Recombinant DTβ4-inspired porous 3D vascular graft enhanced antithrombogenicity and recruited circulating CD93 + /CD34 + cells for endothelialization

Abstract

Matching material degradation with host remodeling, including endothelialization and muscular remodeling, is important to vascular regeneration. We fabricated 3D PGS-PCL vascular grafts, which presented tunable polymer components, porosity, mechanical strength, and degrading rate. Furthermore, highly porous structures enabled 3D patterning of conjugated heparin-binding peptide, dimeric thymosin β4 (DTβ4), which played key roles in antiplatelets, fibrinogenesis inhibition, and recruiting circulating progenitor cells, thereafter contributed to high patency rate, and unprecedentedly acquired carotid arterial regeneration in rabbit model. Through single-cell RNA sequencing analysis and cell tracing studies, a subset of endothelial progenitor cells, myeloid-derived CD93 + /CD34 + cells, was identified as the main contributor to final endothelium regeneration. To conclude, DTβ4-inspired porous 3DVGs present adjustable physical properties, superior anticoagulating, and re-endothelializing potentials, which leads to the regeneration of small-caliber artery, thus offering a promising tool for vessel replacement in clinical applications.