Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.02.02.636143

Evaluating Flow-Focused Microfluidic Device Fabrication Techniques for Silk Fibroin Microgel Production

Haghighattalab, M.·Karimi, F.·Farbehi, N.·Rnjak-Kovacina, J.
View original source ↗Export metadata ↓

Abstract

Microgels, or micro-scale hydrogels, are versatile emerging biomaterials. They absorb large amounts of water and facilitate molecule transfer. Their tunable size and shape and the capacity to form 3D scaffolds with microscale porosity offer significant advantages over traditional bulk hydrogels. Various strategies exist for fabricating microgels with microfluidic techniques offering the most control of microgel properties. This study compares three microfluidic device fabrication techniques--maskless photolithography, laser engraving, and 3D printing--for making photo-crosslinked silk fibroin microgels. Silk microgels were fabricated via water-in-oil microfluidics and crosslinked through di-tyrosine bonds between native tyrosine residues in silk. Microfluidic devices with target channel depths of 50, 100, or 400 {micro}m were successfully fabricated, with each technique offering unique advantages and limitations. Maskless photolithography provided the highest channel patterning accuracy and smoothest profiles but was costly and required specialized facilities. Laser engraving was affordable but labor-intensive, with lower accuracy in the X-Y plane for deeper channels. 3D printing was user-friendly and affordable but resulted in low accuracy for 50 {micro}m channels and rougher channel profiles, leading to larger microgels and less efficient microgel formation than the other techniques. Spherical silk microgels with diameters between 50 {micro}m and > 400 {micro}m were produced by modulating channel depth and flow rates, while rod-shaped microgels were made by crosslinking in the outlet tubing. Silk molecular weight was adjusted to control surface porosity and compressive modulus, with lower molecular weight silk resulting in higher porosity and softer microgels (modulated between [~] 40 kPa and [~] 590 kPa) while maintaining consistent size. This study demonstrates the versatility and effectiveness of different microfluidic device fabrication techniques for producing photo-crosslinked silk microgels with tunable properties for biomedical applications.

Source connections

Explore related subjects

bioengineeringPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Haghighattalab, M., Karimi, F., Farbehi, N., Rnjak-Kovacina, J.. 2025-02-07. Evaluating Flow-Focused Microfluidic Device Fabrication Techniques for Silk Fibroin Microgel Production. https://doi.org/10.1101/2025.02.02.636143

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

KEEP EXPLORING

Related preprints

bioRxiv2026

Synergy-informed bilevel optimization reveals joint-specific benefits for realistic exoskeleton torque prediction

Simulation-driven optimization can guide exoskeleton control design, but its utility is limited by the accuracy with which muscle coordination is predicted. Strict effort-minimization formulations predict non-physiological muscle shutdown under high exoskeleton assistance, leading to peak assistive torques that exceed values reported in human-in-the-loop experiments. We evaluated the accuracy of synergy-informed simulations at predicting assistance across four single-joint exoskeleton configurations: ankle plantarflexion, knee extension, hip flexion, and hip abduction. We implemented a bilevel optimization to predict a parameterized assistive torque that minimizes metabolic cost, with assisted muscle dynamics estimated via either effort-minimization simulations (minimizing muscle effort only) or synergy-informed simulations (minimizing muscle effort constrained to a synergy structure). We used experimental data from five unimpaired adults walking at their preferred speed and compared results descriptively between the two formulations within each subject. Assistance based on effort-minimization simulations shut down agonist muscle activations and overestimated peak assistive torque compared with experimental values. In contrast, constraining muscle controls to a synergy structure prevented non-physiological muscle shutdown and yielded assistive torques closer to those measured in human-in-the-loop experiments. This benefit was not observed equally across all assisted degrees of freedom or subjects, emerging only where no single synergy could be suppressed to unload the assisted muscles. Synergy weights can therefore be interpreted as joint-specific predictors of when simulations can reliably inform wearable robot design.

bioengineering↗
bioRxiv2026

Engineered microvessel networks -- Longitudinal transcriptomic profiling validates chip-grown tissues as a robust model for studying vasculature

Vascularised Organ-on-Chip (OoC) models are promising New Approach Methodologies (NAMs), but their translation requires validation for defined Contexts of Use (CoU). Here, we combine microfluidic microvessel networks (MVNs) with longitudinal bulk and single-cell RNA sequencing to determine how cell provenance influences engineered vascular phenotype. Stromal cell identity produced distinct network architectures and transcriptional trajectories, demonstrating that support cells, commonly treated as interchangeable, represent an important CoU variable. Primary human pancreatic microvascular endothelial cells failed to form stable perfusable networks, but supplementation with 10% Human Umbilical Vein Endothelial Cells (HUVECs) or Blood Outgrowth Endothelial Cells (BOECs) rescued self-assembly. Single-cell transcriptomics identified specialised endothelial populations associated with vascular morphogenesis, including tip, stalk, phalanx, endothelial to mesenchymal transition (EndMT) and pericyte-like endothelial cells. Failed networks lacked coherent endothelial specialisation, whereas rescued networks restored stabilising cell states and revealed FLRT2--UNC5B signalling within pericyte-like HUVECs, recapitulating a pathway implicated in angiogenic development in vivo. These findings establish cell provenance as a critical determinant of microvascular NAM performance and demonstrate how transcriptomic validation can define and strengthen the biological relevance of microvessel-on-chip models for specific CoUs.

bioengineering↗
bioRxiv2026

Benchmarking foundation models for resting-state functional magnetic resonance imaging time series in cognitive aging research

Foundation models trained on large neuroimaging datasets could help smaller studies investigate cognition from brain recordings. However, whether the foundation model-derived representations improve assessment of current cognition, prediction of follow-up cognition, or characterization of cognitive change remains unclear. We evaluated nine configurations from five model families that process regional resting-state functional magnetic resonance imaging time series, using 3,103 scans from 1,653 participants across two observational and five intervention aging cohorts. Primary frozen representations showed no consistent superiority over conventional functional connectivity for concurrent cognitive associations or diagnostic classification. Changing the readout improved selected concurrent cognitive associations without updating model weights, indicating that performance depended partly on how representations were extracted. Additional post-training and embedding alignment yielded gains in selected settings but did not consistently improve performance across outcomes. In the primary longitudinal analyses, imaging representations did not establish added value beyond baseline clinical measures. These findings show that readout choice influences concurrent cognitive associations, while the added value of these representations for longitudinal outcomes remains unestablished.

bioengineering↗