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.

Design and Use of Chimeric Proteins Containing a Collagen-Binding Domain for Wound Healing and Bone Regeneration

“…administration of CBD-BMP4 as treatment for a mouse cranial bone defect  significant improvement in the ossification area of the defect (58% vs 37% for BMP4)  the CBD of fibronectin itself had a small positive effect upon induction of bone formation (195) implantation of functionalized collagen membranes in pig full-thickness wounds  EPLQLKM peptide displays a high specific affinity for bone marrowderived MSC  promotion of a higher healing rate, with numerous infiltrating cells and high blood vessel density, compared to the collagen membrane alone CBD-RGD [ WREPSFMALS ] (196) intramuscular implantation in rats of collagen sponges, functionalized with BMP2 and the peptide CBD-RGD  promotion of the osteogenesis within the implant, displaying more bone trabeculae and mineralized matrix, in comparison with a collagen sponge loaded with either BMP2 or the peptide alone.  BMP2 was employed at a subfunctional dose CBD-OC-FN9-10…”

Photocrosslinkable chitosan hydrogels functionalized with the RGD peptide and phosphoserine to enhance osteogenesis

“…22 As an alternative, numerous studies have focused on the employment of cell adhesion motifs containing RGD to enhance cell-matrix interactions. 26 The incorporation of RGD-containing peptides onto biomaterial surfaces has been shown to enhance cell adhesion and osteogenic differentiation. 32 Moreover, recent studies suggest that phosphoserine is an effective functional group in inducing biomineralization.…”

Osteogenic molecules for clinical applications: improving the BMP-collagen system

“…7). 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 orthopaedics (Visser et al, 2013).…”