Hyaluronic acid (HA)-based biomaterials have been demonstrated to promote wound healing and tissue regeneration, owing to the intrinsic and important role of HA in these processes. A deeper understanding of...

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Background There is great interest to engineer in vitro models that allow the study of complex biological processes of the microvasculature with high spatiotemporal resolution. Microfluidic systems are currently used to engineer microvasculature in vitro, which consists of perfusable microvascular networks (MVNs). These are formed through spontaneous vasculogenesis and exhibit the closest resemblance to physiological microvasculature. Unfortunately, under standard culture conditions and in the absence of co-culture with auxiliary cells as well as protease inhibitors, pure MVNs suffer from a short-lived stability. Methods Herein, we introduce a strategy for stabilization of MVNs through macromolecular crowding (MMC) based on a previously established mixture of Ficoll macromolecules. The biophysical principle of MMC is based on macromolecules occupying space, thus increasing the effective concentration of other components and thereby accelerating various biological processes, such as extracellular matrix deposition. We thus hypothesized that MMC will promote the accumulation of vascular ECM (basement membrane) components and lead to a stabilization of MVN with improved functionality. Results MMC promoted the enrichment of cellular junctions and basement membrane components, while reducing cellular contractility. The resulting advantageous balance of adhesive forces over cellular tension resulted in a significant stabilization of MVNs over time, as well as improved vascular barrier function, closely resembling that of in vivo microvasculature. Conclusion Application of MMC to MVNs in microfluidic devices provides a reliable, flexible and versatile approach to stabilize engineered microvessels under simulated physiological conditions.

BackgroundStudies on cognitive impairment in patients with past history of neuropsychiatric lupus (NPSLE) were often confounded by psychiatric and other disease related factors.ObjectivesThis study aims to evaluate cognitive function in NPSLE patients in relation to psychiatric factors longitudinally in comparison to matched controls.MethodsNPSLE patients and matched disease and healthy controls were examined by full battery of neurocognitive tests that covered 8 cognitive domains at 2 time-points 12 months apart. Depressive and anxiety symptoms were measured by HADS.Results18 NPSLE and 18 patients with systemic lupus erythematosus (SLE) who had no previous cerebral involvement (non-NPSLE) matched to age, sex and disease duration, and 16 age- and sex- matched healthy subjects were recruited. NPSLE patients consistently reported more cognitive symptoms and anxiety symptoms than non-NPSLE patients over both time-points. NPSLE patients had significantly worse simple and complex attention, memory, reasoning and visuospatial processing compared to non-NPSLE patients, among which memory and simple attention remained significantly impaired after adjustment to confounders. Anxiety and depressive symptoms were found to have an effect on raw scores but not demographically adjusted T score of neurocognitive tests. Unlike non-NPSLE subjects, NPSLE patients also failed to demonstrate practice effect upon re-evaluation over 12 months. Both NPSLE and non-NPSLE patients had worse memory than healthy subjects, with deficiency in more memory tests for NPSLE patients.ConclusionsNPSLE patients had significantly worse and persistently impaired cognitive functions involving memory, visuospatial processing and complex attention and impaired learning compared to non-NPSLE patients over 12-month re-assessment.Disclosure of InterestNone declared