Heart-on-a-chip systems with tissue-specific functionalities for physiological, pathological, and pharmacological studies.

Recent advances in heart-on-a-chip systems hold great promise to facilitate cardiac physiological, pathological, and pharmacological studies. This review focuses on the development of heart-on-a-chip systems with tissue-specific functionalities. For one thing, the strategies for developing cardiac microtissues on heart-on-a-chip systems that closely mimic the structures and behaviors of the native heart are analyzed, including the imitation of cardiac structural and functional characteristics. For another, the development of techniques for real-time monitoring of biophysical and biochemical signals from cardiac microtissues on heart-on-a-chip systems is introduced, incorporating cardiac electrophysiological signals, contractile activity, and biomarkers. Furthermore, the applications of heart-on-a-chip systems in intelligent cardiac studies are discussed regarding physiological/pathological research and pharmacological assessment. Finally, the future development of heart-on-a-chip toward a higher level of systematization, integration, and maturation is proposed.

Coaxial Electrohydrodynamic Printing of Microscale Core-Shell Conductive Features for Integrated Fabrication of Flexible Transparent Electronics.

Reliable insulation of microscale conductive features is required to fabricate functional multilayer circuits or flexible electronics for providing specific physical/chemical/electrical protection. However, the existing strategies commonly rely on manual assembling processes or multiple microfabrication processes, which is time-consuming and a great challenge for the fabrication of flexible transparent electronics with microscale features and ultrathin thickness. Here, we present a novel coaxial electrohydrodynamic (CEHD) printing strategy for the one-step fabrication of microscale flexible electronics with conductive materials at the core and insulating material at the outer layer. A finite element analysis (FEA) method is established to simulate the CEHD printing process. The extrusion sequence of the conductive and insulating materials during the CEHD printing process shows little effect on the morphology of the core-shell filaments, which can be achieved on different flexible substrates with a minimum conductive line width of 32 ± 3.2 µm, a total thickness of 53.6 ± 4.8 µm, and a conductivity of 0.23 × 107 S/m. The thin insulating layer can provide the inner conductive filament enough protection in 3D, which endows the resultant microscale core-shell electronics with good electrical stability when working in different chemical solvent solutions or under large deformation conditions. Moreover, the presented CEHD printing strategy offers a unique capability to sequentially fabricate an insulating layer, core-shell conductive pattern, and exposed electrodes by simply controlling the material extrusion sequence. The resultant large-area transparent electronics with two-layer core-shell patterns exhibit a high transmittance of 98% and excellent electrothermal performance. The CEHD-printed flexible microelectrode array is successfully used to record the electrical signals of beating mouse hearts. It can also be used to fabricate large-area flexible capacitive sensors to accurately measure the periodical pressure force. We envision that the present CEHD printing strategy can provide a promising tool to fabricate complex three-dimensional electronics with microscale resolution, high flexibility, and multiple functionalities.

Advancing Intelligent Organ-on-a-Chip Systems with Comprehensive In Situ Bioanalysis.

In vitro models are essential to a broad range of biomedical research, such as pathological studies, drug development, and personalized medicine. As a potentially transformative paradigm for 3D in vitro models, organ-on-a-chip (OOC) technology has been extensively developed to recapitulate sophisticated architectures and dynamic microenvironments of human organs by applying the principles of life sciences and leveraging micro- and nanoscale engineering capabilities. A pivotal function of OOC devices is to support multifaceted and timely characterization of cultured cells and their microenvironments. However, in-depth analysis of OOC models typically requires biomedical assay procedures that are labor-intensive and interruptive. Herein, the latest advances toward intelligent OOC (iOOC) systems, where sensors integrated with OOC devices continuously report cellular and microenvironmental information for comprehensive in situ bioanalysis, are examined. It is proposed that the multimodal data in iOOC systems can support closed-loop control of the in vitro models and offer holistic biomedical insights for diverse applications. Essential techniques for establishing iOOC systems are surveyed, encompassing in situ sensing, data processing, and dynamic modulation. Eventually, the future development of iOOC systems featuring cross-disciplinary strategies is discussed.

Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities.

Recapitulating the complex structural, mechanical, and electrophysiological properties of native myocardium is crucial to engineering functional cardiac tissues. Here, we report a leaf-venation-directed strategy that enables the compaction and remodeling of cell-hydrogel hybrids into highly aligned and densely packed organizations in predetermined patterns. This strategy contributes to interconnected tubular structures with cell alignment along the hierarchical channels. Compared to randomly-distributed cells, the engineered leaf-venation-directed-cardiac tissues from neonatal rat cardiomyocytes manifest advanced maturation and functionality as evidenced by detectable electrophysiological activity, macroscopically synchronous contractions, and upregulated maturation genes. As a demonstration, human induced pluripotent stem cell-derived leaf-venation-directed-cardiac tissues are engineered with evident structural and functional improvement over time. With the elastic scaffolds, leaf-venation-directed tissues are assembled into 3D centimeter-scale cardiac constructs with programmed mechanical properties, which can be delivered through tubing without affecting cell viability. The present strategy may generate cardiac constructs with multifaceted functionalities to meet clinical demands.

Correction: Zhu et al. Electroactive Oxidized Alginate/Gelatin/MXene (Ti3C2Tx) Composite Hydrogel with Improved Biocompatibility and Self-Healing Property. Polymers 2022, 14, 3908.

In the original publication [...].

Electroactive Oxidized Alginate/Gelatin/MXene (Ti3C2Tx) Composite Hydrogel with Improved Biocompatibility and Self-Healing Property.

Conductive hydrogels (CHs) have shown promising potential applied as wearable or epidermal sensors owing to their mechanical adaptability and similarity to natural tissues. However, it remains a great challenge to develop an integrated hydrogel combining outstanding conductive, self-healing and biocompatible performances with simple approaches. In this work, we propose a "one-pot" strategy to synthesize multifunctional CHs by incorporating two-dimensional (2D) transition metal carbides/nitrides (MXenes) multi-layer nano-flakes as nanofillers into oxidized alginate and gelatin hydrogels to form the composite CHs with various MXene contents. The presence of MXene with abundant surface groups and outstanding conductivity could improve the mechanical property and electroactivity of the composite hydrogels compared to pure oxidized alginate dialdehyde-gelatin (ADA-GEL). MXene-ADA-GELs kept good self-healing properties due to the dynamic imine linkage of the ADA-GEL network and have a promoting effect on mouse fibroblast (NH3T3s) attachment and spreading, which could be a result of the integration of MXenes with stimulating conductivity and hydrophily surface. This study suggests that the electroactive MXene-ADA-GELs can serve as an appealing candidate for skin wound healing and flexible bio-electronics.