Hydrogel morphogenesis induced by force-controlled growth.

Morphogenesis is one of the most marvelous natural phenomena. The morphological characteristics of biological organs develop through growth, which is often triggered by mechanical force. In this study, we propose a bioinspired strategy for hydrogel morphogenesis through force-controlled chemical reaction and growth under isothermal conditions. We adopted a double network (DN) hydrogel with sacrificial bonds. Applying mechanical force to the gel caused deformation and sacrificial bond rupture. By supplying monomers to the gel, the radicals generated by the bond rupture triggered the formation of a new network inside the deformed gel. This new network conferred plasticity to the elastic gel, allowing it to maintain its deformed shape, along with increased volume and strength. We demonstrated that sheet-shaped DN hydrogels rapidly adopted various three-dimensional shapes at ambient temperature when subjected to forces such as drawing and blowing. This mechanism enables morphogenesis of elastic hydrogels and will promote the application of these materials in biomedical fields and soft machines.

Effect of the Activation Force of Mechanophore on Its Activation Selectivity and Efficiency in Polymer Networks.

In recent decades, more than 100 different mechanophores with a broad range of activation forces have been developed. For various applications of mechanophores in polymer materials, it is crucial to selectively activate the mechanophores with high efficiency, avoiding nonspecific bond scission of the material. In this study, we embedded cyclobutane-based mechanophore cross-linkers (I and II) with varied activation forces (fa) in the first network of the double network hydrogels and quantitively investigated the activation selectivity and efficiency of these mechanophores. Our findings revealed that cross-linker I, with a lower activation force relative to the bonds in the polymer main chain (fa-I/fa-chain = 0.8 nN/3.4 nN), achieved efficient activation with 100% selectivity. Conversely, an increase of the activation force of mechanophore II (fa-II/fa-chain = 2.5 nN/3.4 nN) led to a significant decrease of its activation efficiency, accompanied by a substantial number of nonspecific bond scission events. Furthermore, with the coexistence of two cross-linkers, significantly different activation forces resulted in the almost complete suppression of the higher-force one (i.e., I and III, fa-I/fa-III = 0.8 nN/3.4 nN), while similar activation forces led to simultaneous activations with moderate efficiencies (i.e., I and IV, fa-I/fa-IV = 0.8 nN/1.6 nN). These findings provide insights into the prevention of nonspecific bond rupture during mechanophore activation and enhance our understanding of the damage mechanism within polymer networks when using mechanophores as detectors. Besides, it establishes a principle for combining different mechanophores to design multiple mechanoresponsive functional materials.

Azobenzene as a photoswitchable mechanophore.

Azobenzene has been widely explored as a photoresponsive element in materials science. Although some studies have investigated the force-induced isomerization of azobenzene, the effect of force on the rupture of azobenzene has not been explored. Here we show that the light-induced structural change of azobenzene can also alter its rupture forces, making it an ideal light-responsive mechanophore. Using single-molecule force spectroscopy and ultrasonication, we found that cis and trans para-azobenzene isomers possess contrasting mechanical properties. Dynamic force spectroscopy experiments and quantum-chemical calculations in which azobenzene regioisomers were pulled from different directions revealed that the distinct rupture forces of the two isomers are due to the pulling direction rather than the energetic difference between the two isomers. These mechanical features of azobenzene can be used to rationally control the macroscopic fracture behaviours of polymer networks by photoillumination. The use of light-induced conformational changes to alter the mechanical response of mechanophores provides an attractive way to engineer polymer networks of light-regulatable mechanical properties.

[Retracted] Role of microRNA­210 in human intervertebral disc degeneration.

[This retracts the article DOI: 10.3892/etm.2016.3176.].

Sustainable mechanochemical growth of double-network hydrogels supported by vascular-like perfusion.

Double-network (DN) gels are unique mechanochemical materials owing to their structures that can be dynamically remodelled during use. The mechanical energy applied to DN gels is efficiently transferred to the chemical bonds of the brittle network, generating mechanoradicals that initiate the polymerisation of pre-loaded monomers, thereby remodelling the materials. To attain continuous remodelling or growth in response to repetitive mechanical stimuli, a sustainable supply of chemical reagents to such dynamic materials is essential. In this study, inspired by the vascular perfusion transporting nutrients to cells, we constructed a circulatory system for a continuous supply of chemicals to channel-containing DN hydrogels (c-DN gels). The perfusion of monomer solutions through the channel and permeability of the c-DN gels not only replenishes the monomers consumed by the polymerisation but also replenishes the water loss caused by the surface evaporation of hydrogel, thereby freeing the mechanochemical process of DN gels from the constraints of the underwater environment. The facile chemical supply enabled us to modulate the mechanical enhancement of the c-DN gel and attain muscle-like strengthening under repeated mechanical training in deoxygenated air. We also studied the kinetics of polymer growth and strengthening and deciphered unique features of mechanochemical reaction in DN gels including the extremely long-living radicals and delayed mechanical strengthening.

Exposure to acute waterborne cadmium caused severe damage on lipid metabolism of freshwater fish, revealed by nuclear lipid droplet deposition in hepatocytes of rare minnow.

Cadmium (Cd) is a widely distributed aquatic toxic heavy metal with the potential to disrupt fish metabolism; however, more research is needed to clarify the underlying mechanisms. In the present study, rare minnows (Gobiocypris rarus) were used to detect the effects of cadmium on freshwater fish lipid metabolism and its underlying mechanism by histopathological observation, measurement of serum and liver biochemical indexes, and analysis of gene expression in terms of lipid oxidation, synthesis and transport. Here, severe damage, such as cytoplasmic lipid droplet (LD) accumulation, ectopic deposition of LDs, and the appearance of nuclear LDs (nLDs), was detected after exposure to 2.0 mg/L or higher concentrations (2.5 and 2.8 mg/L CdCl2) for 96 h. Other damage included abnormal increases in rough endoplasmic reticulum (RER) lamellae in a fingerprint or concentric circle pattern and necrosis of hepatocytes, and which was observed in the livers of fish exposed to 2.0 mg/L CdCl2.. Both hepatic and serum lipids, such as triglycerides and total cholesterol, were significantly increased after exposure to 2.0 mg/L CdCl2, as was serum lipase (LPS). Hepatic lipase and lipoprotein lipase remained unchanged, in accordance with the unchanged hepatic mRNA transcripts of PPARɑ. Furthermore, the mRNA transcripts of both SCD and SQLE were significantly decreased. Moreover, hepatic and serum low-density and high-density lipoprotein cholesterol showed significant changes, which were accompanied by a significant increase and decrease in hepatic APOAI and APOB100 mRNA levels, respectively. All the results indicate the presence of severe damage to hepatic lipid metabolism and that disrupted lipid transport may play a key role in the accumulation of hepatic LDs. In addition, the hepatic nLDs of nonmammalian vertebrates and their location across the nuclear envelope are intriguing, suggesting that large-size nLDs are a common marker for severe liver damage.

Mortality of Escalation and Modulation Antithrombotic Therapy in Coronary Artery Disease Patients: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: The net clinical benefit of antithrombotic therapy (ATT) reflects the concomitant effects of bleeding and ischemic events. OBJECTIVES: We sought to assess the overall effect of the modulation or escalation of ATT on all-cause mortality as well as ischemic and bleeding events. METHODS: We performed a meta-analysis of randomized controlled trials comparing escalation or modulation of ATT versus standard ATT in patients with coronary artery disease. A total of 32 studies with 160,659 subjects were enrolled in this analysis. RESULTS: Neither escalation nor modulation of ATT has significant effect on all-cause mortality (escalation: relative risk [RR]: 0.94, 95% confidence interval [CI]: 0.85-1.04; modulation: RR: 0.90; 95% CI: 0.81-1.01). Compared with standard ATT therapy, escalation of ATT was associated with lower risk of myocardial infarction (MI; RR: 0.84, 95% CI: 0.76-0.94), but had a higher risk of major or minor bleeding (RR: 1.38, 95% CI: 1.15-1.66). Modulation of ATT was associated with a similar risk of MI (RR: 1.07, 95% CI: 0.96-1.19), but a reduced risk for major or minor bleeding (RR: 0.58, 95% CI: 0.51-0.66). Meta-regression combining both escalation and modulation studies found that the heterogeneity of all-cause mortality was mainly attributed to the heterogeneity of major or minor bleeding (adjusted R-squared = 100.00%, p = 0.004), but not to MI. CONCLUSION: Either escalation or modulation of ATT has little benefit in all-cause mortality. The variability of the treatment effects on all-cause mortality was mainly attributed to the variability of major or minor bleeding, but not to MI.

Comparative effectiveness of prophylactic strategies for preeclampsia: a network meta-analysis of randomized controlled trials.

OBJECTIVE: Preeclampsia is a common disease during pregnancy that leads to fetal and maternal adverse events. Few head-to-head clinical trials are currently comparing the effectiveness of prophylactic strategies for preeclampsia. In this network meta-analysis, we aimed to compare the efficacy of prophylactic strategies for preventing preeclampsia in pregnant women at risk. DATA SOURCES: Articles published in or before September 2021 from PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, references of key articles, and previous meta-analyses were manually searched. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials comparing prophylactic strategies preventing preeclampsia with each other or with negative controls were included. METHODS: Two reviewers independently extracted data, assessed the risk of bias, and assessed evidence certainty. The efficacy of prophylactic strategies was estimated by frequentist and Bayesian network meta-analysis models. The primary composite outcome was preeclampsia/ pregnancy-induced hypertension. RESULTS: In total, 130 trials with a total of 112,916 patients were included to assess 13 prophylactic strategies. Low-molecular-weight heparin (0.60; 95% confidence interval, 0.42-0.87), vitamin D supplementation (0.65; 95% confidence interval, 0.45-0.95), and exercise (0.68; 95% confidence interval, 0.50-0.92) were as efficacious as calcium supplementation (0.71; 95% confidence interval, 0.62-0.82) and aspirin (0.79; 95% confidence interval, 0.72-0.86) in preventing preeclampsia/pregnancy-induced hypertension, with a P score ranking of 85%, 79%, 76%, 74%, and 61%, respectively. In the head-to-head comparison, no differences were found between these effective prophylactic strategies for preventing preeclampsia and pregnancy-induced hypertension, except with regard to exercise, which tended to be superior to aspirin and calcium supplementation in preventing pregnancy-induced hypertension. Furthermore, the prophylactic effects of aspirin and calcium supplementation were robust across subgroups. However, the prophylactic effects of low-molecular-weight heparin, exercise, and vitamin D supplementation on preeclampsia and pregnancy-induced hypertension varied with different risk populations, dosages, areas, etc. The certainty of the evidence was moderate to very low. CONCLUSION: Low-molecular-weight heparin, vitamin D supplementation, exercise, calcium supplementation, and aspirin reduce the risk of preeclampsia/pregnancy-induced hypertension. No significant differences between effective prophylactic strategies were found in preventing preeclampsia. These findings raise the necessity to reevaluate the prophylactic effects of low-molecular-weight heparin, vitamin D supplementation, and exercise on preeclampsia.

Force-triggered rapid microstructure growth on hydrogel surface for on-demand functions.

Living organisms share the ability to grow various microstructures on their surface to achieve functions. Here we present a force stamp method to grow microstructures on the surface of hydrogels based on a force-triggered polymerisation mechanism of double-network hydrogels. This method allows fast spatial modulation of the morphology and chemistry of the hydrogel surface within seconds for on-demand functions. We demonstrate the oriented growth of cells and directional transportation of water droplets on the engineered hydrogel surfaces. This force-triggered method to chemically engineer the hydrogel surfaces provides a new tool in addition to the conventional methods using light or heat, and will promote the wide application of hydrogels in various fields.