Acceleration of bone formation during fracture healing by poly(pro–hyp–gly)₁₀ and basic fibroblast growth factor containing polycystic kidney disease and collagen‐binding domains from Clostridium histolyticum collagenase

Abstract

Growth factor delivered in combination with animal-derived collagen materials has been used to accelerate bone fracture healing in human patients. However, the introduction of bovine proteins into humans carries the risk of zoonotic and immunologic complications. Here, we developed a collagen-like polypeptide-based bone formation system consisting of poly(Pro-Hyp-Gly)10 , which mimics the triple helical conformation of collagen, and basic fibroblast growth factor (bFGF) fused to the polycystic kidney disease (PKD) domain and collagen-binding domain (CBD) of Clostridium histolyticum collagenase. Circular dichroism spectral analysis showed that when pepsin-soluble bovine type I collagen was treated at 50°C, a positive signal corresponding to the collagen triple helix at 220 nm was not detected. In contrast, poly(Pro-Hyp-Gly)10 retained the 220-nm positive peak, even when treated at 80°C. The combination of the collagen binding-bFGF fusion protein (bFGF-PKD-CBD) with poly(Pro-Hyp-Gly)10 induced greater bone formation compared to bFGF alone in mice bone fracture models. Taken together, these properties suggest that the bFGF-PKD-CBD/poly(Pro-Hyp-Gly)10 composite is a promising material for bone repair in the clinical setting. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1372-1378, 2016.

Augmentation of fracture healing by hydroxyapatite/collagen paste and bone morphogenetic protein‐2 evaluated using a rat femur osteotomy model

“…Growth factors, which stimulate cellular proliferation and/or differentiation, have also been shown to accelerate fracture healing. Mitogenic activity of basic fibroblast growth factor (bFGF) has been proven to be effective when combined with a proper carrier or other system for sustained release . Platelet‐derived growth factors (PDGFs) from blood plasma have been used to augment bone formation and bone defect repair, especially in dentistry .…”

Effect of Single Injection of Recombinant Human Bone Morphogenetic Protein-2-Loaded Artificial Collagen-Like Peptide in a Mouse Segmental Bone Transport Model

“…Collagen materials have been used for the sustained release of rhBMP-2 in clinical settings [9][10][11]. We previously reported that collagen-like polypeptide poly(POG)n is superior to animalderived collagen with regard to thermal stability and lack of pathogenicity and is a useful carrier which retains bFGF well [17,18]. Our preliminary study showed that 2.0 μg of rhBMP-2 without poly(POG)n failed to promote bone formation in a mice bone defect model.…”

“…We previously reported that the artificial collagen-like peptide poly(POG)n was a useful carrier for growth factors. Injection of bFGF-loaded poly(POG)n into fracture sites stimulated periosteal bone formation in mouse fracture models [17,18]. In the present study, we investigated whether a single injection of rhBMP-2-loaded artificial collagen-like peptide gel (rhBMP-2/ACG) accelerates consolidation at the bone defect site and bone union at the docking site in a mouse SBT model.…”

Basic Fibroblast Growth Factor-Anchored Multilayered Mesenchymal Cell Sheets Accelerate Periosteal Bone Formation

“…Images of the entire femur were first obtained, and 10 mm regions of interest (500 slices) were defined at the midfemur. New bone volume and bone mineral content were measured using three-dimensional (3D) image analysis software (Tri-3D-Bon; Ratoc System Engineering Co., Ltd., Tokyo, Japan) as previously described [28, 31]. …”