Functionalized Polycaprolactone/Hydroxyapatite Composite Microspheres for Promoting Bone Consolidation in a Rat Distraction Osteogenesis Model

Distraction osteogenesis (DO) is an ideal model to study bone regeneration. The major limitation is the relatively long period required for new bone consolidation. Here, we investigated whether the application of polycaprolactone (PCL) and hydroxyapatite (HA) composite microspheres could enhance bone formation in DO. Pure PCL microspheres and composite PCL and 10% HA microspheres were synthesized. Bone mesenchymal stem cells isolated from green fluorescent protein rats (GFP-rBMSCs) were cultured with microspheres in a rotary bioreactor system. Scanning electron microscopy was used to examine the microstructures. Osteogenic differentiation of rBMSCs was confirmed. Moreover, PCL/HA (20 mg) and PCL (20 mg) were locally administered into the distraction gap in the rat DO model toward the end of the distraction period. Imaging detection, mechanical and histological examinations were performed to assess the quality of the 4-week regenerates. Results showed that the microspheres were of uniform size and monodisperse. After incubation with rBMSCs in culture, PCL/HA microspheres showed a better ability for cell adhesion and osteogenic differentiation compared with PCL microspheres. In vivo, bone volume/total tissue volume, bone mineral density, and mechanical properties of the new callus were significantly higher in the PCL/HA group compared with the PCL group. Histological analyses confirmed improved bone formation and vascularization in PCL/HA group. We presented an effective protocol for the generation of functionalized microspheres and demonstrated implantation of PCL/HA microspheres into the distraction regenerate could significantly enhance bone consolidation. Thus, the application of PCL/HA composite microspheres may be a novel approach for promoting bone regeneration. This article is protected by copyright. All rights reserved © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:961-971, 2020.