Biomimetic calcium phosphate bone substitute for bone tissue engineering

Abstract

Event Abstract Back to Event Biomimetic calcium phosphate bone substitute for bone tissue engineering Yuelian Liu1, Tie Liu1, Daniel Wismeijer1 and Klaas De Groot1 1 VU University, Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam, Netherlands Introduction: The treatment of bone defects requires adequate volume of bone tissue, which is of paramount importance to achieve an excellent aesthetic and functional restoration. Synthetic calcium phosphate (CaP) biomaterials are widely used in the regeneration of bone defects because of their chemical similarity to native bone tissue. Currently, there is an increased interest in biomimetic calcium-phosphate materials because of their capacity to delivery bioactive agents (BMP-2) without compromising their bioactivity[1],[2]. As a synthetic alternative to autologous bone grafting, a biomimetic calcium phosphate bone substitute (BioCaP) was developed with two protein delivery modes: 1) protein in the interior of BioCaP (internally-incorporated mode), 2) protein in the coating on the surface of BioCaP (coating-incorporated mode). The aim of this study is to evaluate the osteoinductivity of BioCaP with each delivery mode of BMP-2, and to investigate the therapeutic effectiveness of BioCaP in the repair of a large cylindrical bone defect (8mm in diameter and 13mm in depth) in sheep. Materials and Methods: In an ectopic rat model: To evaluate the osteoinductivity of materials, granules of BioCaP with different carrying modes of BMP-2 were implanted subcutaneously in rats. Samples were collected after five weeks for histomorphometric analysis. Two experimental and three control groups were analyzed (n=6 rats per group). The groups were: (1) BioCaP granules with internally-incorporated BMP-2); (2) BioCaP granules with coating-incorporated BMP-2; (3) BioCaP granules with adsorbed BMP-2; (4) BioCaP granules without a CaP coating or BMP-2; and (5) BioCaP granules with a CaP coating but no BMP-2. In an orthotopic sheep model: To investigate the therapeutic effectiveness of BioCaP with each delivery mode of BMP-2 in the repair of a large cylindrical bone defect (8mm in diameter and 13mm in depth) in sheep, six groups were established: (1) BioCaP only; (2) BioCaP with coating-incorporated BMP-2; (3) BioCaP with internally-incorporated BMP-2; (4) no graft material (negative control); (5) autologous bone (positive control); (6) deproteinized bovine bone (DBB, a commercial product as control). 4 and 8 weeks after implantation, samples were withdrawn for histological and histomorphometric analysis. Results: In vivo data showed that the volume densities of bone, bone marrow, and blood vessels were significantly higher in samples where BMP-2 was incorporated internally or in the coating compared with granules with adsorbed growth factor. BioCaP with BMP-2 showed equal efficacy as autologous bone in the bone defect repair at 8 weeks post-implantation. Both delivery modes of BMP-2 accelerated the bone formation in an early period of 4 weeks. The internally-incorporated mode enhanced bone formation after 8 weeks, showing more efficient than DBB. Within 8 weeks, about half of BioCaP with either internally-incorporated BMP-2 or without BMP-2 was degraded, which was significantly higher than that of BioCaP with coating-incorporated BMP-2. Conclusions: In conclusion, biomimetic calcium phosphate bone substitutes enhance bone formation. Benefiting from these results, BioCaP can be a promising alternative to the autografts for bone tissue engineering. The autologous bone will not be needed clinically in the near future.