Novel functional materials based on self-assembled protein nanofibers (PNNF): Degradation dynamics of PNNFs/hybrid PNNFs and creation of PNNF/hybrid PNNF micro-scaffolds (step 2)

基于自组装蛋白质纳米纤维 (PNNF) 的新型功能材料：PNNF/混合 PNNF 的降解动力学以及 PNNF/混合 PNNF 微支架的创建（步骤 2）

• 批准号: 252901784
• 负责人: Professor Dr. Klaus D. Jandt
• 金额: --
• 依托单位: Lehrstuhl für Materialwissenschaften
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/252901784?language=en
• 关键词: Novel; functional; materials; based; self

Due to their outstanding biocompatibility and mechanical strength, protein nanofibers (PNNFs) have a high potential for applications in materials science and biomedical engineering. In this stepwise project (3 project steps with 2 years duration each), we aim towards understanding PNNF formation mechanisms and to apply this knowledge by creating novel PNNF based micro-scaffolds (MS) as building blocks for larger structures in tissue regeneration or drug delivery.In the successfully completed first project step, we i) created novel hybrid PNNFs (hPNNFs) consisting of two different plasma proteins, ii) developed a model for PNNF self-assembly that explains the observed experimental results and allows predictions for new PNNFs, iii) created single PNNFs that are stable in solution for at least 4 weeks, and iv) achieved the desired PNNF mechanical stiffness, leading to publications in high impact factor journals. The results of the first project step lay a promising foundation for the second project step.This second step focuses on the advancement of knowledge of PNNF and MS degradation. It contributes to the future goal of designing the biomaterials’ stability to required regeneration kinetics of tissues. We will test two hypotheses: first, that MSs can be fabricated from PNNFs and novel hybrid PNNFs by layer-by-layer (LBL) with micro-contact printing (μCP) approaches, and second, that based on the understanding of the PNNF degradation, MSs with desired target degradation can be created.Our research aims of project step 2 are, therefore, to i) understand the currently unknown degradation mechanisms of the MSs building blocks (PNNFs/hPNNFs), ii) to apply new strategies to fabricate novel MSs based on the self-assembled PNNFs/hPNNFs.To this end, we will initially investigate the PNNF’s and hPNNF’s degradation dynamics using wet state AFM and QCM considering bone regeneration conditions. The results from these experiments will enable us to understand the PNNF degradation mechanism and the impact of the second protein in hPNNFs and of the PNNF/hPNNF dimensions, which are important for tailoring the degradation of the PNNF/hPNNF based MSs. Next, we will create PNNF/hPNNF based single and bilayers, as important intermediate step to fabricate 3D MSs, using LBL dip coating.Finally, we will create 3D-MSs by combining LBL and μCP approaches with the aim to understand and adjust the MS’ degradation properties through the choice of PNNF/hPNNF dimensions as well as the choice of the MS structure.In the third project step (last 2 years), we will tailor the degradation, mechanical properties and, thus, the cellular response to the MSs.We expect that the projected results will significantly advance the knowledge and understanding of PNNFs and have a considerable impact on the application of MSs as biomaterials for tissue regeneration through the flexibility of the PNNF’s and MS’ properties.

由于其出色的生物相容性和机械强度，蛋白质纳米纤维（PNNF）在材料科学和生物医学工程中具有很高的应用潜力。在这个分步项目中（3个项目步骤，每个步骤持续2年），我们的目标是了解PNNF形成机制，并通过创建基于PNNF的新型微支架（MS）作为组织再生或药物输送中更大结构的构建块来应用这些知识。在成功完成的第一个项目步骤中，我们i）创建了由两种不同血浆蛋白组成的新型混合PNNF（hPNNF），ii）开发了一种 PNNF 自组装模型解释了观察到的实验结果并允许预测新的 PNNF，iii) 创建了在溶液中稳定至少 4 周的单个 PNNF，以及 iv) 实现了所需的 PNNF 机械刚度，从而在高影响因子期刊上发表了论文。第一个项目步骤的结果为第二个项目步骤奠定了良好的基础。第二个步骤的重点是 PNNF 和 MS 降解知识的进步。它有助于设计生物材料对组织再生动力学所需的稳定性的未来目标。我们将测试两个假设：首先，MS 可以通过微接触印刷 (μCP) 方法通过逐层 (LBL) 方法由 PNNF 和新型混合 PNNF 制造，其次，基于对 PNNF 降解的理解，可以创建具有所需目标降解的 MS。因此，我们项目步骤 2 的研究目标是 i) 了解当前未知的 MSs构件（PNNFs/hPNNFs）的降解机制，ii）应用新策略来制造基于自组装PNNFs/hPNNFs的新型MSs。为此，我们将首先考虑骨再生条件，使用湿态AFM和QCM研究PNNFs和hPNNFs的降解动力学。这些实验的结果将使我们能够了解 PNNF 降解机制以及 hPNNF 中第二种蛋白质和 PNNF/hPNNF 维度的影响，这对于定制基于 PNNF/hPNNF 的 MS 的降解非常重要。接下来，我们将使用 LBL 浸涂创建基于 PNNF/hPNNF 的单层和双层，作为制造 3D MS 的重要中间步骤。最后，我们将结合 LBL 和 μCP 方法创建 3D-MS，目的是通过选择 PNNF/hPNNF 尺寸以及 MS 结构来了解和调整 MS 的降解特性。在第三个项目步骤中 （过去 2 年），我们将调整降解、机械性能以及细胞对 MS 的反应。我们预计，预计的结果将显着增进对 PNNF 的认识和理解，并通过 PNNF 和 MS 特性的灵活性，对 MS 作为组织再生生物材料的应用产生相当大的影响。