Molecular dynamics simulations of adsorption and desorption of bone morphogenetic protein-2 on textured hydroxyapatite surfaces.

Interactions between bone morphogenetic protein-2 (BMP-2) and biomaterial surfaces are of great significance in the fields of regenerative medicine and bone tissue engineering. In this work, the adsorption and desorption behaviors of BMP-2 on a series of nano-textured hydroxyapatite (HAP) surfaces were systematically investigated by combined molecular dynamic (MD) simulations and steered molecular dynamic (SMD) simulations. The textured HAP surfaces exhibited nanostructured topographies and played a critical role in the mediation of dynamic behaviors of BMP-2. Compared to the HAP-flat model, the HAP-1:1 group (means ridge vs groove = 1:1) showed the excellent ability to capture BMP-2, less conformation change of BMP-2 molecule, and high cysteine-knot stability during the adsorption and desorption processes. These findings suggest that nano-textured HAP surfaces are more capable of loading BMP-2 molecules, and most importantly, they can help maintain a higher biological activity of BMP-2 cargos. In the present study, for the first time, we have deeply clarified the adsorption and desorption dynamics of BMP-2 on various nano-textured HAP surfaces at the atomic level, which can provide significant guidelines for the future design of BMP-2-based tissue engineering implants/scaffolds. STATEMENT OF SIGNIFICANCE: By using combined molecular dynamic (MD) simulations and steered molecular dynamic (SMD) simulations, the adsorption and desorption dynamics of bone morphogenetic protein-2 (BMP-2) dimer on a series of nano-textured hydroxyapatite (HAP) surfaces at the atomic level were presented in details for the first time. We have proved that the HAP-1:1 model (means ridge vs groove = 1:1) possessed excellent ability to capture BMP-2, less conformation change, and high cysteine-knot stability. As a result, the nano-textured topography of HAP-1:1 could maintain a relatively high biological activity of BMP-2 cargos. This work could provide theoretical guidelines for the design of BMP-2-based implants/scaffolds for bone tissue engineering.