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.

中文翻译：

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骨形态发生蛋白2在织构羟基磷灰石表面吸附和解吸的分子动力学模拟

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中具有重要意义。在这项工作中，通过组合分子动力学（MD）模拟和转向分子动力学（SMD）模拟，系统地研究了BMP-2在一系列纳米结构化羟基磷灰石（HAP）表面上的吸附和解吸行为。带有纹理的HAP表面表现出纳米结构的形貌，并在BMP-2动力学行为的介导中发挥了关键作用。与HAP-flat模型相比，HAP-1：1组（平均脊对凹槽= 1：1）显示出优异的捕获BMP-2的能力，较少的BMP-2分子构象变化以及较高的半胱氨酸结稳定性在吸附和解吸过程中。这些发现表明，纳米结构的HAP表面更有能力装载BMP-2分子，最重要的是，它们可以帮助维持BMP-2货物更高的生物活性。在本研究中，我们首次深入阐明了BMP-2在原子级的各种纳米织构HAP表面上的吸附和解吸动力学，这可以为将来基于BMP-2的设计提供重要指导。组织工程植入物/支架。

重要声明

通过使用组合分子动力学（MD）模拟和导向分子动力学（SMD）模拟，骨形态发生蛋白2（BMP-2）二聚体在一系列原子级纳米结构化羟基磷灰石（HAP）表面上的吸附和解吸动力学级别是首次详细介绍。我们已经证明，HAP-1：1模型（脊与凹槽的平均比为1：1）具有出色的捕获BMP-2的能力，较少的构象变化和较高的半胱氨酸结稳定性。结果，HAP-1：1的纳米织构形貌可以维持BMP-2货物相对较高的生物活性。这项工作可以为骨组织工程基于BMP-2的植入物/支架的设计提供理论指导。