Abstract The term “cyborg” refers to a cybernetic organism, which characterizes the chimera of a living organism and a machine. Owing to the widespread application of intracorporeal medical devices, cyborgs are no longer exclusively a subject of science fiction novels, but technically they already exist in our society. In this review, we briefly summarize the development of modern prosthetics and the evolution of brain–machine interfaces, and discuss the latest technical developments of implantable devices, in particular, biocompatible integrated electronics and microfluidics used for communication and control of living organisms. Recent examples of animal cyborgs and their relevance to fundamental and applied biomedical research and bioethics in this novel and exciting field at the crossroads of chemistry, biomedicine, and the engineering sciences are presented.
Intestinal organoids recapitulate many features of the in vivo gastrointestinal tract and have revolutionized in vitro studies of intestinal function and disease. However, the restricted accessibility of the apical surface of the organoids facing the central lumen (apical-in) limits studies related to nutrient uptake and drug absorption and metabolism. Here, we demonstrate that pluripotent stem cell (PSC)-derived intestinal organoids with reversed epithelial polarity (apical-out) can successfully recapitulate tissue-specific functions. In particular, these apical-out organoids show strong epithelial barrier formation with all the major junctional complexes, nutrient transport and active lipid metabolism. Furthermore, the organoids express drug-metabolizing enzymes and relevant apical and basolateral transporters. The scalable and robust generation of functional, apical-out intestinal organoids lays the foundation for a completely new range of organoid-based high-throughput/high-content in vitro applications in the fields of nutrition, metabolism and drug discovery.
Research has shown that traditional dialysis is an insufficient long-term therapy for patients suffering from end-stage kidney disease due to the high retention of uremic toxins in the blood as a result of the absence of the active transport functionality of the proximal tubule (PT). The PT’s function is defined by the epithelial membrane transporters, which have an integral role in toxin clearance. However, the intricate PT transporter–toxin interactions are not fully explored, and it is challenging to decouple their effects in toxin removal in vitro. Computational models are necessary to unravel and quantify the toxin–transporter interactions and develop an alternative therapy to dialysis. This includes the bioartificial kidney, where the hollow dialysis fibers are covered with kidney epithelial cells. In this integrated experimental–computational study, we developed a PT computational model that focuses on indoxyl sulfate (IS) transport by organic anionic transporter 1 (OAT1), capturing the transporter density in detail along the basolateral cell membrane as well as the activity of the transporter and the inward boundary flux. The unknown parameter values of the OAT1 density (1.15×107 transporters µm−2), IS uptake (1.75×10−5 µM−1 s−1), and dissociation (4.18×10−4 s−1) were fitted and validated with experimental LC-MS/MS time-series data of the IS concentration. The computational model was expanded to incorporate albumin conformational changes present in uremic patients. The results suggest that IS removal in the physiological model was influenced mainly by transporter density and IS dissociation rate from OAT1 and not by the initial albumin concentration. While in uremic conditions considering albumin conformational changes, the rate-limiting factors were the transporter density and IS uptake rate, which were followed closely by the albumin-binding rate and IS dissociation rate. In summary, the results of this study provide an exciting avenue to help understand the toxin–transporter complexities in the PT and make better-informed decisions on bioartificial kidney designs and the underlining transporter-related issues in uremic patients.
Deposition of minerals, particularly calcium phosphates such as hydroxyapatite, is an important process in the formation of hard tissues such as bone. Herein, a new, affordable, straightforward and nondestructive method based on complex capacitance spectroscopy, an application of electrochemical impedance spectroscopy, is described which allows repeated and real‐time measurements of the same sample throughout the calcium phosphate deposition process. In contrast with end‐point assays which require large numbers of samples to obtain useful time‐course data, this method allows the kinetics of deposition to be measured using a single sample by measuring the impedance of a pair of interdigitated electrodes at a range of frequencies as the layer of mineral is deposited. Changes in the complex capacitance curve over time with deposition can be compared with images of the coating deposited on model substrates, and show different behavior depending on the composition of the coating and the conditions of deposition.
The self-assembly approach is a technically simple, rapid, and direct way to realize selective deposition of electrospun nanofibers. In the present study, we aimed to fabricate gradient polycaprolactone (PCL) honeycomb meshes by electrospinning. We demonstrated for the first time the ability to effectively fabricate a self-assembled gradient honeycomb pattern in electrospun meshes. Different honeycomb patterns were successfully fabricated by controlling the electrospinning conditions. The working distance was found to be the most important factor for the formation of gradient honeycomb structures. At a smaller working distance of 12 cm, gradients honeycomb patterns were successfully fabricated. The pore diameter of the obtained gradient honeycomb structures spanned a range from 800 μm to 300 μm. The average depth of gradient honeycomb was 123 ± 56 μm. These findings are interesting and particularly useful for us to optimize the design of gradients honeycomb scaffolds for interface tissue regeneration.
Multireplication Process In article 2300344, Rhiannon Grant, Stefan Giselbrecht and co-workers demonstrate a multireplication process that enables the faithful replication of electrospun fiber structures on various cell culture substrates. By decoupling fiber diameter, porosity, and material chemistry, this process allows for precise control over fiber morphology. This enables the engineering of well-defined cell microenvironments, facilitating the investigation of complex cell-material interactions.
Abstract Enthesitis, the inflammation of the enthesis, which is the point of attachment of tendons and ligaments to bones, is a common musculoskeletal disease. The inflammation often originates from the fibrocartilage region of the enthesis as a consequence of mechanical overuse or ‐load and consequently tissue damage. During enthesitis, waves of inflammatory cytokines propagate in(to) the fibrocartilage, resulting in detrimental, heterotopic bone formation. Understanding of human enthesitis and its treatment options is limited, also because of lacking in vitro model systems that can closely mimic the pathophysiology of the enthesis and can be used to develop therapies. In this study, an enthes(it)is‐on‐chip model is developed. On opposite sides of a porous culture membrane separating the chip's two microfluidic compartments, human mesenchymal stromal cells are selectively differentiated into tenocytes and fibrochondrocytes. By introducing an inflammatory cytokine cocktail into the fibrochondrocyte compartment, key aspects of acute and chronic enthesitis, measured as increased expression of inflammatory markers, can be recapitulated. Upon inducing chronic inflammatory conditions, hydroxyapatite deposition, enhanced osteogenic marker expression and reduced secretion of tissue‐related extracellular matrix components are observed. Adding the anti‐inflammatory drug celecoxib to the fibrochondrocyte compartment mitigates the inflammatory state, demonstrating the potential of the enthesitis‐on‐chip model for drug testing.
