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

Abstract

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.

Strategies to improve the performance of polyetheretherketone (PEEK) as orthopedic implants: from surface modification to addition of bioactive materials

“…Short amino acid sequences derived from the active structural domains of proteins have shown strong potential for application due to their lower cost, ease of synthesis, and protein-like function. 113 An osteoinductive oligopeptide called bone-forming peptide (BFP, in a sequence of GQGFSYPYKAVFSTQ) originated from bone morphogenetic protein-7 (BMP-7) was proved to have excellent osteogenic activity and bone formation activity, even This journal is © The Royal Society of Chemistry 2024…”

“…Short amino acid sequences derived from the active structural domains of proteins have shown strong potential for application due to their lower cost, ease of synthesis, and protein-like function. 113…”

Functionalization of 3D printed polymeric bioresorbable stents with a dual cell-adhesive peptidic platform combining RGDS and YIGSR sequences

“…Furthermore, distinct bioactive peptides can be combined in a single biomimetic molecule to exert synergistic or complementary effects on the surface of an implant. 36–38…”

“…Furthermore, distinct bioactive peptides can be combined in a single biomimetic molecule to exert synergistic or complementary effects on the surface of an implant. [36][37][38] This work presents the functionalization of novel 3Dprinted polymeric BRS fabricated by solvent-cast direct-write (SC-DW) technique with EC adhesive peptides. Stents have been manufactured with poly-L-lactic acid (PLLA) and poly(Llactic-co-ε-caprolactone) (PLCL).…”

Protease-degradable hydrogels with multifunctional biomimetic peptides for bone tissue engineering

“…Consequently, the incorporation of BMP-2-derived peptides together with cell adhesive sequences (mainly RGD) in a well-defined manner is a promising approach to provide hydrogels with osteogenic activity ( Oliver-Cervelló et al, 2021 ). In this regard, we recently developed a multifunctional biomimetic peptide incorporating the RGD and DWIVA (a sequence derived from the wrist epitope of BMP-2) peptides with the capacity to synergistically promote cell adhesion and osteogenic differentiation on model 2D materials in vitro and promote new bone formation on titanium implants in vivo ( Oliver-Cervelló et al, 2021 ; Oliver-Cervelló et al, 2022 ).…”