Summary: Spinal cord injuries have long been seen as permanent because neurons in the central nervous system do not naturally regenerate. Researchers at RCSI University of Medicine and Health Sciences have developed a novel 3D-printed implant that could change that outlook by combining a biomimetic scaffold with RNA-loaded nanoparticles to encourage nerve regrowth.
The research presents a multifunctional scaffold that mimics the spinal cord’s anatomy and stiffness while delivering small interfering RNA (siRNA) particles that silence the PTEN gene—a molecular brake that limits neuronal regeneration. By pairing physical support with a targeted biological signal, the implant greatly enhanced axonal growth in laboratory models, offering a promising avenue for restoring connections lost after spinal cord injury.
Key Facts
- Dual-action design: The implant provides a three-dimensional structure for cells to attach and grow while releasing siRNA to modify cell behavior.
- Targeting PTEN: The delivered siRNA specifically reduces PTEN expression, removing an internal barrier that suppresses the regenerative capacity of adult neurons.
- Biomimetic scaffold: The 3D-printed structure is engineered to match the mechanical stiffness and anatomical architecture of spinal cord tissue to promote integration and avoid further damage.
- Enhanced nerve regrowth: In laboratory models, neurons exposed to the RNA-activated scaffold showed significantly increased neurite extension across the injury site.
- Patient-centered development: The project involved input from an advisory panel supported by the Irish Rugby Football Union Charitable Trust to ensure the research addresses clinical priorities and the needs of people living with spinal cord injury.
Source: RCSI
Overview
Researchers from RCSI’s Tissue Engineering Research Group (TERG) and the Research Ireland Centre for Advanced Materials and BioEngineering Research (AMBER) led the study. Published in the journal Bioactive Materials, the work demonstrates how a 3D scaffold, carefully tuned to resemble spinal cord tissue, can be combined with engineered nanoparticles to deliver siRNA directly to injured neurons and encourage axonal regrowth.
Spinal cord injuries often lead to lasting paralysis because central nervous system neurons have a limited ability to regrow. Biomaterial scaffolds alone can provide physical guidance at the lesion, but molecular inhibitors—like PTEN—still prevent effective regeneration. This study addresses both barriers at once by combining structural guidance with local delivery of RNA therapeutics to reawaken neuronal growth programs.
The team formulated siRNA into nanoparticles using a non-viral glycosaminoglycan-binding enhanced transduction (GET) peptide vector. These GET-siRNA nanoparticles were able to transfect primary neurons, a cell type that is typically hard to manipulate, and then were incorporated into a hyaluronic acid scaffold enriched with neurotrophic components such as collagen IV and fibronectin. The resulting PTEN-siRNA-activated scaffold significantly improved neurite outgrowth in vitro.
“We’ve created an environment that both physically and biologically re‑enhances the regenerative capacity of injured neurons, which is a key requirement for restoring function after spinal cord injury,” said Professor Fergal O’Brien, Deputy Vice-Chancellor for Research and Innovation, Professor of Bioengineering and Regenerative Medicine and Head of RCSI TERG. “In laboratory models of spinal cord injury, neurons exposed to the RNA-activated implant showed significantly enhanced growth.”
The research was guided by an advisory panel involving people living with spinal cord injury, clinicians, neuroscientists and engineers. This patient-centred approach, supported by the Irish Rugby Football Union Charitable Trust (IRFU-CT), helped shape priorities and ensure the work remains clinically relevant.
Dr Tara McGuire, who conducted the work as a PhD student in TERG, emphasized that while results in laboratory models are encouraging, the next step is in vivo testing to determine whether an RNA-activated biomaterial can bridge damaged spinal cord tissue and restore functional connections in living subjects.
Funding: The study received support from the Irish Rugby Football Union Charitable Trust and Research Ireland, with additional funding from the Anatomical Society and the Health Research Board.
Key Questions Answered
A: The central nervous system contains molecular “brakes” such as PTEN that suppress neuron growth in adulthood. These mechanisms help maintain stable neural circuits but limit recovery after injury.
A: The implant delivers siRNA that instructs cells to reduce production of the PTEN protein. With less PTEN present, neurons can reactivate intrinsic growth programs and extend axons toward their targets.
A: Not yet. The findings are from laboratory models. Planned in vivo studies will test whether RNA-activated biomaterials can restore movement and sensation in living organisms and inform future clinical development.
Editorial Notes
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full.
- Additional context was added by editorial staff to clarify the research and its implications.
About this spinal cord injury and neurotechnology research news
Author: Laura Anderson
Source: RCSI
Contact: Laura Anderson – RCSI
Image: The image is credited to Neuroscience News
Original Research: Open access. “Development of a PTEN-siRNA activated scaffold to promote axonal regrowth following spinal cord injury” by Tara K. McGuire, Martyna Stasiewicz, Cian O’Connor, Ian Woods, Jack Maughan, Marko Dobricic, Giulio Brunetti, James E. Dixon, Adrian G. Dervan, and Fergal J. O’Brien. Bioactive Materials. DOI: 10.1016/j.bioactmat.2026.01.022
Abstract
Development of a PTEN-siRNA activated scaffold to promote axonal regrowth following spinal cord injury
This study reports the development of a PTEN-siRNA activated scaffold designed for spinal cord injury repair. siRNA was combined with a non-viral glycosaminoglycan-binding enhanced transduction (GET) peptide vector to form nanoparticles capable of transfecting primary neurons. These GET-siRNA nanoparticles were incorporated into a hyaluronic acid scaffold enriched with neurotrophic extracellular matrix proteins such as collagen IV and fibronectin. Functionalising the scaffold with PTEN-siRNA nanoparticles significantly increased its ability to promote neurite outgrowth, supporting its potential as a combined structural and molecular strategy for enhancing neural regeneration after spinal cord injury.