A Novel BMP2‐Coprecipitated, Layer‐by‐Layer Assembled Biomimetic Calcium Phosphate Particle: A Biodegradable and Highly Efficient Osteoinducer

Abstract

To repair large-size bone defects, most bone-defect-filling materials in clinic need to obtain osteoinductivity either by mixing them with particulate autologous bone or adsorbing bone morphogenetic protein 2 (BMP2). However, both approaches encounter various limitations. In this study, we hypothesized that our novel particles of biomimetic BMP2-coprecipitated calcium phosphate (BMP2-cop.BioCaP) could serve as an independent and biodegradable osteoinducer to induce bone formation efficiently for these bone-defect-filling materials, for example, deproteinized bovine bone (DBB). We alternately layer-by-layer assembled amorphous and crystalline CaP triply to enable a "bamboo-like" growth of the particles. We functionalized BioCaP by coprecipitating BMP2 into the most outer layer of BioCaP. We monitored the degradation, osteoinductivity, and foreign-body reaction of either BMP2-cop.BioCaP or its combination with DBB in an ectopic site in rats. After 5 weeks, the BMP2-cop.BioCaP significantly induced new bone formation not only alone but also when mixed with DBB. Its osteoinductive efficiency was 10-fold higher than the adsorbed BMP2. Furthermore, BMP2-cop.BioCaP also reduced significantly the host foreign-body reaction to DBB in comparison with the adsorbed BMP2. After a 5-week implantation, more than 90% of BMP2-cop.BioCaP degraded. These findings indicate a promising clinical potential for BMP2-cop.BioCaP in the repair of large-size bone defects.