PEER-REVIEWED PUBLICATION

2026

3D-printed scaffolds encapsulating red-blood-cell-derived extracellular vesicles for microRNA delivery

Huang C, Jayasinghe MK, et al.

Cell Biomaterials

Nanyang Technological University, National University of Singapore, University of Sydney, National Neuroscience Institute

Australia, Singapore

RESEARCH SUMMARY

This study developed a localized RNA delivery platform that combined red-blood-cell-derived extracellular vesicles with DLP 3D-printed GelMA/PEGDA scaffolds for spinal cord injury repair. RBCEVs showed strong cytocompatibility in primary CNS cells and cell-type-specific uptake, with the highest internalization and gene-silencing efficiency in oligodendrocyte precursor cells, where uptake exceeded 70% and gene silencing reached 74.2%. Embedding RBCEVs into printed microchannel scaffolds enabled sustained release of miR-219 and miR-338 for more than 21 days while preserving vesicle structure and bioactivity. In vitro, this system promoted OPC differentiation, increased MBP-positive mature oligodendrocytes, and enhanced myelination. In a rat complete transection spinal cord injury model, scaffold-mediated delivery increased CC1-positive mature oligodendrocytes, reduced PDGFRα-positive OPCs, and shifted microglia toward a more anti-inflammatory phenotype, supporting scaffold-based RBCEV delivery as a promising regenerative strategy for CNS remyelination.

A CellScale MicroTester was used to measure the stiffness of DLP-printed GelMA/PEGDA scaffolds with and without encapsulated red-blood-cell-derived extracellular vesicles. After printing and washing, scaffold stiffness was quantified from the linear region of force-displacement curves using a 0.5588 mm beam at a displacement rate of 2 μm/s, with stiffness calculated at 100 μm displacement corresponding to 5% strain. The MicroTester data showed that incorporation of RBCEVs significantly reduced scaffold stiffness relative to bare scaffolds. These measurements were important for confirming how EV loading altered the mechanical behavior of the printed delivery matrix and for linking scaffold design, release behavior, and regenerative performance in the spinal cord injury model.

AUTHORS

Chongquan Huang, Migara Kavishka Jayasinghe, Vaibavi Ramanujam, Kieran Lau, Minh Thi Nguyet Le, Sing Yian Chew.

PUBLICATION DETAILS

JOURNAL

Cell Biomaterials

YEAR

2026

INSTITUTIONS

Nanyang Technological University, National University of Singapore, University of Sydney, National Neuroscience Institute

COUNTRIES

Australia, Singapore

INSTRUMENT USED

MicroTester

TESTING METHODS

Compression TestingMicro-Mechanical Testing

RESEARCH APPLICATIONS

3D Bioprinting & Bioink Materials TestingDrug Screening & Drug Delivery MechanicsNeural Tissue & CNS MechanicsScaffold Mechanical Testing

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