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Abstract
The exploration of neural circuitry is paramount for comprehending the computational mechanisms and physiology of the brain. Despite significant advances in materials and fabrication techniques, controlling neuronal connectivity and response in 3D remains a formidable challenge. Here, we introduce a method for engineering the growth of 3D neural circuits with the capability for optical stimulation. We fabricate bioactive interfaces by melt electrospinning writing (MEW) 3D polycaprolactone (PCL) scaffolds followed by coating with titanium carbide (Ti3C2Tx MXene). Beyond enhancing hydrophilicity, cell adhesion, and electrical conductivity, the Ti3C2Tx MXene coating enables optocapacitance-based neuronal stimulation, induced by localized temperature increases upon illumination. This approach offers a pathway for additive manufacturing of neural tissues endowed with optical control, facilitating functional tissue engineering and neural circuit computation.

Abstract
Tetrapod-shaped ZnO (t-ZnO) microparticles create interconnected channels and textured surfaces in 3D-printed microstructured alginate (M-Alg) scaffolds.Primary mouse cortical neurons cultured on the M-Alg scaffolds demonstrate enhanced adhesion and maturation, with formation of extensive 3D neural projections, indicating the potential of this scaffold design for advanced neural tissue engineering applications.

Abstract
The successful translation of organ-on-a-chip devices requires the development of an automated workflow for device fabrication, which is challenged by the need for precise deposition of multiple classes of materials in micro-meter scaled configurations. Many current heart-on-a-chip devices are produced manually, requiring the expertise and dexterity of skilled operators. Here, we devised an automated and scalable fabrication method to engineer a Biowire II multiwell platform to generate human iPSC-derived cardiac tissues. This high-throughput heart-on-a-chip platform incorporated fluorescent nanocomposite microwires as force sensors, produced from quantum dots and thermoplastic elastomer, and 3D printed on top of a polystyrene tissue culture base patterned by hot embossing. An array of built-in carbon electrodes was embedded in a single step into the base, flanking the microwells on both sides. The facile and rapid 3D printing approach efficiently and seamlessly scaled up the Biowire II system from an 8-well chip to a 24-well and a 96-well format, resulting in an increase of platform fabrication efficiency by 17,5000–69,000% per well. The device's compatibility with long-term electrical stimulation in each well facilitated the targeted generation of mature human iPSC-derived cardiac tissues, evident through a positive force-frequency relationship, post-rest potentiation, and well-aligned sarcomeric apparatus. This system's ease of use and its capacity to gauge drug responses in matured cardiac tissue make it a powerful and reliable platform for rapid preclinical drug screening and development.

Abstract
Abstract Epicardial cells (EPIs) form the outer layer of the heart and play an important role in development and disease. Current heart-on-a-chip platforms still do not fully mimic the native cardiac environment due to the absence of relevant cell types, such as EPIs. Here, using the Biowire II platform, engineered cardiac tissues with an epicardial outer layer and inner myocardial structure are constructed, and an image analysis approach is developed to track the EPI cell migration in a beating myocardial environment. Functional properties of EPI cardiac tissues improve over two weeks in culture. In conditions mimicking ischemia reperfusion injury (IRI), the EPI cardiac tissues experience less cell death and a lower impact on functional properties. EPI cell coverage is significantly reduced and more diffuse under normoxic conditions compared to the post-IRI conditions. Upon IRI, migration of EPI cells into the cardiac tissue interior is observed, with contributions to alpha smooth muscle actin positive cell population. Altogether, a novel heart-on-a-chip model is designed to incorporate EPIs through a formation process that mimics cardiac development, and this work demonstrates that EPI cardiac tissues respond to injury differently than epicardium-free controls, highlighting the importance of including EPIs in heart-on-a-chip constructs that aim to accurately mimic the cardiac environment.

Abstract
Yolk sac macrophages are the first to seed the developing heart; however, owing to a lack of accessible tissue, there is no understanding of their roles in human heart development and function. In this study, we bridge this gap by differentiating human embryonic stem (hES) cells into primitive LYVE1+ macrophages (hESC-macrophages) that stably engraft within contractile cardiac microtissues composed of hESC-cardiomyocytes and fibroblasts. Engraftment induces a human fetal cardiac macrophage gene program enriched in efferocytic pathways. Functionally, hESC-macrophages trigger cardiomyocyte sarcomeric protein maturation, enhance contractile force and improve relaxation kinetics. Mechanistically, hESC-macrophages engage in phosphatidylserine-dependent ingestion of apoptotic cardiomyocyte cargo, which reduces microtissue stress, leading hESC-cardiomyocytes to more closely resemble early human fetal ventricular cardiomyocytes, both transcriptionally and metabolically. Inhibiting hESC-macrophage efferocytosis impairs sarcomeric protein maturation and reduces cardiac microtissue function. Together, macrophage-engineered human cardiac microtissues represent a considerably improved model for human heart development and reveal a major beneficial role for human primitive macrophages in enhancing early cardiac tissue function.

Abstract
Engineered neural tissues serve as models for studying neurological conditions and drug screening. Besides observing the cellular physiological properties, in situ monitoring of neurochemical concentrations with cellular spatial resolution in such neural tissues can provide additional valuable insights in models of disease and drug efficacy. In this work, we demonstrate the first three-dimensional (3D) tissue cultures with embedded optical dopamine (DA) sensors. We developed an alginate/Pluronic F127 based bio-ink for human dopaminergic brain tissue printing with tetrapodal-shaped-ZnO microparticles (t-ZnO) additive as the DA sensor. DA quenches the autofluorescence of t-ZnO in physiological environments, and the reduction of the fluorescence intensity serves as an indicator of the DA concentration. The neurons that were 3D printed with the t-ZnO showed good viability, and extensive 3D neural networks were formed within one week after printing. The t-ZnO could sense DA in the 3D printed neural network with a detection limit of 0.137 μM. The results are a first step toward integrating tissue engineering with intensiometric biosensing for advanced artificial tissue/organ monitoring.

Abstract
We developed a heart-on-a-chip platform that integrates highly flexible, vertical, 3D micropillar electrodes for electrophysiological recording and elastic microwires for the tissue’s contractile force assessment. The high aspect ratio microelectrodes were 3D-printed into the device using a conductive polymer, poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (PEDOT:PSS). A pair of flexible, quantum dots/thermoplastic elastomer nanocomposite microwires were 3D printed to anchor the tissue and enable continuous contractile force assessment. The 3D microelectrodes and flexible microwires enabled unobstructed human iPSC-based cardiac tissue formation and contraction, suspended above the device surface, under both spontaneous beating and upon pacing with a separate set of integrated carbon electrodes. Recording of extracellular field potentials using the PEDOT:PSS micropillars was demonstrated with and without epinephrine as a model drug, non-invasively, along with in situ monitoring of tissue contractile properties and calcium transients. Uniquely, the platform provides integrated profiling of electrical and contractile tissue properties, which is critical for proper evaluation of complex, mechanically and electrically active tissues, such as the heart muscle under both physiological and pathological conditions.

Abstract
Abstract Bioelastomers have been extensively used in biomedical applications due to their desirable mechanical strength, tunable properties, and chemical versatility; however, 3D printing bioelastomers into microscale structures has proven elusive. Herein, a high throughput omnidirectional printing approach via coaxial extrusion is described that fabricated perfusable elastomeric microtubes of unprecedently small inner diameter (350-550 μm) and wall thickness (40-60 μm). The versatility of this approach was shown through the printing of two different polymeric elastomers, followed by photocrosslinking and removal of the fugitive inner phase. Designed experiments were used to tune the dimensions and stiffness of the microtubes to match that of native ex vivo rat vasculature. This approach afforded the fabrication of multiple biomimetic shapes resembling cochlea and kidney glomerulus and afforded facile, high-throughput generation of perfusable structures that can be seeded with endothelial cells for biomedical applications. Post-printing laser micromachining was performed to generate numerous micro-sized holes (5-20 μm) in the tube wall to tune microstructure permeability. Importantly, for organ-on-a-chip applications, the described approach took only 3.6 minutes to print microtubes (without microholes) over an entire 96-well plate device, in contrast to comparable hole-free structures that take between 1.5 to 6.5 days to fabricate using a manual 3D stamping approach. This article is protected by copyright. All rights reserved