An injectable anisotropic alginate hydrogel containing oriented fibers for nerve tissue engineering

Abstract

There is a growing research interest on designing a tissue regenerative matrix that can be injected and forms an anisotropic network for effective nerve injury repair. Here, an injectable alginate hydrogel composed of magnetic polycaprolactone (PCL) short nanofibers were fabricated. Nanocomposite PCL centrifugal spun fibers containing superparamagnetic iron oxide nanoparticles (SPIONs) were cut into short nanofibers (SFs) through micro-cutting technique and subsequently incorporated into alginate hydrogels. Doping SPION into short PCL fibers allows the SFs alignment by external magnetic fields in the millitesla (mT) order within the hydrogel. The effect of SFs lengths (5, 25 and 50 µm) as well as magnetic short fibers (M.SFs) concentration (0.5, 1, 2.5, 5 and 10 mg / ml) inside alginate hydrogel on fiber orientation under external magnetic field were investigated by measuring angular deflection of nanofibers. The results revealed that 5 and 25 µm M.SFs with 5 mg/ml concentration have the lowest angular deflection of 1.1⁰ and 6.8⁰, respectively. The mechanical properties of prepared hydrogels revealed that both oriented 5 and 25 µm M.SFs, have higher storage modulus (G’) and loss modulus (G”) values than the random ones and by increasing M.SFs length from 5 µm to 25 µm, G’ and G” values displayed descending trend. The fluorescence microscopy of olfactory ecto-mesenchymal stem cells (OE-MSCs) encapsulated in hybrid hydrogels containing oriented M.SFs showed the possibility of preserving cell viability after 7 days. Following 14-day of induction, the oriented 25 µm M.SF led to the acceleration of neural differentiation of OE-MSCs versus the random one. Therefore, it was expected that ordered injectable alginate/M.SFs hybrid hydrogels function as a minimal invasive constructs for the regeneration of neural tissues.