Biomimetic electrospun tubular PLLA/gelatin nanofiber scaffold promoting regeneration of sciatic nerve transection in SD rat

The micro- or nanoscale surface morphology of the tissue engineering nerve guidance scaffold (NGS) will affect different cell behaviors, such as their growth rate, migration, and matrix secretion. Although different technologies for manufacturing scaffolds with biomimetic topography have been established, most of them tend to be high cost and long preparation time. Here we have prepared a biomimetic NGS with physical properties to simulate native nerve tissue more accurately. We used poly(l-lactic acid) (PLLA) nanofibers doped with gelatin to prepare a biomimetic NGS whose structure mimics the native epineurium layer. By adjusting the doping ratio of gelatin and PLLA in the tubular scaffold, the bionic scaffold's surface morphology and mechanical properties are closer to native tissues. In vitro cell scaffold interaction experiments demonstrated that the PLLA/gelatin nanofibers could significantly promote the elongation, proliferation, and the secretion of glial cell-derived neurotrophic factor (GDNF) of RSC96 Schwann cells (SCs), as well as the diffusion of GDNF. In vivo scaffold replacement of SD rat, sciatic nerves showed that the nerve guide scaffold composed of PLLA/gelatin nanofibers was helpful to the myelination of SCs and the remolding of epineurium in the injured area, which could effectively rehabilitate the motor and sensory functions of the injured nerve and prevent the atrophy of the target muscle tissue. This study showed that the synergistic impact of nano topographical and biochemical clues on designing biomimetic scaffolds could efficiently promote regenerating nerve tissue.