title: A collagen-targeted biomimetic RGD peptide to promote osteogenesis.
abstract: Osteogenesis is a complex, multifactorial process in which many different signals interact. The bone morphogenetic proteins (BMPs) are the most potent inducers of osteoblastic differentiation, although very high doses of BMPs in combination with collagen type I formulations have to be used for clinical applications. Although integrin-binding arginine-glycine-aspartic acid (RGD) biomimetic peptides have shown some promising abilities to promote the attachment of cells to biomaterials and to direct their differentiation, the linking of these peptides to collagen sponges usually implies chemical manipulation steps. In this study, we describe the design and characterization of a synthetic collagen-targeted RGD biomimetic (CBD-RGD) peptide formed from a collagen-binding domain derived from the von Willebrand factor and the integrin-binding RGD sequence. This peptide was demonstrated to bind to absorbable collagen type I sponges (ACSs) without performing any chemical linking, and to induce the differentiation of MC3T3-E1 mouse preosteoblasts and rat bone marrow-derived mesenchymal stem cells. Furthermore, in vivo experiments showed that ACSs functionalized with CBD-RGD and loaded with a subfunctional dose of BMP-2-formed ectopic bone in rats, while nonfunctionalized sponges loaded with the same amount of BMP-2 did not. These results indicate that the combination of this biomimetic peptide with the currently used collagen+BMP system might be a promising approach to improve osteogenesis and to reduce the doses of BMPs needed in clinical orthopedics.
authors.affiliation: 1 Department of Cell Biology, Genetics and Physiology, Faculty of Science, University of Malaga , Malaga, Spain .
authors.forename: Rick
authors.initials: R
authors.lastname: Visser
authors.forename: Pilar M
authors.initials: PM
authors.lastname: Arrabal
authors.forename: Leonor
authors.initials: L
authors.lastname: Santos-Ruiz
authors.forename: Raul
authors.initials: R
authors.lastname: Fernandez-Barranco
authors.forename: Jose
authors.initials: J
authors.lastname: Becerra
authors.forename: Manuel
authors.initials: M
authors.lastname: Cifuentes
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology*; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002113:Calcification, Physiologic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D016596:Vinculin / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D009842:Oligopeptides; D016596:Vinculin; C047981:arginyl-glycyl-aspartic acid; D000469:Alkaline Phosphatase; D020169:Caspases; D002118:Calcium