Strong, tough, rapid-recovery, and fatigue-resistant hydrogels made of picot peptide fibres.

Hydrogels are promising soft materials as tissue engineering scaffolds, stretchable sensors, and soft robotics. Yet, it remains challenging to develop synthetic hydrogels with mechanical stability and durability similar to those of the connective tissues. Many of the necessary mechanical properties, such as high strength, high toughness, rapid recovery, and high fatigue resistance, generally cannot be established together using conventional polymer networks. Here we present a type of hydrogels comprising hierarchical structures of picot fibres made of copper-bound self-assembling peptide strands with zipped flexible hidden length. The redundant hidden lengths allow the fibres to be extended to dissipate mechanical load without reducing network connectivity, making the hydrogels robust against damage. The hydrogels possess high strength, good toughness, high fatigue threshold, and rapid recovery, comparable to or even outperforming those of articular cartilage. Our study highlights the unique possibility of tailoring hydrogel network structures at the molecular level to improve their mechanical performance.

Effect of Superheat Steam on Ejector in Distilled Water Preparation System for Medical Injection.

In this study, a wet steam model was used to investigate the effect of steam superheat on ejector performance and non-equilibrium condensation phenomena. The simulation data for the ejector were validated with experimental data. The simulations show that an increase in primary flow superheat will increase the entrainment ratio, while an increase in secondary flow superheat will decrease the entrainment ratio. The output fluid superheat has little effect on the entrainment ratio. As the primary flow superheat increases from 0 to 20 K, the starting position of non-equilibrium condensation moves backward by 5 mm, and the mass fraction of condensed droplets decreases by 20%. The higher the secondary flow superheat, the lower the mass fraction of liquid in the diffusion chamber. The superheat level of the output fluid has no influence on the non-equilibrium condensation phenomenon of the ejector.

Gradual Stress-Relaxation of Hydrogel Regulates Cell Spreading.

There is growing evidence that the mechanical properties of extracellular matrices (ECMs), including elasticity and stress-relaxation, greatly influence the function and form of the residing cells. However, the effects of elasticity and stress-relaxation are often correlated, making the study of the effect of stress-relaxation on cellular behaviors difficult. Here, we designed a hybrid network hydrogel with a controllable stress-relaxation gradient and a constant elasticity. The hydrogel is crosslinked by covalent bonds and dynamic peptide-metal ion coordination interactions. The stress-relaxation gradient is controlled by spatially controlling the coordination and covalent crosslinker ratios. The different parts of the hydrogel exhibit distinct stress-relaxation amplitudes but the have same stress-relaxation timescale. Based on this hydrogel, we investigate the influence of hydrogel stress-relaxation on cell spreading. Our results show that the spreading of cells is suppressed at an increasing stress-relaxation amplitude with a fixed elasticity and stress-relaxation timescale. Our study provides a universal route to tune the stress-relaxation of hydrogels without changing their components and elasticity, which may be valuable for systematic investigations of the stress-relaxation gradient in cell cultures and organoid constructions.

Strong and Reversible Covalent Double Network Hydrogel Based on Force-Coupled Enzymatic Reactions.

Biological load-bearing tissues are strong, tough, and recoverable under periodic mechanical loads. However, such features have rarely been achieved simultaneously in the same synthetic hydrogels. Here, we use a force-coupled enzymatic reaction to tune a strong covalent peptide linkage to a reversible bond. Based on this concept we engineered double network hydrogels that combine high mechanical strength and reversible mechanical recovery in the same hydrogels. Specifically, we found that a peptide ligase, sortase A, can promote the proteolysis of peptides under force. The peptide bond can be re-ligated by the same enzyme in the absence of force. This allows the sacrificial network in the double-network hydrogels to be ruptured and rebuilt reversibly. Our results demonstrate a general approach for precisely controlling the mechanical and dynamic properties of hydrogels at the molecular level.

Biophysical Approaches for Applying and Measuring Biological Forces.

Over the past decades, increasing evidence has indicated that mechanical loads can regulate the morphogenesis, proliferation, migration, and apoptosis of living cells. Investigations of how cells sense mechanical stimuli or the mechanotransduction mechanism is an active field of biomaterials and biophysics. Gaining a further understanding of mechanical regulation and depicting the mechanotransduction network inside cells require advanced experimental techniques and new theories. In this review, the fundamental principles of various experimental approaches that have been developed to characterize various types and magnitudes of forces experienced at the cellular and subcellular levels are summarized. The broad applications of these techniques are introduced with an emphasis on the difficulties in implementing these techniques in special biological systems. The advantages and disadvantages of each technique are discussed, which can guide readers to choose the most suitable technique for their questions. A perspective on future directions in this field is also provided. It is anticipated that technical advancement can be a driving force for the development of mechanobiology.

Molecular engineering of metal coordination interactions for strong, tough, and fast-recovery hydrogels.

Many load-bearing tissues, such as muscles and cartilages, show high elasticity, toughness, and fast recovery. However, combining these mechanical properties in the same synthetic biomaterials is fundamentally challenging. Here, we show that strong, tough, and fast-recovery hydrogels can be engineered using cross-linkers involving cooperative dynamic interactions. We designed a histidine-rich decapeptide containing two tandem zinc binding motifs. Because of allosteric structural change-induced cooperative binding, this decapeptide had a higher thermodynamic stability, stronger binding strength, and faster binding rate than single binding motifs or isolated ligands. The engineered hybrid network hydrogels containing the peptide-zinc complex exhibit a break stress of ~3.0 MPa, toughness of ~4.0 MJ m-3, and fast recovery in seconds. We expect that they can function effectively as scaffolds for load-bearing tissue engineering and as building blocks for soft robotics. Our results provide a general route to tune the mechanical and dynamic properties of hydrogels at the molecular level.

Identification of malignant early repolarization pattern by late QRS activity in high-resolution magnetocardiography.

BACKGROUND: The early repolarization pattern (ERP) in electrocardiography (ECG) has been considered as a risk for ventricular fibrillation (VF), but effective methods for identification of malignant ERP are still required. We investigated whether high spatiotemporal resolution 64-channel magnetocardiography (MCG) would enable distinction between benign and malignant ERPs. METHODS: Among all 2,636 subjects who received MCG in our facility, we identified 116 subjects (43 ± 18 years old, 54% male) with inferior and/or lateral ERP in ECG and without structural heart disease, including 13 survivors of VF (ERP-VF(+)) and 103 with no history of VF (ERP-VF(-)). We measured the following MCG parameters in a time-domain waveform of relative current magnitude: (a) QRS duration (MCG-QRSD), (b) root-mean-square of the last 40 ms (MCG-RMS40), and (c) low amplitude (<10% of maximal) signal duration (MCG-LAS). RESULTS: Compared to ERP-VF(-), ERP-VF(+) subjects presented a significantly longer MCG-QRS (108 ± 24 vs. 91 ± 23 ms, p = .02) and lower MCG-RMS40 (0.10 ± 0.08 vs. 0.25 ± 0.20, p = .01) but no difference in MCG-LAS (38 ± 22 vs. 29 ± 23 ms, p = .17). MCG-QRSD and MCG-RMS40 showed significantly larger area under the ROC curve compared to J-peak amplitude in ECG (0.72 and 0.71 vs. 0.50; p = .04 and 0.03). The sensitivity, specificity, and odds ratio for identifying VF(+) based on MCG-QRSD ≥ 100 ms and MCG-RMS40 ≤ 0.24 were 69%, 74%, and 6.33 (95% CI, 1.80-22.3), and 92%, 48%, and 10.9 (95% CI, 1.37-86.8), respectively. CONCLUSION: Magnetocardiography is an effective tool to distinguish malignant and benign ERPs.

An Injectable Self-Healing Protein Hydrogel with Multiple Dissipation Modes and Tunable Dynamic Response.

Hydrogels with dynamic mechanical properties are of special interest in the field of tissue engineering and drug delivery. However, it remains challenging to tailor the dynamic mechanical response of hydrogels to simultaneously meet diverse application needs. Here, we report a hetero-coiled-coil complex cross-linked protein hydrogel exhibiting unusual multiple energy dissipation modes and tunable dynamic response. Such unique features confer on the hydrogel responsiveness to mechanical stimuli in a broad range of frequencies. Therefore, the hydrogels are injectable due to their shearing-thinning properties at low shear rates of 0.8 rad s-1 and can fully recover their mechanical properties within a few seconds due to the intrinsic fast dynamics of the cross-linkers. Moreover, the dynamic response of these hydrogels can be fine-tuned by the temperature and the hydrogel network structures. We anticipate that these hydrogels are promising candidates for delivering therapeutic drugs, biological molecules, and cells in a broad spectrum of biomedical applications.

Tuning of the dynamics of metal ion crosslinked hydrogels by network structures.

The dynamic mechanical response of hydrogels is correlated with the intrinsic dynamics of the crosslinkers. Our experiments and theory show that polymer network structures can also affect the dynamic response of hydrogels by transducing swelling forces to the crosslinkers. Our results suggest a novel route to engineer complex time-dependent mechanical properties of soft materials for biomedical applications.