Abstract
Purpose:
To provide a more permissive environment for axonal regeneration following injury to optic nerve.Regeneration of the CNS in mammals is very limited due to physical and chemical inhibitors and barriers that react following optic nerve asault and the absence of positive cues that elicit and guide repair.Hydrogels are considered to be good materials that support CNS repair due to high oxygen and nutrient permeabiltyand low interface tensions.Hyaluronic acid (HA) is a natural organic polymer used as a buliding block for hydrogel formation.It is used in medical surgical applications beeing similar to extracellular matrix (ECM) and beeing a biocompatible a biodegredable material.Peptide-based scaffolds represent another very import biocompatible material that can support cell growth.
Methods:
HA based composite containing self assembled,small peptides nano-tubes(FmocFF)was selected based on its netlike 3D structure.Cell culture analysis showed that the composite was non-toxix and allowed cell attachment.All animal study was carried according to the approval of the University Commettee for Animal Research. The right eye of laboratory rat was cut within the meninges and sparing the vasculature.HA-FmocFF composite was implanted at the lesion site.The cotrol group was implanted with 2% unmixed HA.Two months following the injury the optic ne were analysed by immunohistochemical preparation. Longitudinal sections were labeled with GAP43 antibody and neurotracer,cholera toxin subunit beta, to determine axonal regeneration.
Results:
The HA-FcmocFF composite was found to be non-toxic and biocompatible to the optic nerve, with no evidence of degeneration.Two months following injury, immunofluorescence analysis presented in most of the ONs a small number of axons that were found adjacent to the injury site.However, about a third of the ONs treated with the HA-FmocFF composite showed a more substantial regeneration towards the optic chiasm.
Conclusions:
HA-FmocFF hydrogel appeared to contribute more to axonal regeneration than hyaluronic acid alone.Partial regeneration can be achieved with specifically designed hydrogels, which offer the regenerating axons a relatively free pathway and net-like 3d scaffold to support and guide their growth beyond the lesion site. Further study is needed, for longer periods of time of follow up, to elucidate the stability of the regenerative process.
Keywords: 607 nanotechnology •
687 regeneration •
629 optic nerve