AbstractIn order to improve collagen bioactivity for regenerative medicine approaches, thymosin‐β4 (Tβ4P) and Human Vitronectin (HVP) derived peptides are grafted to collagen by thiol‐ene Michael addition. Tβ4P and HVP are known to exert a pro‐angiogenic and a pro‐adhesive activity respectively and HVP is involved in osteogenesis promotion. The ability of these peptides to increase collagen cell adhesion and angiogenesis properties is assessed on human cell lines. In particular, HVP‐grafted collagen increased human osteoblast adhesion and cell proliferation: after 24 h, both adhesion and proliferation roughly showed a 4‐fold increase, if compared to pristine collagen. Tβ4P‐grafted collagen promotes Vascular Endothelial Growth Factor (VEGF) gene expression in human vascular cell lines by more than 7 times. These results suggest that HVP‐grafted collagen may be an interesting biomaterial for bone tissue regeneration, while Tβ4P‐grafted collagen is useful for angiogenesis promotion.