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.
Approximately 500,000 bone grafts are performed annually in the U.S. With the aging of the baby-boom generation, advancements in bone graph materials will become more necessary as patients demand a more active lifestyle. Autografts and allografts are common sources for bone grafts but are limited by availability, quantity, disease, mechanical reliability, and cost. Thus, there is a need for a biocompatible synthetic bone graft material with enhanced healing/bone integration. Hydroxyapatite (HA), a biocompatible bone graft material, is the primary mineral in natural bone that enhances bone repair. Bone fractures heal at the site of the bone microfractures or microcracks. So, to fabricate better synthetic HA bone replacement materials, it is important to understand and exploit links between microcracking and bone healing. In comparing uncracked HA to microcracked HA samples, we found that microcracked HA promoted significantly faster early bone forming cell attachment and by 21 days, faster bone mineralization. Bone cells concentrated at the crack tips and, with time, moved to fill in the crack itself. This more rapid cell response to microcracked HA was found to coincide with a release of calcium ions from the HA scaffold, where calcium is known to promote bone cell activity. We also examined the effect of microcracks on bone resorbing cells, finding less sensitivity of these cells to the presence of the cracks. We also examined the mechanical behavior of the HA samples finding that the Weibull modulus, m, is an important gauge of mechanical reliability. We developed a single mathematical form to describe how porosity influences fracture strength and stiffness. This result points to the inter-relationships between different mechanical properties that were not previously reported and which may now be exploited to develop new porous HA and other brittle materials. Weibull modulus data for highly porous materials are sparse in the literature. No other studies except the earlier work on this grant include a systematic examination of the Weibull modulus for a material with a high volume fraction of porosity. Determining the fracture strength and Weibull modulus of HA for such porous ceramics will aid the design and guide the possible application of high porosity components such as sensors and filters (including biomedical filters). We characterized microcrack damage for a variety of brittle ceramics which may provide a means for characterizing microcrack damage in both biomedical and non-biomedical materials. This work was recognized as a finalist for the inaugural Cahn prize, awarded annually by the Journal of Materials Science. Microcracks induced by Vickers indentation are frequently used as model cracks in microcracking studies since the number, location, and length of such microcracks can be controlled. While most slow crack growth studies in the literature are carried out after aging, this study focuses on slow crack growth during aging in ambient air for indentation-induced radial cracks in 94% dense HA. Results from our study suggest that the slow growth of radial cracks is a load dependent process, which has not been reported previously in the literature. It is important to note that the dissipation of residual strain energy can take the form of both radial crack (cracking) and lateral crack (chipping, spalling or flaking) propagation. Thus when using radial crack as the model crack in bioceramics for in vitro cell studies, the slow growth of radial cracks during aging and the disturbance from lateral cracks should be treated carefully.
