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This cross-journal collection on “Microphysiological Systems” is a collaboration between Nature Communications, Communications Biology, Communications Engineering and Scientific Reports. Microphysiological Systems feature the culture of cells, tissues or organoids inside of biomimetic microfluidic devices that aim to recapitulate the circulation and interconnection between different organs found within the human body. These platforms modeling (patho)physiological processes promise to revolutionize basic research as well as drug development and screening, while enabling personalized medicine and reducing our reliance on animal experiments. Within this field, we look forward to seeing submissions on the sub-topics of, but not exclusively on, Engineering Advances, Modeling Biological Phenomena, and Modelling Disease & Drug Testing.
Ishan Goswami and colleagues report engineering robust physiologically relevant tissues in microphysiological systems utilizing highly tuneable interfacial barriers. This has applications for drug discovery and disease modelling.
Thomas Chen and colleagues design a microphysiological system for the study of intestinal mouse epithelial tissue under physiological conditions in an ex-vivo environment. Using their apparatus they perform a time-dependent analysis of the transepithelial electrical resistance and determine changes in the gut epithelial barrier permeability.
Hydrogels capable of swift mechanical energy dissipation are desirable for various uses, but traditional energy absorption in hydrogels typically relies on viscoelastic mechanisms and often suffers from slow recovery. Here, the authors report a hydrogel design harnessing molecular friction to achieve efficient energy dissipation and rapid recovery.
Suture repair is the current clinical treatment for meniscus tears, but inaccessible tears in company with re-tears susceptibility remain unresolved. Here the authors address these issues by developing a meniscus adhesive-based strategy for the seamless and dense reconstruction of torn meniscus.
Leendert-Jan W. Ligtenberg and colleagues report an X-ray guided platform for the wireless teleoperation of hemocompatible, untethered magnetic robots. The approach will enable clinicians to reach and treat vascular diseases within the body where alternative tethered flexible surgical instruments offer more limited control.
Nidhi Sinha, Haowen Yang and colleagues report a microfluidic large-scale integration chip to probe temporal single-cell signalling networks via the delivery of patterns of input signalling molecules. The researchers use their device to investigate drug-induced cancer cell apoptosis and single cell transcription (STAT-1) protein signalling dynamics.
GPR35 controls the transmembrane ion gradient by regulating Na/K-ATPase function with knock-on effects on osmosis, cellular stress and glutamine uptake.
The ability to maintain blood stem cells (HSCs) in vitro would allow us to provide better therapies for blood diseases. Here, the authors report that polymer-organised extracellular proteins, coupled to soft environments mimicking bone marrow stiffness, allow stromal cells to maintain HSCs in vitro.
Generating 3D bone cell networks in vitro that mimic the dynamic process during early bone formation is vital for creating in vitro models of bone development for disease modeling and drug testing, but remains challenging. Herein, the authors report a synthetic biodegradable microporous hydrogel for in vitro generation of functional human bone cell networks in 3D and microfluidic integration.
The functional heterogeneity of autophagy in endothelial cells during angiogenesis remains incompletely understood. Here, the authors apply a 3D angiogenesis-on-a-chip coupled with single-cell RNA sequencing to find distinct autophagy functions in two different endothelial cell populations during angiogenic sprouting.
Nguyen and colleagues report a microfluidic platform with a ladder shaped design which identifies bacterial susceptibility to antibiotics in less than 5 h. The device could assist physicians and veterinarians to make more targeted and rapid prescriptions for antibiotic infections.
Skin-nerve crosstalk is a major element of skin physiological pathology. Here the authors report a 3D innervated epidermal keratinocyte layer as a sensory neuron-epidermal keratinocyte coculture model on a microfluidic chip using the slope-based air-liquid interfacing culture and spatial compartmentalization.
Normal and abnormal pregnancy is challenging to study and involves complex interactions between maternal and fetal cells. Here the authors present an implantation-on-a-chip device capable of modeling trophoblast invasion, a process critical to the establishment of pregnancy.
Anika Alim and colleagues micro engineered a 3D vascularized midbrain model that emulates the capillary interface of midbrain dopaminergic neurons. This approach accurately recapitulates key Parkinson’s disease pathologies, including neurodegeneration and vascular regression.
The authors developed a patient-specific microphysiological system using the LumeNEXT microfluidic platform to more accurately recreate the prostate cancer metastatic bone tumor microenvironment.
Watmuff et al. show that drug treatments like carbamazepine reduce hyperactivity and improve goal-directed performance in a neural microphysiological system (DishBrain), suggesting its potential for studying drug effects on information processing.
Biophysical modeling combined with simulation-based inference enables the extraction of mechanistic insights from MEA data, revealing the molecular mechanisms underlying altered network activity patterns of patient-derived neurons.
Human bone marrow MPS enables in vitro profiling of hematopoietic and immunotoxic effects of biologics, capturing lineage-specific responses and T cell–mediated cytotoxicity in a microfluidic system with optional autologous immune components.
Human liver portal fibroblasts can enhance and stabilize the functions of primary human hepatocytes in both 2-dimensional and 3-dimensional culture formats, and such occurs partly due to insulin-like growth factor binding protein 5 signaling.
Generation of a midbrain-striatum assembloid with progerin overexpression as an in vitro model of possessing aging and senescence characteristics for studying Parkinson’s disease.
A coupled liver-islet MPS was used to investigate the comorbidity between MASLD and T2DM. This study demonstrated that secreted factors from the MASLD liver disrupt islet function and suggest potential underlying mechanisms of disease progression along the liver-islet axis.
In vitro modelling of the adipose tissue-liver axis can advance understanding and therapy of metabolic disease, including by distinguishing effects of obesity and inflammation. Here, authors develop such a system based on isogenic human iPSCs and interconnected microphysiological devices.
The interplay between blood vessel (BV) and epithelial tissue is crucial for organogenesis. Here, the authors co-culture hiPSC-derived liver progenitors on artificial BV to establish functional human bile ducts for modeling congenital biliary disease.
Hepatocellular carcinoma is the most common type of primary liver cancer. Here the authors show an oxygen gradient chip that separates aggressive hepatocellular carcinoma cells from a heterogeneous tumor mass, mirroring the conditions of the portal vein, hepatic artery, and liver.
Bioprinting has revitalized tissue regeneration efforts, yet challenges persist due to cell damage during fabrication and mechanical instability of printed scaffolds. Here, the authors develop a mechanical-assisted post-bioprinting strategy for loading cells into hollow scaffolds that effectively repair challenging bone defects.
The application of engineered cardiac tissues is limited due to their immaturity and lack of functionality. Here, the authors develop an integrated culture platform featuring heart extracellular matrix cultured in a microfluidic chip to facilitate cardiac tissue development for versatile biomedical applications.
Here the authors develop perfusable inner blood-retinal barrier-specific microvascular networks with human primary retinal microvascular cells. They show that chronic diabetic stimulation leads to the generation of early hallmarks of diabetic retinopathy, including pericyte and capillary dropout, ghost vessels, and inflammation.
A unique 3D-printed device made of sustainable materials was developed to produce 3D spheroids from primary cells and perform drug screening assays in a biomimetic environment.
Acute exposure to radiation can lead to acute pneumonitis, fibrosis or death. Here the authors develop an alveolus-on chip model to study the molecular characteristics of radiation induced lung injury, better understand radiation induced lung disease and facilitate drug screening.
A model system for studying non-alcoholic fatty liver disease is created by co-culturing human gut and liver cell lines in a closed circulation loop using microfluidics.
A biomimetic inducible model of pulmonary arterial hypertension (PAH) is presented, combining natural and induced BMPR2 dysfunction with hypoxia in lung endothelial cells and blood-derived PAH cells to induce smooth muscle activation & proliferation.
Understanding host responses to Herpes simplex virus (HSV) in humans is challenging. Here the authors report a vascularised 3D ‘skin-on-chip’ that mimics human skin architecture and is competent to immune-cell and drug perfusion; they use this to model HSV infection.