Functionalization of bone implants with nanodiamond particles and angiopoietin-1 to improve vascularization and bone regeneration

Abstract

One of the major challenges in bone tissue engineering is adequate vascularization within bone substituents for nutrients and oxygen supply. In this study, the production and results of a new, highly functional bone construct consisting of a commercial three-dimensional β-tricalcium phosphate scaffold (β-TCP, ChronOS®) and hydrophilic, functionalized nanodiamond (ND) particles are reported. A 30-fold increase in the active surface area of the ChronOS + ND scaffold was achieved after modification with ND. In addition, immobilization of angiopoietin-1 (Ang-1) via physisorption within the β-TCP + ND scaffold retained the bioactivity of the growth factor. Homogeneous distribution of the ND and Ang-1 within the core of the three-dimensional scaffold was confirmed using ND covalently labelled with Oregon Green. The biological responses of the β-TCP + ND scaffold with and without Ang-1 were studied in a sheep calvaria critical size defect model showing that the β-TCP + ND scaffold improved the blood vessel ingrowth and the β-TCP + ND + ND + Ang-1 scaffold further promoted vascularization and new bone formation. The results demonstrate that the modification of scaffolds with tailored diamond nanoparticles is a valuable method for improving the characteristics of bone implants and enables new approaches in bone tissue engineering.