Development of a PTEN-siRNA activated scaffold to promote axonal regrowth following spinal cord injury

This study showcases the successful development of a PTEN -siRNA activated scaffold for SCI repair applications. Initially, siRNA was combined with the novel non-viral glycosaminoglycan-binding enhanced transduction (GET) peptide vector (image of GET vector from [22]). The formulated GET-siRNA nanoparticles effectively transfected primary neurons, a cell type generally considered challenging to transfect. Subsequently, siRNA-nanoparticles were incorporated into a hyaluronic acid scaffold enriched with neurotrophic extracellular matrix proteins (collagen IV and fibronectin) developed by our laboratory for spinal cord repair applications. Functionalisation of these scaffolds with PTEN -siRNA nanoparticles significantly enhanced their capacity to promote neurite outgrowth. • An siRNA-scaffold targeting phosphatase and tensin homolog (PTEN) was developed for spinal cord injury (SCI) applications. • Glycosaminoglycan (GAG)-binding enhanced transduction (GET) peptide vectors successfully delivered siRNA into neurons. • Incorporation of PTEN-siRNA nanoparticles into a SCI-scaffold designed to mimic native spinal cord enhanced neuronal growth. • The siRNA-activated scaffold was capable of effectively delivering siRNA-nanoparticles into complex neural tissue. • siRNA-scaffolds may act as a reservoir of siRNA-nanoparticles and a trophic environment for growth in future in vivo studies.