Biology subjects

Rodriguez-Cabello, J. C.

Publications and source records attributed to Rodriguez-Cabello, J. C..

3 recordsLinked to original sources

bioRxiv2026

A Micro-Patterned, hiPSC-Derived Vascular Graft with Enhanced Endothelialization via Shear Redistribution

Small-diameter vascular grafts that can grow with pediatric patients and resist thrombosis remain an unmet need, primarily due to slow and unstable endothelialization. Here, we engineer a tri-layer, human induced pluripotent stem cell (hiPSC)-derived vascular graft featuring a soft, patterned lumen. We introduce a scalable soft-lithography method to imprint longitudinal micro-grooves directly into the lumen of compliant hydrogel tubes, a key advance for cell-laden constructs. Computational fluid dynamics reveals that these grooves redistribute wall shear stress into protective low-shear valleys and aligning high-shear ridges without increasing the mean load. This engineered shear landscape, combined with a bioactive elastin-like recombinamer (ELR) hydrogel matrix, synergistically enhances hiPSC-endothelial cell (hiPSC-EC) capture and retention under perfusion. Patterned grafts accelerate the formation of confluent, axially aligned endothelial monolayers with mature VE-cadherin junctions, outperforming non-patterned controls. Concurrently, smooth muscle cells within the graft wall deposit extracellular matrix, driving time-dependent mechanical maturation. This platform provides a physiologically relevant model for vascular disease and a promising strategy for engineering growth-competent pediatric grafts.

bioengineering↗

bioRxiv2026

Patterned ELR-Gelatin Hydrogels Enable Rapid Endothelial Monolayer Formation via Bioactive Matrix Chemistry and Surface Topography

The endothelialization of organ-on-chip platforms and vascular implants is often limited by slow cell attachment and unstable monolayer formation. This work presents a scalable workflow that imprints micro- and nano-gratings into elastin-like recombinamer (ELR)-based hydrogels, enabling rapid endothelial cell capture and accelerating monolayer formation within 14 days. Three gelatin-ELR formulations are engineered, with {superscript 1}H-NMR confirming incorporation of sequences designed to modulate bioactivity (ELR1: inert; ELR2: uPA-responsive; ELR3: RGD-adhesive). ELR incorporation generates fibrillar microstructures and enhances mechanical performance, yielding elastic-dominant networks suitable for high-fidelity pattern transfer and stable culture. Using this library, the combined effects of ELR bioactivity and groove geometry on human iPSC-derived endothelial cells (iPSC-ECs) are systematically evaluated. In a 15-minute attachment assay, patterned ELR composites markedly improve cell retention compared to gelatin, with ELR2 on [~]350 nm and [~]4 {micro}m grooves performing best, consistent with controlled, cell-mediated interfacial remodeling. This early advantage persists, as ELR2 and ELR3 hydrogels support rapid alignment and reach confluence by day 14, whereas gelatin remains sub-confluent. Cytoskeletal analysis confirms F-actin alignment. By combining enhanced early capture with protease-regulated remodeling, ELR2 identifies a favorable design window. These results establish a materials design framework linking programmable ELR chemistry with surface topography to engineer endothelial interfaces, providing a versatile platform for vascular biomaterials and microphysiological systems.

bioengineering↗

bioRxiv2025

Topology-Encoded Polarity in Oppositely Charged Binary IDPP Condensates: Multiphase Organization from Non-Coacervating Partners as a Minimal Model of Complex Coacervation

Synthetic condensates provide a way to engineer compartmentalized microenvironments that mimic the properties and functions of natural ones, yet the principles that govern their phase behavior and internal organization remain incompletely defined. Introducing charged residues into intrinsically disordered protein polymers (IDPPs) with LCST phase behavior typically suppresses phase separation under physiological conditions. Here we show that pairing two such oppositely charged IDPPs restores and programs LCST-driven liquid-liquid phase separation (LLPS), enabling a minimalist two-component platform for constructing synthetic condensates whose formation, size, and internal organization are encoded directly in sequence. LLPS emerges from an asymmetric, entropy-driven interplay between hydrophobic collapse, solvent reorganization, and salt-bridge topology. The balance between inter- and intrachain ionic pairing leads to distinct dense-phase microenvironments with tunable residual charge and micropolarity, thereby controlling condensate formation, and miscibility and the emergence of single-phase or multiphase protein condensates. The condensate interior further alters the ionization thermodynamics of charged residues shifting their apparent pKa and enabling tunable pH responses. Systems dominated by interchain salt bridges form low-polarity condensates that mix uniformly with hydrophobic partners, whereas molecular architectures favoring intrachain pairing retain residual charge and, in the presence of hydrophobic partners, undergo spontaneous internal demixing into multiphase assemblies. These findings establish a mechanistic, sequence-level framework for encoding phase behavior, micropolarity, and mesoscale organization in synthetic condensates, and demonstrate how minimalistic LCST-IDPP pairs can be engineered to create programmable microenvironments, opening avenues toward engineered condensates with higher-order organization and adaptive capabilities.

biophysics↗