Three-dimensional nanocomposite scaffolds for bone tissue engineering: from design to application

Abstract

Selective laser sintering (SLS), a rapid prototyping technology, was investigated for producing bone tissue engineering scaffolds. Completely biodegradable osteoconductive calcium phosphate (Ca-P)/poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) scaffolds were successfully fabricated via SLS using Ca-P/PHBV nanocomposite microspheres. In the SLS manufacturing route, the architecture of tissue engineering scaffolds (pore shape, size, interconnectivity, etc.) can be designed and the sintering process can be optimized for obtaining scaffolds with desirable porous structures and mechanical properties. SLS was also shown to be very effective in producing highly complex porous structures using nanocomposite microspheres. To render SLS-formed Ca-P/PHBV scaffolds osteoinductive, recombinant human bone morphogenetic protein-2 (rhBMP-2) could be loaded onto the scaffolds. For achieving a controlled release of rhBMP-2 from scaffolds, surface modification of Ca-P/PHBV scaffolds by gelatin entrapment and heparin immobilization was needed. The immobilized heparin provided binding affinity for rhBMP-2. Surface modified Ca-P/PHBV nanocomposite scaffolds loaded with rhBMP-2 enhanced the proliferation of human umbilical cord derived mesenchymal stem cells (hUCMSCs) and also their alkaline phosphatase activity. In in vivo experiments using a rabbit model, surface modified Ca-P/PHBV nanocomposite scaffolds loaded with rhBMP-2 promoted ectopic bone formation, exhibiting their osteoinductivity. The strategy of combining advanced scaffold fabrication, nanocomposite material, and controlled growth factor delivery is promising for bone tissue regeneration.