FRG: Mechanically- and Biologically-Active Nickel-Titanium Foamas Biomimetic Material for Skeletal Repair

生物工程的最大挑战之一是人类骨骼系统的有效修复。 同时，骨是了解材料结构-性能关系的非常丰富的基质。 尽管数十年的研究和对人类健康和生活质量的重要性，骨骼修复的理想系统尚未实现。 合成新型仿生微米和纳米结构材料的能力将使设计用于触发骨修复的材料的开发成为可能，并且可能在人工系统中实现骨的显着特性。 已经开发出允许骨长入用于器械固定的多孔金属涂层，但是成功受到涂层脱粘以及骨生长生物学不可预测性的限制。该项目探索了将全多孔金属泡沫用于植入器械的替代方法，该方法既提供了理想的骨长入多孔结构，又降低了植入物刚度，从而减少了固体金属植入物的应力遮挡问题。这种方法结合了钛或钛合金泡沫的内表面改性，自组装聚合物被设计为具有生物活性，并以这种方式招募适当的细胞在孔隙体积内生长骨。 超分子聚合物也被用于这个项目中，以封装骨细胞在其自组装在金属泡沫的内部。 在项目中使用多孔钛的分析建模，以提供弹性模量的良好估计，并使用有限元分析预测骨填充孔隙时的应力。该重点研究小组项目由材料研究部的聚合物和金属项目以及土木和机械系统部的材料力学和结构项目共同资助。 这个跨学科的项目旨在开发具有与骨骼相当模量的超弹性镍钛金属泡沫，其内表面含有生物活性材料，可促进骨骼快速生长。 鉴于其广泛的可恢复变形，这些超弹性合金可能有助于机械刺激骨细胞，并将实现一种新型插入技术。拟议的工作整合了冶金合成（Dunand），自组装（Stupp）和生物力学（Brinson）三个小组的能力，以开发具有优化骨骼修复新功能的机械和生物活性的拟骨材料。重叠的研究和合作互动将采用成功的框架，在钛泡沫以前的计划开发。在Dunand实验室中创建的多孔NiTi样品将通过Stupp实验室的超分子聚合物涂层的自组装转化为生物活性材料。将通过骨长入研究（Stupp）对这些生物活性材料的生物活性进行研究，并通过循环原位加载（Brinson）将其与机械性能联系起来。生物活性的反馈（Stupp）作为负载的函数，来自建模的孔形态和局部性质（Brinson）将反过来建议泡沫加工的改进（Dunand）。作为一个研究领域，骨骼修复具有广泛的影响，因为它不仅对人类健康，人类生产力和生活质量至关重要，而且同时具有高度的跨学科性，因此对研究生和本科生教育有很大的影响。 该计划中的主题方法为学生的跨学科培训提供了一个很好的机会，将先进的冶金学，有机化学，细胞生物学和力学结合起来，研究一个复杂的问题。 该项目的跨学科性质也是一个很好的平台，可以使用机械适应性，自我修复材料作为模型，在材料的微观结构和纳米结构的仿生设计方面产生新的想法。

One of the great challenges in bioengineering is the effective repair of the human skeletal system. At the same time, bone is a very rich substrate to learn about structure-property relations in materials. Despite decades of research and the importance for human health and quality of life, ideal systems for skeletal repair have not yet been achieved. The ability to synthesize novel biomimetic micro- and nanostructured materials will enable the development of materials designed to trigger bone repair and perhaps to achieve the remarkable properties of bone in artificial systems. Porous metal coatings that allow bone ingrowth for device fixation have been developed, however success is limited by debonding of the coatings, as well as by the biological unpredictability of bone growth. This project explores the alternative approach of using fully porous metallic foam for the implant device, which both provides a porous structure ideal for bony ingrowth and lowers implant stiffness, thereby reducing stress-shielding problems seen with solid metallic implants. This approach combines with the modification of internal surfaces in titanium or titanium alloy foams with self-assembling polymers designed to be bioactive and this way recruit the appropriate cells to grow bone within the pore volume. The supramolecular polymers are also used in this project to encapsulate bone cells during their self-assembly in the interior of metallic foams. Analytical modeling of the porous Ti is used in the project to provide good estimates of the elastic moduli, and using finite element analyses stresses are predicted as bone fills the pores. This Focused Research Group project is being co-funded by the Polymers and Metals Programs in the Division of Materials Research and the Mechanics and Structures of Materials Program in the Division of Civil and Mechanical Systems. This interdisciplinary project aims to develop superelastic nickel-titanium metallic foams with moduli comparable to bone, which contain bioactive materials on their internal surfaces that invite rapid bone growth. These superelastic alloys may be useful for stimulating bone cells mechanically given their extensive recoverable deformation and will enable a novel insertion technique. The proposed work integrates the capabilities of three groups in metallurgical synthesis (Dunand), self-assembly (Stupp), and biomechanics (Brinson) to develop a mechanically- and biologically-active osteomimetic material with novel functions for optimized skeletal repair. Overlapping research and collaborative interactions will be pursued using the successful framework that was developed in a previous program on Ti foams. Porous NiTi samples created in the Dunand laboratory will be transformed into bioactive materials by self-assembly of supramolecular polymer coatings from the Stupp laboratory. These bioactive materials will be investigated for biological activity via bone ingrowth studies (Stupp) and linked to mechanical properties via cyclic in situ loading (Brinson). Feedback on the bioactivity (Stupp) as a function of loading, pore morphology and local properties from modeling (Brinson) will in turn suggest improvements in foam processing (Dunand).As a research area, skeletal repair has broad impact because it is not only critically important to human health, human productivity, and quality of life, but it is at the same time highly interdisciplinary, and can therefore have great impact on graduate and undergraduate education. The approach to the subject in this proposed program offers a great opportunity for interdisciplinary training of students, integrating advanced metallurgy, organic chemistry, cell biology and mechanics to investigate a complex problem. The project's interdisciplinary nature is also a good platform to generate new ideas on biomimetic design of microstructure and nanostructure in materials using a mechanically adaptable, self-healing material as the model.