Soft robotic artificial left ventricle simulator capable of reproducing myocardial biomechanics.

The heart's intricate myocardial architecture has been called the Gordian knot of anatomy, an impossible tangle of intricate muscle fibers. This complexity dictates equally complex cardiac motions that are difficult to mimic in physical systems. If these motions could be generated by a robotic system, then cardiac device testing, cardiovascular disease studies, and surgical procedure training could reduce their reliance on animal models, saving time, costs, and lives.

PoroFluidics: deterministic fluid control in porous microfluidics.

Microfluidic devices with open lattice structures, equivalent to a type of porous media, allow for the manipulation of fluid transport processes while having distinct structural, mechanical, and thermal properties. However, a fundamental understanding of the design principles for the solid structure in order to achieve consistent and desired flow patterns remains a challenge, preventing its further development and wider applications. Here, through quantitative and mechanistic analyses of the behavior of multi-phase phenomena that involve gas-liquid-solid interfaces, we present a design framework for microfluidic devices containing porous architectures (referred to as poroFluidics) for deterministic control of multi-phase fluid transport processes.

Crawling, climbing, perching, and flying by FiBa soft robots.

This paper introduces an approach to fabricating lightweight, untethered soft robots capable of diverse biomimetic locomotion. Untethering soft robotics from electrical or pneumatic power remains one of the prominent challenges within the field. The development of functional untethered soft robotic systems hinges heavily on mitigating their weight; however, the conventional weight of pneumatic network actuators (pneu-nets) in soft robots has hindered untethered operations.

Liver click dECM hydrogels for engineering hepatic microenvironments.

Decellularized extracellular matrix (dECM) hydrogels provide tissue-specific microenvironments which accommodate physiological cellular phenotypes in 3D in vitro cell cultures. However, their formation hinges on collagen fibrillogenesis, a complex process which limits regulation of physicochemical properties. Hence, achieving reproducible results with dECM hydrogels poses as a challenge.

Development of a Probability-Based In Vitro Eye Irritation Screening Platform.

Traditional eye irritation assessments, which rely on animal models or ex vivo tissues, face limitations due to ethical concerns, costs, and low throughput. Although numerous in vitro tests have been developed, none have successfully reconciled the need for high experimental throughput with the accurate prediction of irritation potential, attributable to the complexity of irritation mechanisms. Simple cell models, while suitable for high-throughput screening, offer limited mechanistic insights, contrasting with more physiologically relevant but less scalable complex organotypic corneal tissue constructs.

An AI-assisted integrated, scalable, single-cell phenomic-transcriptomic platform to elucidate intratumor heterogeneity against immune response.

We present a novel framework combining single-cell phenotypic data with single-cell transcriptomic analysis to identify factors underpinning heterogeneity in antitumor immune response. We developed a pairwise, tumor-immune discretized interaction assay between natural killer (NK-92MI) cells and patient-derived head and neck squamous cell carcinoma (HNSCC) cell lines on a microfluidic cell-trapping platform. Furthermore we generated a deep-learning computer vision algorithm that is capable of automating the acquisition and analysis of a large, live-cell imaging data set (>1 million) of paired tumor-immune interactions spanning a time course of 24 h across multiple HNSCC lines ( = 10).

FEZ1 participates in human embryonic brain development by modulating neuronal progenitor subpopulation specification and migrations.

Mutations in the human fasciculation and elongation protein zeta 1 ( gene are found in schizophrenia and Jacobsen syndrome patients. Here, using human cerebral organoids (hCOs), we show that expression is turned on early during brain development and is detectable in both neuroprogenitor subtypes and immature neurons. FEZ1 deletion disrupts expression of neuronal and synaptic development genes.

Preferential adhesion of bacterial cells onto top- and bottom-mounted nanostructured surfaces under flow conditions.

The bactericidal effect of biomimetic nanostructured surfaces has been known for a long time, with recent data suggesting an enhanced efficiency of the nanostructured surfaces under fluid shear. While some of the influential factors on the bactericidal effect of nanostructured surfaces under fluid shear are understood, there are numerous important factors yet to be studied, which is essential for the successful implementation of this technology in industrial applications. Among those influential factors, the orientation of the nanostructured surface can play an important role in bacterial cell adhesion onto surfaces.

3D-printed biomimetic scaffolds with precisely controlled and tunable structures guide cell migration and promote regeneration of osteochondral defect.

Untreated osteochondral defects will develop into osteoarthritis, affecting patients' quality of life. Since articular cartilage and subchondral bone exhibit distinct biological characteristics, repairing osteochondral defects remains a major challenge. Previous studies have tried to fabricate multilayer scaffolds with traditional methods or 3D printing technology.

Vat photopolymerization 3D printed microfluidic devices for organ-on-a-chip applications.

Organs-on-a-chip, or OoCs, are microfluidic tissue culture devices with micro-scaled architectures that repeatedly achieve biomimicry of biological phenomena. They are well positioned to become the primary pre-clinical testing modality as they possess high translational value. Current methods of fabrication have facilitated the development of many custom OoCs that have generated promising results.

A User-Centric 3D-Printed Modular Peristaltic Pump for Microfluidic Perfusion Applications.

Microfluidic organ-on-a-chip (OoC) technology has enabled studies on dynamic physiological conditions as well as being deployed in drug testing applications. A microfluidic pump is an essential component to perform perfusion cell culture in OoC devices. However, it is challenging to have a single pump that can fulfil both the customization function needed to mimic a myriad of physiological flow rates and profiles found in vivo and multiplexing requirements (i.

Gas-modulating microcapsules for spatiotemporal control of hypoxia.

Oxygen is a vital molecule involved in regulating development, homeostasis, and disease. The oxygen levels in tissue vary from 1 to 14% with deviations from homeostasis impacting regulation of various physiological processes. In this work, we developed an approach to encapsulate enzymes at high loading capacity, which precisely controls the oxygen content in cell culture.

Controlling Microenvironments with Organs-on-Chips for Osteoarthritis Modelling.

Osteoarthritis (OA) remains a prevalent disease affecting more than 20% of the global population, resulting in morbidity and lower quality of life for patients. The study of OA pathophysiology remains predominantly in animal models due to the complexities of mimicking the physiological environment surrounding the joint tissue. Recent development in microfluidic organ-on-chip (OoC) systems have demonstrated various techniques to mimic and modulate tissue physiological environments.

Bactericidal Efficacy of Nanostructured Surfaces Increases under Flow Conditions.

Bacterial colonization on solid surfaces creates enormous problems across various industries causing billions of dollars' worth of economic damages and costing human lives. Biomimicking nanostructured surfaces have demonstrated a promising future in mitigating bacterial colonization and related issues. The importance of this non-chemical method has been elevated due to bacterial evolvement into antibiotic and antiseptic-resistant strains.

A comparative study of tumour-on-chip models with patient-derived xenografts for predicting chemotherapy efficacy in colorectal cancer patients.

Inter-patient and intra-tumour heterogeneity (ITH) have prompted the need for a more personalised approach to cancer therapy. Although patient-derived xenograft (PDX) models can generate drug response specific to patients, they are not sustainable in terms of cost and time and have limited scalability. Tumour Organ-on-Chip (OoC) models are alternatives that can recapitulate some aspects of the 3D tumour microenvironment and can be scaled up for drug screening.

Biomimetic Vasculatures by 3D-Printed Porous Molds.

Despite recent advances in biofabrication, recapitulating complex architectures of cell-laden vascular constructs remains challenging. To date, biofabricated vascular models have not yet realized four fundamental attributes of native vasculatures simultaneously: freestanding, branching, multilayered, and perfusable. In this work, a microfluidics-enabled molding technique combined with coaxial bioprinting to fabricate anatomically relevant, cell-laden vascular models consisting of hydrogels is developed.

Fluid Flow Induces Differential Detachment of Live and Dead Bacterial Cells from Nanostructured Surfaces.

Nanotopographic surfaces are proven to be successful in killing bacterial cells upon contact. This non-chemical bactericidal property has paved an alternative way of fighting bacterial colonization and associated problems, especially the issue of bacteria evolving resistance against antibiotic and antiseptic agents. Recent advancements in nanotopographic bactericidal surfaces have made them suitable for many applications in medical and industrial sectors.

Highly-customizable 3D-printed peristaltic pump kit.

Commercially available peristaltic pumps for microfluidics are usually bulky, expensive, and not customizable. Herein, we developed a cost-effective kit to build a micro-peristaltic pump (~ 50 USD) consisting of 3D-printed and off-the-shelf components. We demonstrated fabricating two variants of pumps with different sizes and operating flowrates using the developed kit.

Integration of a microfluidic multicellular coculture array with machine learning analysis to predict adverse cutaneous drug reactions.

Adverse cutaneous reactions are potentially life-threatening skin side effects caused by drugs administered into the human body. The availability of a human-specific platform that can prospectively screen drugs and predict this risk is therefore of great importance to drug safety. However, since adverse cutaneous drug reactions are mediated by at least 2 distinct mechanisms, both involving systemic interactions between liver, immune and dermal tissues, existing skin models have not been able to comprehensively recapitulate these complex, multi-cellular interactions to predict the skin-sensitization potential of drugs.

Design and fabrication of micro/nanofluidics devices and systems.

This chapter provides an overview of the science, engineering, and design methods required in the development of micro/nanofluidic devices. Section 2 provides the scientific background of fluid mechanics and physical phenomena in micro/nanoscale. Section 3 gives a brief overview of the existing fabrication techniques employed in micro/nanofluidics.

Bridging the academia-to-industry gap: organ-on-a-chip platforms for safety and toxicology assessment.

Some organ-on-a-chip (OoC) systems for drug evaluation show better predictive capabilities than planar, static cell cultures and animal models. One of the ongoing initiatives led by OoC developers is to bridge the academia-to-industry gap in the hope of gaining wider adoption by end-users - academic biological researchers and industry. We discuss several recommendations that can help to drive the adoption of OoC systems by the market.

Enhancement of Endothelialization by Topographical Features Is Mediated by PTP1B-Dependent Endothelial Adherens Junctions Remodeling.

Endothelial Cells (ECs) form cohesive cellular lining of the vasculature and play essential roles in both developmental processes and pathological conditions. Collective migration and proliferation of endothelial cells (ECs) are key processes underlying endothelialization of vessels as well as vascular graft, but the complex interplay of mechanical and biochemical signals regulating these processes are still not fully elucidated. While surface topography and biochemical modifications have been used to enhance endothelialization , thus far such single-modality modifications have met with limited success.

A Micropatterned Human-Specific Neuroepithelial Tissue for Modeling Gene and Drug-Induced Neurodevelopmental Defects.

The generation of structurally standardized human pluripotent stem cell (hPSC)-derived neural embryonic tissues has the potential to model genetic and environmental mediators of early neurodevelopmental defects. Current neural patterning systems have so far focused on directing cell fate specification spatio-temporally but not morphogenetic processes. Here, the formation of a structurally reproducible and highly-organized neuroepithelium (NE) tissue is directed from hPSCs, which recapitulates morphogenetic cellular processes relevant to early neurulation.