rhBMP‐2 injected in a calcium phosphate paste (α‐BSM) accelerates healing in the rabbit ulnar osteotomy model

Abstract

This study evaluated the ability of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in an injectable calcium phosphate carrier (a-BSM) to accelerate healing in a rabbit ulna osteotomy model compared to untreated surgical controls. Healing was assessed by radiography, histology and biomechanics. Bilateral mid-ulnar osteotomies were created in 16 skeletally mature rabbits. One limb in each animal was injected with either 0.1 mg rhBMP-Z/a-BSM (BMP) ( N = 8) or bufferla-BSM (BSM) ( N = 8). Contralateral osteotomies served as untreated surgical controls (SXCT). Gamma scintigrdphy showed 75%, 45% and 5% of the initial '251-rhBMP-2 dose was retained at the osteotomy site at 3 h, 1 week and 3 weeks. The biological activity of rhBMP-2 (alkaline phosphatase activity from bioassay) extracted from a-BSM incubated in vitro up to 30 days at 37 "C was unchanged. Radiographs demonstrated complete bridging of the BMP limbs at 4 weeks whereas none of the BSM or SXCT limbs were bridged. Post-mortem peripheral quantitative computed tomography determined mineralized callus area was 62% greater in BMP limbs compared to SXCT limbs. Torsional stiffness and strength were 63% and 103% greater in BMP limbs compared to SXCT limbs. There was no difference in torsional properties between BSM and SXCT limbs. Failure occurred outside the osteotomy in four out of seven of the BMP limbs. All BSM and SXCT limbs failed through the osteotomy. Histology showed bony bridging of the osteotomy and no residual carrier in the BMP limbs. BSM and SXCT groups showed less mature calluses composed of primarily fibrocartilaginous tissue and immature bone in the osteotomy gap. These data indicate rhBMP-2 delivered in a-BSM accelerated healing in a rabbit ulna osteotomy model compared to BSM and SXCT groups.

Calcium Phosphate Cement with BMP-2-loaded Gelatin Microspheres Enhances Bone Healing in Osteoporosis: A Pilot Study

“…Variants of the BMP-2 genes are associated with familial osteoporosis, and rhBMP-2 can reverse bone loss in osteopenic mice [31,32]. Controlled release of rhBMP-2 can be obtained easily when the protein is mixed with CPC during cement setting, and rhBMP-2/CPC is effective in bridging critical-sized bone defects without osteoporosis [4,11,28]. Therefore, rhBMP-2 was chosen to enhance osteoinduction of CPC in our research.…”

“…rhBMP-2 is widely used to enhance osteoinduction of bone substitutes [8,11,17,25,28,29]. In several studies rhBMP-2/carrier formulations were associated with bridging of critical-sized bone defects [11,28,29], but rhBMP-2/CPC was the only combination to restore torsional mechanical properties equivalent to those of normal bone [29].…”

“…In several studies rhBMP-2/carrier formulations were associated with bridging of critical-sized bone defects [11,28,29], but rhBMP-2/CPC was the only combination to restore torsional mechanical properties equivalent to those of normal bone [29]. The weakness of rhBMP-2/CPC is the slow release One or more of the authors (ML, XL) have received funding from a research grant at the Chinese People's Liberation Army (Grant Number of 06MA090) and a grant of Gansu Natural Science Foundation (Grant Number of 0710RJZA068).…”

Soluble expression and purification of synthetic human bone morphogenetic protein-2 in Escherichia coli

“…In recent years, the results of numerous animal experiments have suggested the future therapeutic benefits of BMPs in bone reconstruction (1,2). It is hoped that the cost drops and BMP eventually becomes as affordable as other recombinant products, enabling its use in majority of indicated patient population.…”

“…The osteoinductive capacity of BMP-2 has been demonstrated in preclinical models and evaluated in clinical trials (1,2). The mature BMP-2 represents the C-terminal sequence of a long precursor protein of 396 amino acids and shows an interchain disulfide bridge connecting the two monomers to form an active dimer (3,4).…”