Collaborative Research: Biomimetic Bone: From Nano- to Micro-Structure

技术部分：骨是一种层次化的复合材料，在纳米尺度上由分散在自组装的胶原纤维间隙中的羟基磷灰石(HA)纳米晶体组成的相互渗透的网络组成。本研究的目的是结合仿生加工技术，合成具有仿骨层次结构的胶原-羟基磷灰石复合材料，从而再现其力学性能。这项工作通过将骨骼的互穿纳米结构整合到下一个层次：骨骼的片层微结构，扩展了先前在模拟骨骼互穿纳米结构方面的成功。为了实现这一目标，将使用液晶前体胶原蛋白溶液生产密集排列的高度组织的胶原蛋白阵列，然后进行层压，以模仿在骨片中发现的扭曲的胶合板结构。然后，微层状结构将通过PILP过程矿化，这已被证明导致胶原纤维内的矿化，定向的羟基磷灰石纳米晶体嵌入整个胶原纤维的间隙。通过PILP工艺可以获得与骨成分相匹配的60-70wt%的矿物质；然而，即使具有如此高的矿化度，重组胶原海绵的固有孔隙率也阻止了复合材料承受高负荷。因此，就像在骨骼中发现的那样，一种高度组织化的胶原蛋白是重现骨骼特性所必需的。如果密实排列的胶原蛋白阵列可以通过PILP过程矿化，那么应该可以第一次匹配骨骼的弹性、强度和韧性。将对用不同层压策略产生的多层复合材料进行微观机械测试，以评估所生产的结构的质量，以及各种结构参数(如层片厚度、纤维直径/组织、矿化度等)如何。与机械性能相关。最后，由于骨是一种机械结构，将对加载和卸载的胶原阵列进行PILP过程，以确定负载是否在骨形态形成中发挥关键作用。非技术部分：骨是一种非凡的复合材料，其潜在的结构设计可能有助于指导未来复合材料的设计。关于骨的力学性能已经有了很多研究，但由于其层次化的结构，很难分离出每一层结构背后的各种强化和增韧机制的影响。通过开发一种能够模拟不同水平的骨骼结构的体外模型系统，可以在没有这种压倒一切的复杂情况下检查这种特性，并受益于定制复合材料的个别成分的能力。这项工作还具有重要的生物医学意义，无论是在了解骨形成和特性的基础科学水平上，还是在开发下一代整形外科生物材料的应用方面。这种仿生方法有可能导致负重生物可吸收骨替代物的出现，这种替代物在自然骨重建过程中通过细胞过程进行重塑。在教育方面，由于其层级结构，骨为培训学生在材料科学领域的复合材料提供了一个有趣的论坛。教师研究经验(RET)和仿生材料扩展计划(BMOP)等扩展计划将继续进行，其中包括对研究生、本科生和K-12年级学生的培训和扩展。还提出了一个新的推广计划，将向附近城市的水族学家提供公开讲座，向他们展示他们作为爱好喜欢的无脊椎动物生物矿物质(如海胆和软体贝壳)背后的有趣材料科学，以及这些生物矿物质和脊椎动物生物矿物质之间的异同，以展示仿生工程师如何开发新型分层结构的复合材料。

Technical Part: Bone is a hierarchically-structured composite material which at the nanoscale comprises an interpenetrating network of hydroxyapatite (HA) nanocrystals dispersed within the interstices of self-assembled collagen fibrils. The goal of the research is to use a combination of biomimetic processing techniques to synthesize collagen-hydroxyapatite composites with a hierarchical structure emulating bone, and thus reproduce its mechanical properties. The work extends prior success in mimicking the interpenetrating nanostructure of bone, by integrating it to the next level of hierarchy: the lamellar microstructure of bone. To accomplish this goal, densely-packed arrays of highly organized collagen will be produced using liquid-crystalline precursor collagen solutions and then laminated to mimic the twisted plywood structure found in the lamellae of osteonal bone. The microlaminated structures will then be mineralized by the PILP process, which has been shown to lead to intrafibrillar mineralization of collagen, with oriented nanocrystals of hydroxyapatite embedded throughout the interstices of the collagen fibrils. Compositions matching bone, with 60-70 wt% mineral, can be achieved with the PILP process; however, even with this high degree of mineralization, the inherent porosity of reconstituted collagen sponges prevents the composites from supporting high loads. Thus, a highly-organized collagen, as is found in bone, is needed for reproducing the properties of bone. If the densely-packed collagen arrays can be mineralized via the PILP process, it should be possible, for the first time, to match the modulus, strength and toughness of bone. Micromechanical testing will be performed on the multilevel composites generated with different lamination strategies to assess the quality of the structures that are produced, and how the various structural parameters (such as lamellar thickness, fiber diameter/organization, degree of mineralization, etc.) correlate to mechanical properties. Finally, because bone is a mechanical structure, the PILP process will be conducted on both loaded and unloaded collagen arrays to determine if load might play a key role in bone morphogenesis.Non-Technical Part: Bone is a remarkable composite from which its underlying structural design may help guide the design of future composite materials. There have been many studies on the mechanical properties of bone, but because of its hierarchical structure, it is difficult to isolate the effects of various strengthening and toughening mechanisms that underlie each level of structure. By developing an in vitro model system that can mimic separate levels of bone structure, such properties might be examined without this overriding complication, and benefit from the ability to tailor individual components of the composites. This work also has important biomedical implications, both at the fundamental science level with respect to understanding bone formation and properties, and the applications side of developing the next generation of orthopedic biomaterials. This biomimetic approach has the potential to lead to load-bearing bioresorbable bone substitutes which are remodeled through the cellular processes that occur during natural bone remodeling. With respect to education, bone, due to its hierarchical structure, provides an interesting forum for training students about composites in the materials science field. Outreach programs such as Research Experience for Teachers (RET) and Biomimetic-Materials Outreach Program (BMOP) will be continued, which have included training and outreach to students at the graduate, undergraduate, and K-12 levels. A new outreach program is also proposed, in which public lectures will be provided to aquarists in nearby cities to show them the interesting materials science behind the invertebrate biominerals they enjoy as a hobby (such as sea urchins and mollusk shells), and the similarities/differences between these biominerals and vertebrate biominerals, to show how biomimetic engineers are developing novel hierarchically-structured composite materials.