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Biology subjects

Richter, Y.

Publications and source records attributed to Richter, Y..

3 recordsLinked to original sources

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↗

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↗

3D Bioprinted Cell-laden GrooveNeuroTube: A Multifunctional Platform for Ex Vivo Neural Cell Migration and Growth Studies

Extensive peripheral nerve injuries often lead to the loss of neurological function due to slow regeneration and limited recovery over large gaps. Current clinical interventions, such as nerve guidance conduits (NGCs), face challenges in creating biomimetic microenvironments that effectively support nerve repair. The developed GrooveNeuroTube is composed of hyaluronic acid methacrylate and gelatin methacrylate hydrogel, incorporating active agents (growth factors and antibacterial agents) encapsulated within an NGC conduit made of 3D-printed PCL grid fibers. In vitro studies showed that GrooveNeuroTube significantly promoted migration of dorsal root ganglion (DRG) neuronal cells, 3D bioprinted at the far ends of the conduit to imitate a proximal nerve injury as a novel ex vivo model. A long-term culture of up to 60 days was employed to better mimic in vivo conditions. This model tested the effects of pulsed electromagnetic field (PEMF) stimulation on neural tissue development. After 60 days, GrooveNeuroTube showed a 32% cell migration increase compared to the growth-factor-group and 105% compared to the no-growth-factor condition. These results confirm that the GrooveNeuroTube system can effectively support sustained neural cell migration and maturation over extended periods, proving a new technology for testing peripheral nerve injury ex vivo. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/639097v2_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@14c7799org.highwire.dtl.DTLVardef@14011c3org.highwire.dtl.DTLVardef@14e5a79org.highwire.dtl.DTLVardef@115e281_HPS_FORMAT_FIGEXP M_FIG C_FIG The graphical abstract was created with BioRender.com.

bioengineering↗