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Bicontinuous Microarchitected Scaffolds Provide Topographic Cues That Govern Neuronal Behavior and Maturation

  • Prince D. Okoro
  • , Kevin Dalsania
  • , Shiril B. Iragavarapu
  • , Benjamin Dela Cruz
  • , Aihik Banerjee
  • , Merve Basaranbilek
  • , Martin F. Haase
  • , Bahman Anvari
  • , Iman Noshadi*
  • *Corresponding author for this work
  • University of California at Irvine

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

3D tissue-engineered models hold great promise for recreating the intricate architecture and dynamic functions of neural tissues. However, replicating the nuanced structural cues of the brain in vitro remains challenging, as existing platforms often fail to capture the precise architectural motifs that regulate biological responses. Here, a bicontinuous interfacially jammed emulsion gel (bijel)-based fabrication strategy that combines solvent transfer-induced phase separation (STrIPS), microfluidics, and bioprinting to develop a Bijel-Integrated PORous Engineered System (BIPORES) for neural tissue engineering is introduced. This multifaceted approach yields scaffolds featuring interconnected micropores and textured surfaces interspersed with a hyperbolic curvature, seamlessly integrated within macroscale fibrous networks. By leveraging STrIPS of a ternary precursor mixture stabilized by amphiphilic nanoparticles, we synthesized poly(ethylene glycol) diacrylate (PEGDA) BIPORES support neural stem cell adhesion within 30 s without additional biological factors-a first for PEGDA scaffolds. Long-term cultures demonstrate extensive migration, robust proliferation, and differentiation into neuronal and astrocytic lineages, forming 3D networks with enhanced synaptic activity. Collagen encapsulation amplifies 3D cell growth, simulating native neuroanatomical compartmentalization. From a biomimicry standpoint, this multiscale fabrication strategy better approximates native neural tissue dynamics with significant implications for disease modeling, drug screening, and regenerative therapies.
Original languageEnglish
Article numbere09452
Number of pages16
JournalAdvanced Functional Materials
Volume36
Issue number5
Early online date1 Oct 2025
DOIs
Publication statusPublished - 15 Jan 2026

Bibliographical note

Publisher Copyright:
© 2025 The Author(s). Advanced Functional Materials published by Wiley-VCH GmbH.

Funding

The authors gratefully acknowledge financial support from the UCR startup fund (F0432627). P.D.O. was supported by a TRANSCEND fellowship from the California Institute of Regenerative Medicine (Award No. EDUC4‐12752). The contents of this publication are solely the responsibility of the authors and do not necessarily represent official views of CIRM or other agencies of the State of California.

FundersFunder number
UCR startup fundF0432627
California Institute of Regenerative MedicineEDUC4‐12752

    Keywords

    • 3D neural tissue engineering
    • Bicontinuous scaffolds
    • Bioactive materials
    • Hierarchical microarchitectures
    • In vitro tissue models
    • Neural stem cells

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