RhBMP-2-Conjugated Three-Dimensional-Printed Poly(L-lactide) Scaffold is an Effective Bone Substitute.

Abstract

Bone growth factors, particularly bone morphogenic protein-2 (BMP-2), are required for effective treatment of significant bone loss. Despite the extensive development of bone substitutes, much remains to be desired for wider application in clinical settings. The currently available bone substitutes cannot sustain prolonged BMP-2 release and are inconvenient to use. In this study, we developed a ready-to-use bone substitute by sequential conjugation of BMP to a three-dimensional (3D) poly(L-lactide) (PLLA) scaffoldusing novel molecular adhesive materials that reduced the operation time and sustained prolonged BMP release. A 3D PLLA scaffold was printed and BMP-2 was conjugated with alginate-catechol and collagen. PLLA scaffolds were conjugated with different concentrations of BMP-2 and evaluated for bone regeneration in vitro and in vivo using a mouse calvarial model. The BMP-2 release kinetics were analyzed using ELISA. Histological analysis and micro-CT image analysis were performed to evaluate new bone formation. The 3D structure of the PLLA scaffold had a pore size of 400µm and grid thickness of 187-230µm. BMP-2 was released in an initial burst, followed by a sustained release for 14days. Released BMP-2 maintained osteoinductivity in vitro and in vivo. Micro-computed tomography and histological findings demonstrate that the PLLA scaffold conjugated with 2µg/ml of BMP-2 induced optimal bone regeneration. The 3D-printed PLLA scaffold conjugated with BMP-2 enhanced bone regeneration, demonstrating its potential as a novel bone substitute.