(From left) Photo of bone defect and implanted scaffold in sheep’s tibia bone. Reproduced from J.J. Li, et al. A novel bone substitute with high bioactivity, strength, and porosity for repairing large and load-bearing bone defects. Adv. Healthc. Mater., 8 (8) (2019), Article 1801298. Reconstructed atom maps for in vivo bone tissue formed in a bioceramic scaffold showing 1D concentration profile in detail.The atomic-scale composition of bone growing in a bioceramic scaffold has been revealed for the first time using an atom probe [Holmes et al., Acta Biomaterialia 162 (2023) 199-210, https://doi.org/10.1016/j.actbio.2023.02.039]. Bone damaged, by injury or disease, can be repaired using autographs or synthetic bone substitutes. But key to the success of synthetic substitutes is facilitating tissue regrowth at the interface, about which relatively little is known.
“We wanted to understand the structure and composition of bone tissue at the atomic scale, and how this varies between newly formed bone tissue and mature cortical bone tissue,” explain Hala Zreiqat (School of Biomedical Engineering) and Natalie Holmes of the University of Sydney. “We wanted to track the bioceramic implant degradation and diffusion into the surrounding biological tissue.”
Bone is a complex, hierarchical material consisting of an organic phase made of type-1 collagen fibers and fibrils, which give bone the ability to deform without cracking, interspersed with hydroxyapatite crystals, which provide rigidity and hardness. Synthetic bone scaffolds to support regrowing tissue tend to be made from bioceramics such as bioactive glass, which actively bonds to bone and releases ions during degradation that stimulate biological responses associated with osteogenesis and blood vessel formation. Understanding exactly how scaffold materials interact with bone on an atomic scale is essential to their development as an effective treatment.
Atom probe tomography (APT) can provide atomic-scale elemental information about organic and inorganic materials by using a strong electrostatic field to field-evaporate the atoms from the apex of needle-shapes samples. The technique produces a three-dimensional picture of the distribution of elements within the sample at the nanoscale.
“APT enabled us to determine the structure and composition of bone tissue and degraded bioceramic implant on the atomic scale,” Holmes and Zreiqat point out. “Supported by a complimentary technique - nanoSIMS (nanoscale secondary ion mass spectrometry), [we] imaged the structure and composition of the bone tissue, implant, and interface on the nanoscale.”
The APT analysis, led by Julie Cairney and Holmes using the University of Sydney’s one-of-a-kind atom probe facility at cryogenic temperatures, ultrahigh vacuum, and high voltage, reveals that newly formed bone is different in composition to mature cortical bone. Elements from the degrading scaffold, in particular Al, are also found in newly formed and in the mature original bone.
“This knowledge will help us to map the formation of new bone tissue and inform future synthetic bone (bioceramic implant) medical device design, providing the basis for improved rational design of bioceramic bone implants,” adds Zreiqat.