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

知识专长：羟基磷灰石（HA）是一种磷酸钙矿物，类似于骨的天然矿物磷灰石相，广泛用于制造支架，以支持植入骨移植物中的骨细胞生长。 该提案探讨了以下假设：在设计用作骨移植物的HA材料中，较小的晶粒尺寸和由热膨胀各向异性（TEA）引起的微裂纹（1）增加了粘附在移植物上的成骨细胞（骨形成）的数量和成熟，（2）促进矿化组织的沉积和微裂纹愈合，以及（3）促进了移植物的机械强度和性能的改善。 这些假设与已发表的初步实验室研究结果一致，这些研究结果明确确定了HA中的微裂纹，假设微裂纹是脆性陶瓷（如HA）的增韧机制，证明HA增强了成骨细胞功能，并显示纳米颗粒HA上的成骨细胞增殖增加。 本课题的研究目的有三：（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HA上成骨细胞微裂纹愈合的局部发生，并将这种愈合与整体和局部材料特性（如弹性模量）的可测量变化相关联。(3)确定晶界在成骨细胞附着和成熟中的作用，并将成骨细胞活性与晶粒尺寸相关联。 更广泛的影响： 在美国每年进行大约500，000例骨移植。 骨移植材料（自体移植物和同种异体移植物）的常见来源受到可用性、数量、不良机械性能、疾病传播风险和成本的高度限制。 迫切需要具有足够的机械完整性和增强的愈合/骨整合特性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，将成为目前所有可用移植材料的可行合成替代品，用于修复受损骨组织。 该项目将支持两名研究生在整个博士培训。 PI经常支持本科研究工作者的项目，其中许多人是期刊文章和会议报告的合著者。 研究小组的成员将参加每年夏天在密歇根州立大学夏季高中工程学院为底特律地区的学生，其中包括许多妇女和少数民族的参与者。

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.