Mimicking Bone Extracellular Matrix: From BMP-2-Derived Sequences to Osteogenic-Multifunctional Coatings, Adv. Health. Mater., 2022
Lluís Oliver-Cervelló, Helena Martin-Gómez, Nandin Mandakhbayar, Young-Woo Jo, Elisabetta Ada Cavalcanti-Adam, Hae-Won Kim, Maria-Pau Ginebra, Jung-Hwan Lee, and Carlos Mas-Moruno*
Cell–material interactions are regulated by mimicking bone extracellular
matrix on the surface of biomaterials. In this regard, reproducing the
extracellular conditions that promote integrin and growth factor (GF) signaling
is a major goal to trigger bone regeneration. Thus, the use of synthetic
osteogenic domains derived from bone morphogenetic protein 2 (BMP-2) is
gaining increasing attention, as this strategy is devoid of the clinical risks
associated with this molecule. In this work, the wrist and knuckle epitopes of
BMP-2 are screened to identify peptides with potential osteogenic properties.
The most active sequences (the DWIVA motif and its cyclic version) are
combined with the cell adhesive RGD peptide (linear and cyclic variants), to
produce tailor-made biomimetic peptides presenting the bioactive cues in a
chemically and geometrically defined manner. Such multifunctional peptides
are next used to functionalize titanium surfaces. Biological characterization
with mesenchymal stem cells demonstrates the ability of the biointerfaces to
synergistically enhance cell adhesion and osteogenic differentiation.
Furthermore, in vivo studies in rat calvarial defects prove the capacity of the
biomimetic coatings to improve new bone formation and reduce fibrous tissue
thickness. These results highlight the potential of mimicking integrin-GF
signaling with synthetic peptides, without the need for exogenous GFs.