School of Life Sciences, Guangzhou University, Guangzhou 510006, PR China.
Department of Engineering Mechanics, Dalian University of Technology, Dalian, Liaoning 116023, PR China.
Acta Biomater. 2018 Oct 15;80:121-130. doi: 10.1016/j.actbio.2018.09.019. Epub 2018 Sep 15.
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.
骨形态发生蛋白-2（BMP-2）与生物材料表面之间的相互作用在再生医学和骨组织工程领域具有重要意义。在这项工作中，通过组合分子动力学（MD）模拟和引导分子动力学（SMD）模拟，系统地研究了 BMP-2 在一系列纳米纹理羟基磷灰石（HAP）表面上的吸附和解吸行为。纹理化 HAP 表面表现出纳米结构的形貌，在调节 BMP-2 的动态行为方面起着关键作用。与 HAP-平模型相比，HAP-1:1 组（表示脊与槽的比例为 1:1）表现出出色的捕获 BMP-2 的能力、BMP-2 分子构象变化较小以及在吸附和解吸过程中高半胱氨酸结稳定性。这些发现表明，纳米纹理化 HAP 表面更能够负载 BMP-2 分子，最重要的是，它们可以帮助维持 BMP-2 货物的更高生物学活性。在本研究中，我们首次在原子水平上深入阐明了 BMP-2 在各种纳米纹理化 HAP 表面上的吸附和解吸动力学，这为未来基于 BMP-2 的组织工程植入物/支架的设计提供了重要指导。
通过使用组合分子动力学（MD）模拟和引导分子动力学（SMD）模拟，首次详细呈现了骨形态发生蛋白-2（BMP-2）二聚体在一系列纳米纹理羟基磷灰石（HAP）表面上的原子水平的吸附和解吸动力学。我们已经证明，HAP-1:1 模型（表示脊与槽的比例为 1:1）具有出色的捕获 BMP-2 的能力、较小的构象变化和高半胱氨酸结稳定性。因此，HAP-1:1 的纳米纹理形貌可以保持相对较高的 BMP-2 货物的生物学活性。这项工作可为基于 BMP-2 的骨组织工程植入物/支架的设计提供理论指导。
