An injectable composite material containing bone morphogenetic protein‐2 shortens the period of distraction osteogenesis in vivo

Abstract

To investigate new methods that can decrease the duration of bone transport (BT) distraction osteogenesis, we injected composite materials containing recombinant human bone morphogenetic protein-2 (BMP-2) and induced the generation of a callus bridge by rapid segmental transport (4 mm/day) in a rabbit bone defect model. The composite materials consisted of BMP-2 (0, 30, or 100 mg), btricalcium phosphate powder (bTCP, 100 mg/animal; particle size, <100 mm), and polyethylene glycol (PEG; 40 mg/animal). A paste of equivalent composition was percutaneously injected at the lengthening and the docking sites after surgery and after BT, respectively. The radiographic, mechanical, and histological examinations 12 weeks post-operative revealed that the generation of bridging callus in the presence and in the absence of BMP-2 was significantly different. The callus mass in the bone defect region was adequately and consistently developed in the presence of 100 mg of BMP (administered for 6 weeks), and the bones were consolidated in 12 weeks. Such an adequate callus formation was not observed in the control animals without BMP-2 treatment. The result of this experimental study suggests the potential application of BMP-2 in accelerating callus formation and in enabling rapid bone transporting, thereby shortening the treatment period for the repair of diaphyseal bone defects by distraction osteogenesis. ß

Effects of the addition of vancomycin on the physical and handling properties of calcium sulfate bone cement

“…In addition to accelerating fracture healing, bone graft substitutes may also serve as a drug delivery vehicle for various antibiotics, growth factors, and anti-osteoporosis drugs [4][5][6][7][8]. Calcium sulfate is also proposed as a carrier to deliver fibroblast growth factor and simvastatin [19,20].…”

“…Besides the use of different kinds of implants to hold the reduction of displaced fracture fragments during surgeries, intra-operative applications of bone grafts into bone voids are considered to support mechanical stability, or to provide structural replacement to accelerate fracture healing and promote early rehabilitation [3]. In addition to supporting mechanical stability to improve bone defect repair, bone graft substitutes also serve as a controlled drug delivery system for various purposes [4][5][6][7]. A number of studies have reported using bone substitutes to deliver antibiotics locally for open fractures, infection prevention, and osteomyelitis [8].…”

Tissue induction, the relationship between biomaterial’s microenvironment and mesenchymal stem cell differentiation

“…Generally, the protein adsorption (e.g. growth factor) is rarely in the normal condition, but is significant in the growth of new tissue [18].…”

Transport Distraction Osteogenesis With Recombinant Human Bone Morphogenic Protein-2 for Large Calvarial Defect Reconstruction

“…Among the various factors which can induce bone growth, bone morphogenic protein (BMP) is believed to be the primary facilitator of bone regeneration in DO. [13][14][15][16][17][18] BMP belongs to the transforming growth factor β superfamily. It promotes vascular invasion, bone formation, bone remodeling, and bone marrow differentiation by directing cell differentiation of mesenchymal stem cells to become osteoblasts and osteocytes, which in turn build and renew the extracellular matrix.…”

“…rhBMP-2 is known to enhance consolidation, shorten the period of distraction, and eventually accelerate bone regeneration. 13,16,17,22,23 We used a specially designed drug-delivering distraction device for periodic injection of rhBMP-2 during TDO.…”