In vivo Evaluation of Bone Regeneration by TAT-BMP-2 and Hydrogel Composite

Abstract

Although the need for bone regeneration is gradually increasing due to aging, alveolar bone loss, and osteoporosis, clinical modality is not yet definite. Exogenous bone morphogenetic protein (BMP) should have sufficient bioactivity and be in harmony with carriers by controlled release of biological factors with mechanical support. Recombinant human BMP-2 (rhBMP-2) are currently used in clinics, but their efficacy remains obscure.Contrary to rhBMP-2, inactive polypeptide TAT-BMP-2 fusion protein can be successfully transduced into cells in concentration- and time-dependent manners independent to BMP receptors. Hydrogel, which is made of hyaluronic acid, one of the major components of human connective tissue, shows biocompatibility and releases containing materials in a controlled manner with degradation. This study aims to evaluate bone regeneration radiologically and histologically with the femurs of beagles by combining TAT-BMP-2 with fibrin, hydrogel, and PEEK. The results are as follows:1. TAT-BMP-2 fibrin composite induced superior bone regeneration than the fibrin-only applied subject under isolated condition by PEEK, but statistically not significant.2. The application of hydrogel alone induced partial bone regeneration.3. TAT-BMP-2 hydrogel composite caused superior bone regeneration than the application of hydrogel alone in area, volume analysis (p<0.05).4. TAT-BMP-2 hydrogel composite only induced regeneration of continuity of the outer cortex and showed a more matured, dense structure than the application of hydrogel alone.5. TAT-BMP-2 hydrogel composite decreased dosage for in vivo bone regeneration by 1/1000 of the conventional dosage of rhBMP-2.These results indicate that TAT-BMP-2 hydrogel composite induced effective in vivo bone regeneration by highly efficient protein synthesis through inactive polypeptide TAT-BMP-2 as well as controlled protein releasing through hydrogel.