BMP-2 release and dose-response studies in hydroxyapatite and β-tricalcium phosphate

Abstract

The purpose of this study is to compare in vivo retention of BMP-2 and bone induction in HAp (porosity: 60-80%, pore size: 100-600 µm, sintering temperature: 800 • C, surface area: 1 m 2 /g) and β-TCP (porosity: 75%, pore size: 100-400 µm, sintering temperature: 1050 • C, surface area: 4 m 2 /g). We estimated the in vivo release profile of 125 I-labeled BMP-2 and bone induction of hard tissues histologically. The amount of BMP-2 remaining in the β-TCP at 1 day after implantation was 49.6%, while the amount was 34.0% in the HAp. Furthermore, the HAp and β-TCP containing 0.0, 0.05, 0.1, 0.3, 0.5, 1.0, 5.0 µg of BMP-2 were implanted into the back subcutis of 4-week old Wistar rats. At 3 weeks after implantation, the ceramics were explanted and evaluated histologically. The HAp/BMP-2 (5.0 µg) system showed 3.0% in the total volume of bone at 3 weeks, while only in the β-TCP/BMP-2 (5.0 µg) system showed 32.5%. These results indicate that the absorbable β-TCP block may be an effective bioceramic for bone induction to deliver BMP-2 to the site of action.

Growth factor delivery: How surface interactions modulate release in vitro and in vivo

“…For example, hydroxyapatite scaffolds with a surface area of 1m 2 /g retained 34% of their adsorbed rhBMP-2 after 24 hours, whereas β-tricalcium phosphate scaffolds with a surface area of 4m 2 /g retained 49.6% of their adsorbed rhBMP-2. After this initial burst release their release rates were similar in a mouse subcutaneous site (151). Alternatively, among rat demineralized bone matrix, bovine hydroxyapatite particles, synthetic hydroxyapatite particles, tricalcium phosphate, delipidated bovine bone matrix, coral-derived hydroxyapatite, human demineralized bone matrix, human bone powder, human bone mineral, human irradiated bone chips there was no clear trend relating particle size, which would regulate the available surface area for rhBMP-2 binding, with release kinetics in rat subcutaneous sites (41).…”

Studies of bone morphogenetic protein-based surgical repair

“…HAp/rhBMP-7 composites have also demonstrated success in solid spinal fusion as compared to HAp without rhBMP-7 and autograft in a sheep model [169], as well as success in baboon orthotopic calvarial defects in relatively low dosages [170]. However, as recently revealed by Tazaki et al ., β-TCP may make a more effective rhBMP carrier due to its slower release rate as compared to HAp [171]. …”

Use and efficacy of bone morphogenetic proteins in fracture healing

“…The historical approach of administrating larger amounts of BMPs in an effort to enhance the efficacy might result in the opposite effect. Recent studies using sophisticated biomaterials as BMP carriers show better results with lower doses, corresponding more with physiological concentrations [48]. …”