One of the structurally more attractive features of nanofiber scaffolds is their three-dimensional architecture. Because they are thought to more closely mimic the size and environment of the natural extracellular matrix in the body, they continue to be studied not only as cell support scaffolds, but, a new study has shown, robust drug and gene delivery vehicles.
Moreover, the platform employs two component scaffolds, which have been enjoying increased attention in recent years, to achieve differential physical and delivery characteristics.
Nguyen et al. recently reported the development of biodegradable, three-dimensional aligned nanofibers-hydrogel scaffolds for sustained drug and gene delivery, with neuronal regeneration after spinal cord injury being the therapeutic model system used. The scaffolds are comprised of aligned poly(ε-caprolactone-co-ethyl ethylene phosphate) (PCLEEP) electrospun nanofibers distributed within a collagen hydrogel.
The work comes from the lab of Sing Yian Chew at Nanyang Technological University in Singapore and is published in Scientific Reports.
A digaram showing the scaffold fabrication process is shown below. Drugs are encapsulated wither into the electrospun nanofibers or within the collagen hydrogel component before the two components are combined.
The authors used neurotrophin-3 (NT-3) as the model protein and miR-222 as the model microRNA, encapsulating both within the scaffold to generate a biofunctionalized structure that can impart axonal sprouting and regeneration (from NT-3) and neuronal growth (from miR-222). The structural architecture of the nanofibers also promotes guidance for neuronal regeneration, important for neuronal healing after spinal cord injury.
In vitro, the scaffold showed 51.6% degradation after 3 months. The in vivo release of NT-3 followed initial burst kinetics, with 90.3% released within the first week, and the release continued steadily for up to 3 months (99.7 ± 0.07%). For miRNA, the release was 27.1 ± 3.38% within the first week, and continued steadily for about 2 months. This resulted in the presence of aligned regenerated axons throughout the implant as early as one week post-implantation. Gene delivery was also confirmed by encapsulating double stranded oligonucleotides within the scaffold.
Functionally, the implanted scaffold demonstrated myelin-associated glycoprotein, a marker of oligodendrocyte myelination, throughout the scaffolds at 4 weeks post-implantation, co-localized with NF + axons, while miR-222 was shown to support robust neurite ingrowth 20 days post implantation.
Because the scaffold is composed of two compositionally different moieties – a nanofiber component and a hydrogel – multiple therapeutic molecules can be incorporated within different regions of the scaffold, providing the potential for differential release patterns.
As with all studies,