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

技术部分：骨是一种分级结构的复合材料，其在纳米级包含分散在自组装胶原纤维间隙内的羟基磷灰石（HA）纳米晶体的互穿网络。 本研究的目的是利用仿生加工技术的组合来合成具有模拟骨的分级结构的胶原-羟基磷灰石复合材料，从而再现其力学性能。 这项工作通过将其整合到下一层次：骨的层状微观结构，扩展了先前在模拟骨的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产生高度组织化的胶原蛋白的密集排列，然后层压以模仿骨细胞层中发现的扭曲胶合板结构。 然后，通过PILP过程将微层结构矿化，PILP过程已显示导致胶原的纤维内矿化，其中羟基磷灰石的定向纳米晶体嵌入整个胶原纤维的间隙中。 用PILP工艺可以实现具有60-70重量%矿物质的与骨匹配的组合物;然而，即使具有这种高矿化度，重构胶原海绵的固有孔隙率也阻止了复合材料支撑高负荷。 因此，需要高度组织化的胶原蛋白（如在骨中发现的）来再现骨的性质。 如果密集堆积的胶原阵列可以通过PILP过程矿化，那么第一次应该可以匹配骨的模量，强度和韧性。 将对采用不同层压策略生成的多级复合材料进行微机械测试，以评估所生产的结构的质量，以及各种结构参数（如层状厚度、纤维直径/组织、矿化度等）与机械性能相关。 最后，由于骨是一种机械结构，PILP过程将在加载和未加载的胶原阵列上进行，以确定载荷是否可能在骨形态发生中起关键作用。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有许多研究，但由于其层次结构，很难将每一层次结构下的各种强化和增韧机制的影响隔离开来。 通过开发一种可以模拟不同层次骨结构的体外模型系统，可以在没有这种压倒一切的并发症的情况下检查这些特性，并从定制复合材料的单个组件的能力中受益。 这项工作也具有重要的生物医学意义，无论是在基础科学水平上了解骨形成和性能，还是在开发下一代骨科生物材料的应用方面。 这种仿生方法有可能导致承重生物可吸收骨替代物，其通过在自然骨重建期间发生的细胞过程进行重建。 在教育方面，由于其层次结构，bone为材料科学领域的复合材料培训学生提供了一个有趣的论坛。 将继续开展教师研究经验（RET）和仿生材料推广计划（BMOP）等推广计划，其中包括对研究生，本科生和K-12水平的学生进行培训和推广。 还提出了一个新的推广计划，在该计划中，将向附近城市的水族馆提供公开讲座，向他们展示他们作为爱好而喜欢的无脊椎动物生物矿物（如海胆和软体动物贝壳）背后有趣的材料科学，以及这些生物矿物与脊椎动物生物矿物之间的相似性/差异，以展示仿生工程师如何开发新型分层结构复合材料。

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.