Biophysical Society Thematic Meeting | Riga 2026

Active and Responsive Soft Matter: From Biological to Engineered Systems

Friday Speaker Abstracts

BIOPHYSICAL APPROACHES TO REMODEL AND PERFUSE ORGANOID VASCULATURE Louis Paone 1 ; Adam Boberick 1 ; Olivia Barr 2 ; Tyler Lu 2 ; Raphael Lis 2 ; Peter Galie 1 ; 1 Rowan University, Biomedical Engineering, Glassboro, NJ, USA 2 Weill Cornell Medicine, New York, NY, USA The primary benefit of organoids is also one of their central caveats: allowing cells to develop their own organization and extracellular matrix architecture yields a more physiologically relevant model than microfluidic chip-based in vitro platforms but at the cost of controlling mechanical and biochemical stimuli experienced by the cells. Despite tremendous advances in the complexity of organoids, including the implementation of physiological vascular architectures, these models plateau in an immature state that does not accurately portray developed tissue systems. This limitation suggests that tuning the biophysical environment of the developing organoid may yield a strategy to advance its maturation. This presentation details approaches to use biophysical stimuli, specifically shear stress, to provide a level of control over organoid vascularization and maturity. Vascularized cerebral cortex organoids are cultured in a funnel-shaped hydrogel chamber that is functionalized with peptide motifs that facilitate attachment of the organoid to the wall, directing interstitial flow through the bulk of the matrix. After approximately one week in culture, the interstitial fluid flow causes vascular remodeling that results in intraluminal flow through the vasculature. Microparticle velocimetry measurements of > 1 mm/s and co-localization studies verify that fluorescent tracers traverse through the lumens of capillary-scale vessels rather than interstitially through the bulk, providing the first demonstration of controlled fluid flow through organoid vasculature. Cerebral cortex organoids produced from induced pluripotent stem cells with the “Arctic mutation”, a point mutation in the amyloid precursor protein (APP) gene, provide a means to model Alzheimer’s disease, which has a substantial vascular component to its pathology. Revertant and APP mutant organoids cultured in the intraluminal perfusion are used to interrogate transcriptional differences caused by the mutation, as measured by sequencing of mRNA isolated from revertant and mutant organoids. Future approaches to combine interstitial fluid flow with dynamic stiffening of the matrix may further control and advance organoid maturation and function.

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