Hyaluronic acid hydrogel modified with nogo‐66 receptor antibody and poly‐L‐lysine to promote axon regrowth after spinal cord injury

Abstract

The biomaterials used for central nervous system injury require not only interacting with specific cell adhesion but also specific growth factor receptors to promote nerve regeneration. In this study, hyaluronic acid (HA)-based hydrogels modified with poly-L-lysine (PLL) and nogo-66 receptor antibody (antiNgR) (HA-PLL/antiNgR) were administered to rats after lateral hemisection of the spinal cord. Anti-neurofilament positive axons were found to extend into the HA-PLL/antiNgR hydrogel at 8 weeks after implantation, which shows significant difference compared with HA-PLL or blank control group. Electron micrographs of implanted hydrogels showed that there were more cells and normal axons with myelin in the HA-PLL/antiNgR implant than that of HA-PLL hydrogel. The antiNgR grafted on HA hydrogels could be detected for 8 weeks after transplantation in vivo. All of these properties may facilitate HA-PLL/antiNgR hydrogels to become a promising scaffold for repairing spinal cord injury. Nevertheless, both two kinds of modified hydrogels (HA-PLL/antiNgR and HA-PLL) showed remarkable advantages in supporting angiogenesis, and simultaneously inhibiting the formation of glial scar.

Hyaluronic acid-based scaffold for central neural tissue engineering

“…There are more nerve fibres and b-tubulin-III positive neurons in the HA-anti-NgR hydrogels than in negative controls, as shown in figure 6. In an SCI model, similar results were observed, with few NF-positive fibres discovered in the implants without anti-NgRs, while several NF-positive axons were observed entering the HA-anti-NgR-PLL implants [96]. These in vivo results demonstrated that controlled delivery of antiNgRs supported axonal regeneration, which was of great potential for clinical applications.…”

“…Among them, HA is one of the best candidates for the following reasons: as a major component of soft connective tissue, HA is widely found in most organs and tissues [88,89], especially in the CNS [90]; owing to its high biocompatibility, HA plays a beneficial role in wound healing [91,92]; in recent studies, it has been shown that implantation of HA scaffolds reduces glial scar formation [93,94]. To further enhance axonal regeneration with HA scaffolds, a series of strategies are implemented, and promising results are observed [95,96]. Here, we briefly discuss recent progress on the researches of HA-based scaffolds for CNS regeneration.…”

An in vitro spinal cord injury model to screen neuroregenerative materials

“…fibrin [50]) into bridges increases axon regeneration and disrupts gliotic scar formation in vivo [51][52][53][54]. PDL has additional effects in promoting neuronal cell adhesion [55]. The decision to use both coatings in this study was based on reports in the literature that suggest the attachment and extension of neuronal processes is enhanced on PDL-LAM coated surfaces, compared to PDL alone [56].…”

Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity

“…In addition, its degradation rate and the diffusion of active molecules through it can be modulated by selecting a specific range of molecular weights, or by using different crosslinking agents and fabrication procedures. Furthermore, HA induces a low inflammatory response and may contribute to neovascularization through its lowmolecular weight oligomers [32,38,39]; in addition, it can be functionalized variously to improve cell adhesion, proliferation, migration and differentiation [40,41]. For all these reasons, HA seems a promising material for nerve and brain tissue repair [32,[39][40][41][42].…”