Size-Mediated Adsorption Dynamics, Conformation and Bioactivity of Bone Morphogenetic Protein-2 Onto Silica Nanoparticles.

Delivery of bone morphogenetic protein-2 (BMP-2) carries great promise for the field of bone regenerative medicine. But, how the size and curvature of matrix affect the way BMP-2 binding to the support and in turn influence its bioactivity remain poorly understood. In this contribution, silica nanoparticles (SNPs) with 20 nm, 60 nm and 100 nm (named as SNP20, SNP60, SNP100, respectively) were introduced as models. Based on the models, the nanoscale curvature-mediated adsorption dynamics, conformation, and bioactivity of recombinant human BMP-2 (rhBMP-2) were investigated. Our data showed that SNPs bound rapidly to and induced unfolding of rhBMP-2 molecules, which undermined their interactions with the corresponding receptors on the cell surface and decreased the bioactivities of adsorbed rhBMP-2. In contrast, rhBMP-2 showed increasingly stronger affinity to and lost less secondary structure on the larger SNPs, while better bioactivity was observed on the medium SNP60 surfaces. The results indicated that the size of the SNPs, perhaps because of the contribution of surface curvature, influences the structure and function of the adsorbed BMP-2. This study demonstrates the possibility to mediate the binding, conformation and bioactivity of BMP-2 by tailoring the nanoscale curvature, allowing fabrication of BMP-2-based bone tissue scaffolds with high osteoinductivity at low BMP-2 dosage.