Comparative study of poly (lactic-co-glycolic acid)/tricalcium phosphate scaffolds incorporated or coated with osteogenic growth factors for enhancement of bone regeneration

Abstract

Bone graft substitutes are commonly used to treat large bone defects, particularly if they can additionally act as a local delivery system for therapeutic agents capable of enhancing bone regeneration. In this study, composite scaffolds made of poly (lactic-co-glycolic acid) (PLGA) and tricalcium phosphate (TCP) called P/T were fabricated by a low-temperature rapid prototyping technique. In order to optimise the delivery system, two different approaches for loading either the phytomolecule icaritin (ICT) or bone morphogenetic protein-2 (BMP-2) were developed for an in vivo efficacy study. One was an “incorporating approach” in which the growth factor was incorporated into the scaffold during fabrication, whereas the other was a “coating approach” in which the fabricated scaffold was immersed into a preparative solution containing the growth factor. Scaffolds incorporating these growth factors were termed P/T/ICT and P/T/BMP-2, while scaffolds that had these growth factors coated on to them were named, respectively, P/T + ICT and P/T + BMP-2. A P/T scaffold without any loading was used as the control. The bone regeneration effect of these scaffolds was compared in an ulnar bone defect model in rabbits. Bone regeneration and angiogenesis was evaluated by high-resolution peripheral quantitative computed tomography and magnetic resonance imaging postimplantation. Bone regeneration was better with the P/T/ICT scaffolds with an 83.8% improvement compared with the control, and a 72.0% improvement compared with the P/T/BMP-2 treatment. Although the P/T + BMP-2 scaffold demonstrated, as expected, the best overall bone regeneration, the P/T scaffold with incorporated ICT was shown to be an innovative and cost-effective bioactive scaffold which also significantly enhanced bone regeneration with the potential to be validated for orthopaedic applications.