Search bioRxiv⌕ Search

bioRxiv · 10.64898/2026.10.13.758926

Functional Performance of Electrospun Tissue-Engineered Heart Valve Scaffolds Across Geometries Under Aortic Conditions

Abstract

Electrospun, bioresorbable polymer scaffolds represent a compelling platform for tissue-engineered heart valves (TEHVs) owing to their fibrous microstructure, tunable mechanics and inherent capacity to support host-cell infiltration and remodeling. While recent in-vitro parametric studies of bioprosthetic heart valve (BHV) geometry have used silicone cast valves and Doppler echocardiography to link design parameters to hemodynamic performance and leaflet strain, the characterization of the functional behavior of electrospun whole-valve TEHV scaffolds across clinically relevant aortic conditions and across distinct leaflet geometries remains limited. Here, we present an end-to-end workflow in which polycaprolactone (PCL) is electrospun directly onto parametrized, 3D-printed mandrels derived from two established analytical leaflet geometry models, yielding 21 whole-valve scaffolds across five geometries without cutting or suturing of flat fiber sheets. Fiber diameter, orientation and scaffold porosity were assessed by scanning electron microscopy and confirmed to be consistent across scaffolds and geometries. A subset of 8 scaffolds were tested in a pulse duplicator under hypotensive, normotensive and hypertensive aortic conditions, achieving a mean geometric orifice area of 44.51% of the total valve area and demonstrating physiological opening and closing behavior throughout. These results emphasize electrospun whole-valve TEHVs as hemodynamically competent constructs at clinically relevant aortic conditions and provide a reproducible, geometry-driven fabrication and evaluation framework to further support their translation toward regenerative heart valve replacement.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Dillinger, H., Saberi, A., Manenti, M., Burgh-Vrees, I. v. d., Bouten, C.. 2026-10-14. Functional Performance of Electrospun Tissue-Engineered Heart Valve Scaffolds Across Geometries Under Aortic Conditions. https://doi.org/10.64898/2026.10.13.758926

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Mesoscale Soft Robotics for Mechanically Perturbing and Functionally Monitoring Responses in Human Organoids

Human organoids represent promising models for studies of significance to the biology and medical communities. Of the existing approaches for monitoring organoids, none offers the ability to apply programmable mechanical forces while simultaneously recording multi-modal physiological responses, of relevance to phenomena spanning from traumatic brain injuries to cardiac rhythm disorders. Here, we present a mesoscale soft robotic organoid interface that enables programmable delivery of forces to organoids of diverse shapes, and to map electrophysiological activity and mechanical responses. The platform combines actuation elements with integrated sensors for quantitative measurement and control. Studies using this technology reveal that spheroidal cortical organoids exhibit distinct responses to mechanical trauma, including silencing, recovery, and changes in neuronal firing patterns. Additional experiments on cardiac ring tissues demonstrate that sustained stretching induces beat-to-beat rhythm variability and altered conduction. The results establish a framework for investigating force-triggered transitions between physiological and disease-like states in human tissue models.

bioengineering↗

Few-shot regulatory sequence design with a genomic language model

A central challenge in generative biology is translating knowledge learned from natural sequences and experiments into designs with desired functions. In-context learning (ICL) is an emergent capability of large language models that allows them to adapt to new tasks from a few examples without additional training, enabling these models to become general-purpose learners. Here, we show that the genome language model, Evo 2, exhibits generative ICL in biological sequence design. Prompting with just tens of examples conditions Evo 2 to generate novel and diverse regulatory DNA sequences without any additional training. Mechanistic analysis suggests that genomic ICL may originate from induction, similar to phenomena observed in natural language. Reinforcement learning leveraging sequence-to-function models as experiment-derived rewards further strengthens ICL. We first validate this approach by generating enhancers that drive cell-type-specific gene expression in three human cell lines. Extending this approach in vivo, enhancers designed using human regulatory element data selectively label layer 5 extratelencephalic neurons in the mouse cortex with high specificity and stronger activity than existing enhancers. Our study provides evidence of emergent properties in genomic sequence models and introduces a promising approach for improving functional conditioning in generative biology.

bioengineering↗

IOP-independent treatment for neurodegeneration in glaucoma using optimized ROS-scavenging microparticles for sustained release of erythropoietin

Glaucoma is a slow-progressing neurodegenerative disease of the optic projection to the brain and a leading cause of blindness worldwide. Current treatments are targeted towards lowering intraocular pressure (IOP), the only known, modifiable risk factor; however, this strategy is ineffective in many patients. An early hallmark of glaucomatous neurodegeneration is increased reactive oxygen species (ROS), representing an alternative opportunity for intervention to halt or slow disease progression. In this work, we optimize a ROS-scavenging copolymer, poly(propylene sulfide-co-ethylene sulfide) (PPSES), for formulation of size-controlled, stabilized, antioxidant microparticles (MPs) for sustained release of the protein erythropoietin (EPO). EPO promotes biological antioxidant defense via activation of NRF2-mediated transcription of antioxidant genes. This MP system overcomes the short half-life of EPO and leverages the combined benefits of bioactive EPO with long-lasting, inherently antioxidant PPSES MPs. The lead EPO-MP formulation preserves neurons in both mouse and non-human primate models of glaucoma through suppression of oxidative stress and optic nerve degeneration. EPO-loaded PPSES MPs represent a translationally relevant therapy for long-term management of glaucoma independent of IOP.

bioengineering↗