Enhancement of the Effects of Exfoliated Carbon Nanofibers by Bone Morphogenetic Protein in a Rat Femoral Fracture Model

Abstract

Exfoliated carbon nanofibers (ExCNFs) are expected to serve as excellent scaffolds for promoting and guiding bone-tissue regeneration. We aimed to enhance the effects of ExCNFs with bone morphogenetic proteins (BMPs) and examine their feasibility and safety in clinical applications using a rat femoral fracture model. Group I (n ¼ 16) animals were implanted with control MedGEL. Group II (n ¼ 17) animals were implanted with MedGEL containing ExCNFs. Group III (n ¼ 15) animals were implanted with MedGEL containing 1 mg rhBMP-2. Group IV (n ¼ 15) animals were implanted with MedGEL containing 1 mg rhBMP-2 and ExCNFs. The rats were euthanized after 6 weeks, and their fractured femurs were explanted and assessed by manual palpation, radiographs, and highresolution microcomputerized tomography (micro-CT); the femurs were also subjected to biomechanical and histological analysis. The fusion rates in Group IV (73.3%) were considerably higher than those in Groups I (25. Keywords: exfoliated carbon nanofiber; bone morphogenetic protein; fracture healing; rat femoral fracture model; scaffold Bone morphogenetic proteins (BMPs) are members of the transforming growth factor b superfamily and are powerful osteoinductive molecules. The osteoinductive effects of recombinant human BMPs (rhBMPs) in surgical procedures such as fracture repair, healing of critical-size bone defects, and spinal fusion have been demonstrated in animal models and clinical trials; furthermore, rhBMP-2 and rhBMP-7 have been approved for clinical use. [1][2][3][4][5] Unfortunately, the results of clinical trials show that high doses of BMPs are required to induce adequate bone fusion, as the molecules are soluble and easily diffuse away from the fusion site, becoming inactivated in vivo. 6 In addition, the usefulness of BMPs is limited by their high costs. To address these problems, a number of strategies are being developed to generate safer, less expensive, and more efficacious spinal fusion using rhBMP. However, the efficient immobilization of BMPs onto carriers at low dosage while maintaining desirable in vivo regenerative action remains as a major challenge in bone regeneration research and practice. 7,8 The required rhBMP-2 level in humans, even for the FDA-approved collagen sponge-incorporated treatment, is much higher (over six orders of magnitude greater) than that used for in vitro cell level evaluation and in vivo animal studies. 7,9 Several ongoing investigations aim to develop a scaffold that functions as a delivery vehicle, providing cells with a more controlled and sustained release of bioactive molecules to maintain the local growth factor concentration within the therapeutic range.Carbon nanotubes (CNTs) have received much attention because of their interesting properties, including their exceptional mechanical 10 and high electrical and thermal conductivity, 11 which facilitate their use as reinforcements or additives in materials such as plastics, metals, and ceramics to improve the properties of the materials and introduce nove...

Enhancement of the effects of intermittent parathyroid hormone (1-34) by bone morphogenetic protein in a rat femoral open fracture model

“…Results of manual palpation and radiographic assessment tended to enhance bone healing in group II compared with group I, and group V showed significantly enhanced bone healing during manual palpation, radiographic assessment, and bone volume fraction (BV/TV) during micro-CT analysis. The results were comparable with our previous findings [11, 12] indicating that the application of 1 μg of rhBMP-2 with carrier effectively enhanced bone healing in a rat model of femoral fractures, although it was not enough to achieve complete bone union; 10 μg of rhBMP-2 was necessary for complete bone union. BMP-2 is available for use in the clinical setting, but its expense is problematic.…”

Staphylococcal enterotoxin C2 promotes osteogenesis of mesenchymal stem cells and accelerates fracture healing

“…The fractures were scored as described previously. 15 Fracture union was assessed according to the mineralized callus that bridges the fracture line (right side, one point; left side, one point; anterior side, one point; posterior side, one point). The score was estimated by two independent investigators blinded to the treatments.…”

BMP-2 Promotes Bone Formation in Bone Defects in Which Bone Remodeling Is Suppressed by Long-term and High-dose Zoledronic Acid

“…Fourth, we did not perform biomechanical testing that could quantify the degree of bony union. Instead, we evaluated bony union by the manual palpation method [13,21,22,23].…”

“…Manual palpation is a sensitive and speci c method of assessing bone fusion [13,21,22,23]. Manual palpation with varus/valgus and anterior/posterior angulated force was performed for all harvested specimens with a particular focus at the defect region.…”