survival function for the elapsed time from starting IV-drugs to AIDS diagnosis, as well as the potential follow-up time. A simulation study is discussed to assess the performance of the three survival estimators for moderate sample sizes and different censoring levels.

Skew-laplace and cell-size distribution in microbial axenic cultures: statistical assessment and biological interpretation.

We report a skew-Laplace statistical analysis of both flow cytometry scatters and cell size from microbial strains primarily grown in batch cultures, others in chemostat cultures and bacterial aquatic populations. Cytometry scatters best fit the skew-Laplace distribution while cell size as assessed by an electronic particle analyzer exhibited a moderate fitting. Unlike the cultures, the aquatic bacterial communities clearly do not fit to a skew-Laplace distribution. Due to its versatile nature, the skew-Laplace distribution approach offers an easy, efficient, and powerful tool for distribution of frequency analysis in tandem with the flow cytometric cell sorting.

Skew-Laplace distribution in Gram-negative bacterial axenic cultures: new insights into intrinsic cellular heterogeneity.

The application of flow cytometry and skew-Laplace statistical analysis to assess cellular heterogeneity in Gram-negative axenic cultures is reported. In particular, fit to the log-skew-Laplace distribution for cellular side scatter or 'granulosity' is reported, and a number of theoretical and applied issues are considered in relation to the biological significance of this fit.