Biomaterials currently used in cardiac tissue engineering have certain limitations, such as lack of electrical conductivity and appropriate mechanical properties, which are two parameters playing a key role in regulating cardiac cellular behavior. In this work, we engineered myocardial tissue constructs based on reduced graphene oxide (rGO)-incorporated gelatin methacrylyol (GelMA) hybrid hydrogels. The incorporation of rGO into the GelMA matrix significantly enhanced the electrical conductivity and mechanical properties of the material. Moreover, cells cultured on composite rGO-GelMA scaffolds exhibited better biological activities such as cell viability, proliferation, and maturation compared to ones cultured on GelMA hydrogels. Cardiomyocytes showed stronger contractility and faster spontaneous beating rate on rGO-GelMA hydrogel sheets compared to those on pristine GelMA hydrogels, as well as GO-GelMA hydrogel sheets with similar mechanical property and particle concentration. Our strategy of integrating rGO within a biocompatible hydrogel is expected to be broadly applicable for future biomaterial design to improve tissue engineering outcomes. The engineered cardiac tissue constructs using rGO incorporated hybrid hydrogels can potentially provide high-fidelity tissue models for drug studies and the investigations of cardiac tissue development and/or disease processes in vitro.

A highly elastic hybrid hydrogel of methacryloyl‐substituted recombinant human tropoelastin (MeTro) and graphene oxide (GO) nanoparticles are developed. The synergistic effect of these two materials significantly enhances both ultimate strain (250%), reversible rotation (9700°), and the fracture energy (38.8 ± 0.8 J m−2) in the hybrid network. Furthermore, improved electrical signal propagation and subsequent contraction of the muscles connected by hybrid hydrogels are observed in ex vivo tests.

Excessive inflammation and failed resolution of the inflammatory response are underlying components of numerous conditions such as arthritis, cardiovascular disease, and cancer. Hence, therapeutics that dampen inflammation and enhance resolution are of considerable interest. In this study, we demonstrate the proresolving activity of sub-100-nm nanoparticles (NPs) containing the anti-inflammatory peptide Ac2-26, an annexin A1/lipocortin 1-mimetic peptide. These NPs were engineered using biodegradable diblock poly(lacticco-glycolic acid)-b-polyethyleneglycol and poly(lactic-co-glycolic acid)-b-polyethyleneglycol collagen IV-targeted polymers. Using a self-limited zymosan-induced peritonitis model, we show that the Ac2-26 NPs (100 ng per mouse) were significantly more potent than Ac2-26 native peptide at limiting recruitment of polymononuclear neutrophils (56% vs. 30%) and at decreasing the resolution interval up to 4 h. Moreover, systemic administration of collagen IV targeted Ac2-26 NPs (in as low as 1 μg peptide per mouse) was shown to significantly block tissue damage in hind-limb ischemiareperfusion injury by up to 30% in comparison with controls.Together, these findings demonstrate that Ac2-26 NPs are proresolving in vivo and raise the prospect of their use in chronic inflammatory diseases such as atherosclerosis.nanomedicine | nanotechnology | controlled release | inflammation resolution

Myocardial microenvironment plays a decisive role in guiding the function and fate of cardiomyocytes, and engineering this extracellular niche holds great promise for cardiac tissue regeneration. Platforms utilizing hybrid hydrogels containing various types of conductive nanoparticles have been a critical tool for constructing engineered cardiac tissues with outstanding mechanical integrity and improved electrophysiological properties. However, there has been no attempt to directly compare the efficacy of these hybrid hydrogels and decipher the mechanisms behind how these platforms differentially regulate cardiomyocyte behavior. Here, we employed gelatin methacryloyl (GelMA) hydrogels containing three different types of carbon-based nanoparticles: carbon nanotubes (CNTs), graphene oxide (GO), and reduced GO (rGO), to investigate the influence of these hybrid scaffolds on the structural organization and functionality of cardiomyocytes. Using immunofluorescent staining for assessing cellular organization and proliferation, we showed that electrically conductive scaffolds (CNT- and rGO-GelMA compared to relatively nonconductive GO-GelMA) played a significant role in promoting desirable morphology of cardiomyocytes and elevated the expression of functional cardiac markers, while maintaining their viability. Electrophysiological analysis revealed that these engineered cardiac tissues showed distinct cardiomyocyte phenotypes and different levels of maturity based on the substrate (CNT-GelMA: ventricular-like, GO-GelMA: atrial-like, and rGO-GelMA: ventricular/atrial mixed phenotypes). Through analysis of gene-expression patterns, we uncovered that the engineered cardiac tissues matured on CNT-GelMA and native cardiac tissues showed comparable expression levels of maturation markers. Furthermore, we demonstrated that engineered cardiac tissues matured on CNT-GelMA have increased functionality through integrin-mediated mechanotransduction (via YAP/TAZ) in contrast to cardiomyocytes cultured on rGO-GelMA.

A trial strain-monitoring system using Brillouin optical time-domain reflectometry (BOTDR) technology was set up to monitor joint movements in the concrete tunnel lining in an existing London Underground tunnel. The BOTDR strain sensor system allows the measurement of strain distribution along an optical fibre using the reflective technique, requiring access to only one end of the fibre. Measurements were obtained by a strain-sensing optical fibre installed along the tunnel lining. The joint movements were captured by measuring the strain along the fibre across the segment joints. The results show that there is good agreement between the joint movements evaluated by the BOTDR strain sensor system and those by conventional vibrating-wire strain gauges. Whereas conventional strain measurement gauges monitor the strain variations at discrete locations, a BOTDR strain sensor can provide a continuous strain distribution of the tunnel lining. The results demonstrate the practicality of using the BOTDR strain-sensing system to monitor the movement of tunnel linings.

Abstract

Cogent is a restricted functional language designed to reduce the cost of developing verified systems code. Because of its sometimes-onerous restrictions, such as the lack of support for recursion and its strict uniqueness type system, Cogent provides an escape hatch in the form of a foreign function interface (FFI) to C code. This poses a problem when verifying Cogent programs, as imported C components do not enjoy the same level of static guarantees that Cogent does. Previous verification of file systems implemented in Cogent merely assumed that their C components were correct and that they preserved the invariants of Cogent's type system. In this paper, we instead prove such obligations. We demonstrate how they smoothly compose with existing Cogent theorems, and result in a correctness theorem of the overall Cogent-C system. The Cogent FFI constraints ensure that key invariants of Cogent's type system are maintained even when calling C code. We verify reusable higher-order and polymorphic functions including a generic loop combinator and array iterators and demonstrate their application to several examples including binary search and the BilbyFs file system. We demonstrate the feasibility of verification of mixed Cogent-C systems, and provide some insight into verification of software comprised of code in multiple languages with differing levels of static guarantees.

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