Peptide-Tethered Hydrogel Scaffold Promotes Recovery from Spinal Cord Transection via Synergism with Mesenchymal Stem Cells

Spinal
cord injury (SCI) is one of the most devastating injuries. Treatment
strategies for SCI are required to overcome comprehensive issues.
Implantation of biomaterial scaffolds and stem cells has been demonstrated
to be a promising strategy. However, a comprehensive recovery effect
is difficult to achieve. In the comprehensive treatment process, the
specific roles of the implanted scaffolds and of stem cells in combined
strategy are usually neglected. In this study, a peptide-modified
scaffold is developed based on hyaluronic acid and an adhesive peptide
PPFLML­LKGSTR. Synchrotron radiation micro computed tomography
measurement provides insights to the three-dimensional inner topographical
property and perspective porous structure of the scaffold. The modified
scaffold significantly improves cellular survival and adhesive growth
of mesenchymal stem cells during 3D culture in vitro. After implantation
in transected spinal cord, the modified scaffold and mesenchymal stems
are found to function in synergy to restore injured spinal cord tissue,
with respective strengths. Hindlimb motor function scores exhibit
the most significant impact of the composite implant at 2 weeks post
injury, which is the time secondary injury factors begin to take hold.
Investigation on the secondary injury factors including inflammatory
response and astrocyte overactivity at 10 days post injury reveals
the possible underlying reason. Implants of the scaffold, cells, and
especially the combination of both elicit inhibitory effects on these
adverse factors. The study develops a promising implant for spinal
cord tissue engineering and reveals the roles of the scaffold and
stem cells. More importantly, the results provide the first understanding
of the bioactive peptide PPFLML­LKGSTR concerning its functions
on mesenchymal stem cells and spinal cord tissue restoration.