Xenohybrid Bone Graft Containing Intrinsically Disordered Proteins Shows Enhanced In Vitro Bone Formation

Bone defects are a significant health problem worldwide, as bone is the second-most transplanted tissue after blood. Although a myriad of bone grafts (BGs) have been used to treat bone repairs, none of them possesses all the desirable characteristics. An approach to improve BGs is to add bio-active components, however often difficult as BG production may disrupt the biological activities of such molecules. Here, we present a composite xenohybrid BG, SmartBonePep, with a type of biomolecule inspired by intrinsically disordered proteins (IDPs). These synthetic peptides (named P2 and P6) are physically entrapped into the polymer matrix of the composite BG. The effects of SmartBonePep on human osteoblasts were tested. Results showed that SmartBonePep enhanced proliferation and osteogenic effects. In order to verify the bioactivity of P2 and P6, these peptides were tested indirectly by being added to cell culture media too. Here, P2 or P6 exhibited promoting effects on osteogenic-related gene expressions. In this study, we showed highly effective osteoinductive synthetic peptides P2 or P6, which possess proline-rich and intrinsically disordered structural characters. This use of IDPs may provide promising bone enhancement biomolecules for clinical usage.