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

知识优势：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的骨细胞生长。本研究提出了以下假设：用于骨移植物的透明质酸材料中，由于热膨胀各向异性（TEA）导致的晶粒尺寸减小和微裂纹(1)增加了附着在移植物上的成骨细胞（骨形成）的数量和成熟，(2)促进矿化组织沉积和微裂纹愈合，(3)促进移植物机械强度和性能的提高。这些假设与已发表的和初步的实验室研究结果一致，这些研究结果明确地确定了透明质酸中的微开裂，假设微开裂是透明质酸等脆性陶瓷的增韧机制，证明了透明质酸增强了成骨细胞的功能，并显示出纳米颗粒透明质酸上成骨细胞的增殖增加。该项目有三个目标：(1)确定HA中微裂纹损伤的程度，并将微裂纹与成骨细胞附着和成熟联系起来。(2)确定成骨细胞在HA上局部发生的微裂纹愈合，并将这种愈合与整体和局部材料特性（如弹性模量）的可测量变化联系起来。(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大小联系起来。更广泛的影响：在美国，每年大约进行50万例骨移植手术。常见的骨移植材料来源，无论是自体骨移植还是同种异体骨移植，都受到可用性、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骨移植材料。期望在这个项目中开发的新骨酮生物陶瓷结构，由于其改进的形态和细胞活性，将成为一种可行的合成替代目前所有可用的移植材料，用于修复受损的骨组织。该项目将支持两名研究生的整个博士培训。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报告的合著者。研究小组的成员每年夏天将参加密歇根州立大学底特律地区学生暑期高中工程学院，其中包括许多女性和少数民族参与者。

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.