Comparing ectopic bone growth induced by rhBMP‐2 on an absorbable collagen sponge in rat and rabbit models

Abstract

Recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) is currently employed as an autograft replacement for spinal fusion. The morphogen is incorporated onto its carrier, an absorbable collagen sponge (ACS), in the operating room. Although the effectiveness of the rhBMP-2/ ACS implant in stimulating bone formation in human subjects has now been well established, further investigations of its use are necessary to deepen our understanding of its performance. The objective of the present study was to determine whether fluid released from the rhBMP-2/ACS implant could induce bone growth in tissue sites away from the implant site. We first measured the amount of protein in the fluid released from the rhBMP-2-soaked ACS during intraoperative handling. Variables included soak time and degree of compression. In the compression group that most closely approximated intraoperative conditions, more than 95% of the rhBMP-2 protein was retained by the ACS following a 15-min. soak time. This in vitro study was followed by an in vivo ectopic implant experiment using rat and rabbit models. The animal investigation compared the amount of bone induced by rhBMP-2 solution alone versus the de novo bone formation induced by rhBMP-2/ACS implants with varying concentrations of rhBMP-2. No ossicles were found at the sites where rhBMP-2 solution was injected in either animal species. Twenty-two of the 24 subcutaneous sites in the rats implanted with the rhBMP-2/ACS constructs displayed the presence of the typical 4-and 12-week ossicle. There were no noticeable differences in the size and shape of the ossicles after 4 and 12 weeks. There was a greater percentage of implant sites without ossicles in the rabbits, compared to the rats. ß

Bisphosphonates: therapeutics potential and recent advances in drug delivery

“…Drugs with high molecular weight cannot easily permeate through skin. Sometimes adhesives may not adhere well to all types of skin and maybe uncomfortable to apply (Nishiyama et al, 1996;Hsu et al, 2006).…”

Non-viral gene therapy for bone tissue engineering

“…The studies however have been performed in nude mice, from which it is known that cells are needed to stimulate bone formation. Other animal models such as rat, goat and rabbit are also inducible with an osteogenic material or growth factor 266 . For clinical translation, a cell-free construct would be ideal because harvesting, isolation and culturing of MSCs are time-consuming and costly.…”

The Effect of Recombinant Human Bone Morphogenetic Protein-2 on the Osseointegration of Temporary Anchorage Devices

“…However, for the first time in 1988, these naturally occurring proteins were isolated and genetically reproduced to form recombinant human bone morphogenetic protein, or rhBMP. Like the naturally occurring protein, the recombinant form, according to several preclinical studies, has demonstrated the ability to induce new bone growth [16,18,19,20]. Specifically, rhBMP-2 has been studied more than any other BMP and has been approved by the Food and Drug Administration (FDA) for use in tibial, oral, and spinal surgical procedures.…”

“…Furthermore, studies have shown that when rhBMP-2 is used with a carrier, for example a collagen sponge, it has the ability to improve spinal fusion, increase periodontal new bone formation, and encourage fracture repair. In addition, rhBMP-2 has been used to regenerate defects of the mandible and skull, and help in the treatment of non-union, delayed union, and other skeletal conditions [13,15,18,19].…”