FRG: FRG on Microcracking in Hydroxyapatite and the Implications for Bone Tissue Engineering

智力优势：羟基磷灰石(HA)是一种类似于骨的天然矿物磷灰石相的磷酸钙矿物，广泛用于构建支架以支持植入的骨移植中的骨细胞生长。这一建议探索了一种假设，即用于骨移植的HA材料中由于热膨胀各向异性(TEA)而导致的较小的颗粒尺寸和微裂纹：(1)增加附着在移植物上的成骨(骨形成)细胞的数量和成熟度；(2)促进矿化组织的沉积和微裂纹的愈合；(3)促进移植物的机械强度和性能的改善。这些假设与已发表的和初步的实验室研究结果一致，这些结果明确地确定了HA中的微裂纹，假设微裂纹是HA等脆性陶瓷的增韧机制，表明HA增强了成骨细胞的功能，并显示在纳米颗粒HA上促进了成骨细胞的增殖。该项目有三个目标：(1)确定HA中微裂纹的损伤程度，并将微裂纹与成骨细胞的附着和成熟联系起来。(2)确定成骨细胞在HA上局部发生微裂纹愈合，并将这种愈合与可测量的整体和局部材料性质的变化(如弹性模数)相关联。(3)探讨晶界在成骨细胞附着和成熟中的作用，以及成骨细胞活性与颗粒大小的关系。更广泛的影响：美国每年大约进行500,000例骨移植。骨移植材料的常见来源，无论是自体移植还是同种异体移植，都受到可获得性、数量、机械性能差、疾病传播风险和成本的高度限制。迫切需要一种具有足够机械完整性和增强愈合/骨整合性能的生物相容性合成工程化骨移植材料。预期在该项目中开发的Neobone生物陶瓷结构，由于其改善的形态和细胞活性，将成为修复受损骨组织的所有现有移植材料的可行的合成替代品。该项目将支持两名研究生完成他们的博士培训。PI经常支持本科生研究人员的项目，其中许多人是期刊文章和会议演示文稿的合著者。研究团队的成员每年夏天都会参加密歇根州立大学为底特律地区学生设立的夏季高中工程学院，其中包括许多女性和少数族裔参与者。

INTELLECTUAL MERIT: Hydroxyapatite (HA) is a calcium phosphate mineral resembling the natural mineral apatite phase of bone and widely used to fabricate scaffolds to support bone cell growth in implanted bone grafts. This proposal explores the hypothesis that smaller grain sizes and microcracking caused by thermal expansion anisotropy (TEA) in HA materials designed for use as bone grafts (1) increase the number and maturation of osteoblast (bone forming) cells adhering to the graft, (2) foster deposition of mineralized tissue and microcrack healing, and (3) promote improved mechanical strength and performance of the graft. These hypotheses are consistent with published and preliminary laboratory findings that definitively identified microcracking in HA, postulated microcracking as a toughening mechanism for brittle ceramics such as HA, demonstrated that HA enhances osteoblast function, and showed increased osteoblast proliferation on nanograined HA. The project has three objectives: (1) To determine the extent of microcrack damage in HA and correlate the microcracking with osteoblast attachment and maturation. (2) To determine the localized occurrence of microcrack healing by osteoblasts on HA and correlate such healing with measurable changes in global and local material properties such as the elastic modulus. (3) To determine the role of grain boundaries on osteoblast attachment and maturation and correlate osteoblast activity with grain size. BROADER IMPACTS: Approximately 500,000 bone grafts are performed in the United States annually. Common sources for bone graft material, both autografts and allografts, are highly limited by availability, quantity, poor mechanical properties, risk of disease transmission, and cost. There is an urgent need for a biocompatible synthetic engineered bone graft material with adequate mechanical integrity and enhanced healing/bone integration properties. The expectation is that the neobone bioceramic constructs developed in this project, because of their improved morphology and cellular activity, will be a viable synthetic alternative to all currently available graft materials for repair of damaged bone tissue. The project will support two graduate students throughout their doctoral training. The PIs have routinely supported undergraduate research workers on their projects, many of whom have been coauthors on journal articles and conference presentations. Members of the research team will participate each summer in the MSU Summer High School Engineering Institute for Detroit-area students, who include many women and minority participants.