Bone defects resulting from trauma, disease, surgery or congenital malformations are a
significant health problem worldwide. Consequently, bone is the second most transplanted tissue
just after blood. Although bone grafts (BGs) have been used for decades to improve bone repairs,
none of the currently available BGs possesses all the desirable characteristics. One way to overcome
such limitations is to introduce the feature of controlled release of active bone-promoting
biomolecules: however, the administration of, e.g., recombinant Bone morphogenetic proteins
(BMPs) have been used in concentrations overshooting physiologically occurring concentrations
and has thus raised concerns as documented side effects were recorded. Secondly, most such
biomolecules are very sensitive to organic solvents and this hinders their use. Here, we present a
novel xeno-hybrid bone graft, SmartBonePep®, with a new type of biomolecule (i.e., intrinsically
disordered proteins, IDPs) that is both resistant to processing with organic solvent and both triggers
bone cells proliferation and differentiation. SmartBonePep® is an advanced and improved
modification of SmartBone®, which is a bone substitute produced by combining naturally-derived
mineral bone structures with resorbable polymers and collagen fragments. Not only have we
demonstrated that Intrinsically Disordered Proteins (IDPs) can be successfully and safely loaded
onto a SmartBonePep®, withstanding the hefty manufacturing processes, but also made them
bioavailable in a tuneable manner and proved that these biomolecules are a robust and resilient
biomolecule family, being a better candidate with respect to other biomolecules for effectively
producing the next generation bone grafts. Most other biomolecules which enhances bone
formation, e.g., BMP, would not have tolerated the organic solvent used to produce SmartBonePep®.