Engineering hydrogels with homogeneous mechanical properties for controlling stem cell lineage specification.

The extracellular matrix (ECM) is mechanically inhomogeneous due to the presence of a wide spectrum of biomacromolecules and hierarchically assembled structures at the nanoscale. Mechanical inhomogeneity can be even more pronounced under pathological conditions due to injury, fibrogenesis, or tumorigenesis. Although considerable progress has been devoted to engineering synthetic hydrogels to mimic the ECM, the effect of the mechanical inhomogeneity of hydrogels has been widely overlooked. Here, we develop a method based on host-guest chemistry to control the homogeneity of maleimide-thiol cross-linked poly(ethylene glycol) hydrogels. We show that mechanical homogeneity plays an important role in controlling the differentiation or stemness maintenance of human embryonic stem cells. Inhomogeneous hydrogels disrupt actin assembly and lead to reduced YAP activation levels, while homogeneous hydrogels promote mechanotransduction. Thus, the method we developed to minimize the mechanical inhomogeneity of hydrogels may have broad applications in cell culture and tissue engineering.

Mediation Mendelian randomisation study on the effects of shift work on coronary heart disease and traditional risk factors via gut microbiota.

Background: Epidemiological evidence suggests that there is an increased risk of coronary heart disease (CHD) related to jobs involving shift work (JSW), but the causality of and mechanism underlying such a relationship remain unclear. Therefore, we aimed to explore the relationship between JSW and CHD, investigating both causality and potential mediating factors. Methods: We performed univariate, multivariate, and mediation Mendelian randomisation (MR) analyses using data from large genome-wide association studies focussed on JSW and CHD, as well as data on some CHD risk factors (type 2 diabetes, hypertension, obesity, and lipids measurement) and 196 gut microbiota taxa. Single-nucleotide polymorphisms significantly associated with JSW acted as instrument variables. We used inverse-variance weighting as the primary method of analysis. Results: Bidirectional MR analysis indicated a robust effect of JSW on increased CHD risk; however, the existence of CHD did not affect the choice of JSW. We identified a mediating effects of type 2 diabetes and hypertension in this relationship, accounting for 11.89% and 14.80% of the total effect of JSW on CHD, respectively. JSW were also causally associated with the risk of type 2 diabetes and hypertension and had an effect on nine microbial taxa. The mediating influence of the Eubacterium brachy group at the genus level explained 16.64% of the total effect of JSW on hypertension. We found limited evidence for the causal effect of JSW on obesity and lipids measurements. Conclusions: Our findings suggest a causal effect of JSW on CHD, diabetes, and hypertension. We also found evidence for a significant connection between JSW and alterations in the gut microbiota. Considering that certain microbial taxa mediated the effect of JSW on hypertension risk, targeting gut microbiota through therapeutics could potentially mitigate high risks of hypertension and CHD associated with JSW.

Dynamic Covalent Hydrogels: Strong yet Dynamic.

Hydrogels are crosslinked polymer networks with time-dependent mechanical response. The overall mechanical properties are correlated with the dynamics of the crosslinks. Generally, hydrogels crosslinked by permanent chemical crosslinks are strong but static, while hydrogels crosslinked by physical interactions are weak but dynamic. It is highly desirable to create synthetic hydrogels that possess strong mechanical stability yet remain dynamic for various applications, such as drug delivery cargos, tissue engineering scaffolds, and shape-memory materials. Recently, with the introduction of dynamic covalent chemistry, the seemingly conflicting mechanical properties, i.e., stability and dynamics, have been successfully combined in the same hydrogels. Dynamic covalent bonds are mechanically stable yet still capable of exchanging, dissociating, or switching in response to external stimuli, empowering the hydrogels with self-healing properties, injectability and suitability for postprocessing and additive manufacturing. Here in this review, we first summarize the common dynamic covalent bonds used in hydrogel networks based on various chemical reaction mechanisms and the mechanical strength of these bonds at the single molecule level. Next, we discuss how dynamic covalent chemistry makes hydrogel materials more dynamic from the materials perspective. Furthermore, we highlight the challenges and future perspectives of dynamic covalent hydrogels.

Correction: Using single molecule force spectroscopy to facilitate a rational design of Ca2+-responsive ß-roll peptide-based hydrogels.

Correction for 'Using single molecule force spectroscopy to facilitate a rational design of Ca2+-responsive ß-roll peptide-based hydrogels' by Lichao Liu et al., J. Mater. Chem. B, 2018, 6, 5303-5312, DOI: 10.1039/C8TB01511B.

Synthesis of chemically crosslinked pullulan/gelatin-based extracellular matrix-mimetic gels.

In order to develop pullulan/gelatin-based gels as potential extracellular matrix-mimetic scaffolds, a "one-step" synthesis method using 1,1'­carbonyldiimidazole (CDI) as activator in DMSO under mild conditions was reported for the first time. Particularly, in contrast to conventional critical requirement of absolute dryness for CDI, it was interesting to find that the formation of gels could be accomplished in the presence of aqueous solvent within a much shorter time, while obtaining improved mechanical properties as demonstrated by compressive tests. UV-Visible spectroscopy, NMR spectrum, TEM and SEM analysis have been employed to evaluate the underlying reaction mechanisms. This method implied that absolute dryness might not be necessary for using CDI as activator in certain cases. This method also represents a new rapid and efficient approach for synthesizing a great variety of chemically crosslinked polysaccharide/protein-based gels as promising material platform potential for tissue engineering and drug delivery applications.

Design of Self-Healing and Electrically Conductive Silk Fibroin-Based Hydrogels.

Self-healing and electrically conductive silk fibroin (SF)-based hydrogels were developed based on the dynamic assembly/disassembly nature of supramolecular complexes and the conductive nature of polypyrrole (PPy). The self-healing properties of the hydrogels were achieved through host-guest interactions between ß-cyclodextrin and amino acid side chains (tyrosine, tryptophan, phenylalanine, and histidine) on SF. PPy deposition was achieved via in situ polymerization of pyrrole using ammonium persulfate as an oxidant and laccase as a catalyst. The PPy-coated hydrogels behaved as an elastomer and displayed excellent electrical properties, with adjustable electrical conductivities ranging from 0.8 ± 0.2 to (1.0 ± 0.3) × 10-3 S·cm-1. Furthermore, possibility of potential utilization of the hydrogels in electrochemistry applications as flexible yet self-healable electrode materials was explored. This study not only shows great potential in expanding the role of silk-based devices for various applications but also provides a useful approach for designing multifunctional self-healing protein-based hydrogels.

Using single molecule force spectroscopy to facilitate a rational design of Ca2+-responsive ß-roll peptide-based hydrogels.

This study demonstrated that incorporation of Ca2+-responsive ß-roll peptides arising from repeat-in-toxin (RTX) into elastomeric proteins provided an approach to construct hydrogels that exhibit Ca2+-responsive mechanical properties through a force analysis-based approach. Use of circular dichroism spectroscopy confirmed that there was a Ca2+-induced conformational change of RTX-based recombinant polyproteins. The polyproteins could be crosslinked into solid hydrogels. Shrinking/swelling measurements showed a Ca2+-responsive dimensional change of the RTX-based hydrogels. Mechanical measurements at constant pulling speed and at constant extension suggested that the mechanical properties of the RTX-based hydrogels were Ca2+-responsive. Experimental single molecule force spectroscopies were used to investigate the nano-mechanical stability of the RTX domains. Single molecule atomic force microscopy and optical tweezers provided evidence that the Ca2+-dependent refolding of the intrinsically disordered RTX led to the force increase. The results indicated that the unique Ca2+-responsive mechanical properties of the RTX-based hydrogels at the macroscopic level could be attributed to the nano-mechanical properties of the RTX domains engineered into individual polyproteins at the single molecule level.