Collagen-binding bone morphogenetic protein-2 designed for use in bone tissue engineering

Abstract

Bone tissue engineering using biodegradable porous scaffolds is a promising approach for restoring oral and maxillofacial bone defects. Recently, attempts have been made to incorporate proteins such as growth factors to create bioactive scaffolds that can engage cells to promote tissue formation. Collagen-based scaffolds containing bone morphogenetic protein-2 (BMP2) have been studied for bone formation. However, controlling the initial burst of BMP2 remains difficult. Here we designed a functional chimeric protein composed of BMP2 and a collagen-binding domain (CBD), specifically the A3 domain of von Willebrand factor, to sustain BMP2 release from collagen-based scaffolds. Based on the results of computer-based structural prediction, we prepared a chimeric protein consisting of CBD and BMP2 in this order with a peptide tag for affinity purification. The chimeric protein had a collagen-binding capacity and enhanced osteogenic differentiation of human mesenchymal stem cells. These results are consistent with insights from in silico structural prediction.