Abstract
In situ endothelialization, aiming to create implantation surfaces capable of self-endothelialization,
seems to be an extremely promising solution, particularly on those blood-contacting
surfaces. In this research study, we immobilized the soluble semaphorin 4D (SEMA4D)
and C-X-C motif chemokine ligand 12 (CXCL12) biomolecules together with heparin onto
the metal-based biomaterial surfaces to achieve in situ endothelialization of modified
samples both by stimulating the neighboring endothelial cells (ECs) migration and
by capturing the circulating endothelial progenitor cells (EPCs) directly from the
blood circulation. X-ray photoelectron spectroscopy data demonstrate the successful
immobilization of SEMA4D and CXCL12. Due to the presence of heparin, hemocompatibility
was also improved after modification. Although EC migration was mainly mediated by
SEMA4D with the coordination of CXCL12, EC proliferation and haptotaxis property were
also enhanced, while EC chemotaxis was slightly suppressed because the further immobilization
of CXCL12 influences the release of SEMA4D. The results of the ex vivo EPC capturing
assay indicated the mobilization of CXCL12 promotes EPC adhesion. In vivo implantation
further demonstrated that CXCL12 cooperates with SEMA4D to promote a process of in
situ endothelialization.
Keywords
in situ endothelialization - endothelial cell migration - endothelial progenitor cell
- SEMA4D - CXCL12