Angiogenesis plays an important role in brain injury repair, which contributes to the reconstruction of regenerative neurovascular niche for promoting axonal regeneration in the lesion area. As a major component of developing brain extracellular matrix, hyaluronic acid (HA) has attracted more attention as a supporting matrix for brain repair. In the present study, HA-KLT hydrogel was developed via modifying HA with a VEGF mimetic peptide of KLT (KLTWQELYQLKYKGI). The characterization of the hydrogel shows that it could provide a porous, three-dimensional scaffold structure, which has a large specific surface area available for cell adhesion and interaction. Compared with the unmodified HA hydrogel, the HA-KLT hydrogel could effectively promote the attachment, spreading and proliferation of endothelial cells in vitro. Furthermore, the pro-angiogenic ability of hydrogels in vivo was evaluated by implanting them into the lesion cavities in the injured rat brain. Our results showed that the hydrogels could form a permissive interface with the host tissues at 4 weeks after implantation. Moreover, they could efficiently inhibit the formation of glial scars at the injured sites. The HA-KLT hydrogel could significantly increase the expression of endoglin/CD105 and promote the formation of blood vessels, suggesting that HA-KLT hydrogel promoted angiogenesis in vivo. Collectively, the HA-KLT hydrogel has the potential to repair brain defects by promoting angiogenesis and inhibiting the formation of glial-derived scar tissue.
Keywords: VEGF mimetic peptide; angiogenesis; hyaluronic acid; traumatic brain injury.
© The Author(s) 2019. Published by Oxford University Press.