Mimicking Bone Extracellular Matrix: From BMP‐2‐Derived Sequences to Osteogenic‐Multifunctional Coatings

• Published in: Advanced healthcare materials Vol. 11; no. 20; pp. e2201339 - n/a
• Main Authors: Oliver‐Cervelló, Lluís, Martin‐Gómez, Helena, Mandakhbayar, Nandin, Jo, Young‐Woo, Cavalcanti‐Adam, Elisabetta Ada, Kim, Hae‐Won, Ginebra, Maria‐Pau, Lee, Jung‐Hwan, Mas‐Moruno, Carlos
• Format: Journal Article
• Language: English
• Published: Germany 01.10.2022
• Subjects: Animals; Biocompatible Materials; biomimetic peptides; Bone Morphogenetic Protein 2 - chemistry; Bone Morphogenetic Protein 2 - pharmacology; Bone Regeneration; cell adhesions; Cell Differentiation; Epitopes; Extracellular Matrix; Integrins; multifunctionality; Osteogenesis; osteogenic differentiation; Peptides - chemistry; Peptides - pharmacology; Rats; RGD‐DWIVA; Titanium; titanium biofunctionalization; RGD-DWIVA; cell adhesions; biomimetic peptides; osteogenic differentiation; titanium biofunctionalization; multifunctionality
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202201339

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. Reproducing bone extracellular matrix is paramount to improve cell‐material interactions. Here, after screening bone morphogenetic protein 2‐derived sequences, biomimetic peptides with adhesive and osteoinductive capacity with a well‐defined geometrical disposition are engineered. Functionalized titanium with the peptides demonstrate to synergistically enhance mesenchymal stem cells adhesion and osteogenic differentiation and to promote new bone formation in vivo.