Organ-on-chip (OOC) systems are revolutionizing tissue engineering by providing dynamic models of tissue structure, organ-level function, and disease phenotypes using human cells. However, nonbiological components of OOC devices often limit the recapitulation of in vivo–like tissue-tissue cross-talk and morphogenesis. Here, we engineered a kidney glomerulus-on-a-chip that recapitulates glomerular morphogenesis and barrier function using a biomimetic ultrathin membrane and human-induced pluripotent stem cells. The resulting chip comprised a proximate epithelial-endothelial tissue interface, which reconstituted the selective molecular filtration function of healthy and diseased kidneys. In addition, fenestrated endothelium was successfully induced from human pluripotent stem cells in an OOC device, through in vivo–like paracrine signaling across the ultrathin membrane. Thus, this device provides a dynamic tissue engineering platform for modeling human kidney–specific morphogenesis and function, enabling mechanistic studies of stem cell differentiation, organ physiology, and pathophysiology.

Heparan sulfate proteoglycans (HSPGs) have been recognized as key plasma membrane-tethered co-receptors for a broad range of growth factors and cytokines containing cationic heparan-binding domains^1,2. However, how HSPGs mechanistically mediate signalling at the cell surface—particularly in the context of cell surface RNA—remain poorly understood. During developmental and disease processes, vascular endothelial growth factor (VEGF-A), a heparan sulfate-binding factor, regulates endothelial cell growth and angiogenesis³. The regulatory paradigm for endothelial cell-mediated selectively of VEGF-A binding and activity has largely been focused on understanding the selective sulfation of the anionic heparan sulfate chains^4,5,6,7,8. Here we examine the organizational rules of a new class of anionic cell surface conjugates, glycoRNAs^9,10, and cell surface RNA-binding proteins (csRBPs^11,12). Leveraging genome-scale knockout screens, we discovered that heparan sulfate biosynthesis and specifically the 6-O-sulfated forms of heparan sulfate chains are critical for the assembly of clusters of glycoRNAs and csRBPs (cell surface ribonucleoproteins (csRNPs)). Mechanistically, we show that these clusters antagonize heparan sulfate-mediated activation of ERK signalling downstream of VEGF-A. We demonstrate that the heparan sulfate-binding domain of VEGF-A₁₆₅ is responsible for binding RNA, and that disrupting this interaction enhances ERK signalling and impairs vascular development both in vitro and in vivo and is conserved across species. Our study thus uncovers a previously unrecognized regulatory axis by which csRNPs negatively modulate heparan sulfate-mediated signalling in the context of angiogenesis driven by VEGF-A.

Podocytes derived from human induced pluripotent stem (hiPS) cells are enabling studies of kidney development and disease. However, many of these studies are carried out in traditional tissue culture plates that do not accurately recapitulate the molecular and mechanical features necessary for modeling tissue- and organ-level functionalities. Overcoming these limitations requires the design and application of tunable biomaterial scaffolds. Silk fibroin is an attractive biomaterial due to its biocompatibility and versatility, which include its ability to form hydrogels, sponge-like scaffolds, and electrospun fibers and membranes appropriate for tissue engineering and biomedical applications. In this study, we show that hiPS cells can be differentiated into post-mitotic kidney glomerular podocytes on electrospun silk fibroin membranes functionalized with laminin. The resulting podocytes remain viable and express high levels of podocyte-specific markers consistent with the mature cellular phenotype. The resulting podocytes were propagated for at least two weeks, enabling secondary cell-based applications and analyses. This study demonstrates for the first time that electrospun silk fibroin membrane can serve as a supportive biocompatible platform for human podocyte differentiation and propagation. We anticipate that the results of this study will pave the way for the use of electrospun membranes and other biomimetic scaffolds for kidney tissue engineering, including the development of co-culture systems and organs-on-chips microphysiological devices.

TapeTech is a flexible, adhesive-based microfluidic connectivity solution that streamlines fluidic integration with organ-on-a-chip devices by providing leak-proof sealing, mitigating pressure surges, and enabling rapid, cost-effective customization.

Purpose: Long-term oxygen therapy involves utilizing stationary oxygen concentrators to allow patients with respiratory illnesses to attain sufficient blood oxygenation via supplemental oxygen. Disadvantages of these devices include their lack of remote adjustability and domiciliary accessibility. To adjust oxygen flow, patients typically walk across their homes – a physically taxing activity – to manually rotate the knob of the concentrator flowmeter. The purpose of this investigation was to develop a control system device that allows patients to remotely adjust the oxygen flow rates on their stationary oxygen concentrator. Methods: The engineering design process was used to develop the novel FLO2 device. The two-part system is composed of 1) a smartphone application and 2) an adjustable concentrator attachment unit that mechanically interfaces with the stationary oxygen concentrator flowmeter. Results: Product testing indicates that users successfully communicated to the concentrator attachment from a maximum distance of 41m in an open field, suggesting usability from anywhere inside a standard home. The calibration algorithm adjusted oxygen flow rates with an accuracy of ± 0.019 LPM and a precision of ± 0.042 LPM. Conclusion: Initial design testing suggests the device as a reliable and accurate method of wirelessly adjusting oxygen flow on a stationary oxygen concentrator, but further testing should be performed on different stationary oxygen concentrator models.