Bone hierarchical organization through the lens of materials science: Present opportunities and future challenges.

Multiscale characterization is essential to better understand the hierarchical architecture of bone and an array of analytical methods contributes to exploring the various structural and compositional aspects. Incorporating X-ray tomography, X-ray scattering, vibrational spectroscopy, and atom probe tomography alongside electron microscopy provides a comprehensive approach, offering insights into the diverse levels of organization within bone. X-ray scattering techniques reveal information about collagen-mineral spatial relationships, while X-ray tomography captures 3D structural details, especially at the microscale.

Mesoscale characterization of osseointegration around an additively manufactured genistein-coated implant.

Given the hierarchical nature of bone and bone interfaces, osseointegration, namely the formation of a direct bone-implant contact, is best evaluated using a multiscale approach. However, a trade-off exists between field of view and spatial resolution, making it challenging to image large volumes with high resolution. In this study, we combine established electron microscopy techniques to probe bone-implant interfaces at the microscale and nanoscale with plasma focused ion beam-scanning electron microscopy (PFIB-SEM) tomography to evaluate osseointegration at the mesoscale.

Effect of plate orientation on apparent thickness of mineral plates by transmission electron microscopy.

Purpose: Transmission electron microscopy (TEM) is widely used to study the ultrastructure of bone. The mineral of bone occurs as polycrystalline mineral plates about 3 to 6 nm in thickness. A problem in using TEM to make quantitative analyses of bone is that the orientation of the plates with respect to the plane of the section being imaged is expected to affect their apparent thickness.

Ultrastructure and Nanoporosity of Human Bone Shown with Correlative On-Axis Electron and Spectroscopic Tomographies.

Mineralized collagen fibrils are the building block units of bone at the nanoscale. While it is known that collagen fibrils are mineralized both inside their gap zones (intra-fibrillar mineralization) and on their outer surfaces (extra-fibrillar mineralization), a clear visualization of this architecture in three dimensions (3D), combining structural and compositional information over large volumes, but without compromising the resolution, remains challenging. In this study, we demonstrate the use of on-axis -contrast electron tomography (ET) with correlative energy-dispersive X-ray spectroscopy (EDX) tomography to examine rod-shaped samples with diameters up to 700 nm prepared from individual osteonal lamellae in the human femur.

Bone structure and composition in a hyperglycemic, obese, and leptin receptor-deficient rat: Microscale characterization of femur and calvarium.

Metabolic abnormalities, such as diabetes mellitus and obesity, can impact bone quantity and/or bone quality. In this work, we characterize bone material properties, in terms of structure and composition, in a novel rat model with congenic leptin receptor (LepR) deficiency, severe obesity, and hyperglycemia (type 2 diabetes-like condition). Femurs and calvaria (parietal region) from 20-week-old male rats are examined to probe bones formed both by endochondral and intramembranous ossification.

Multimodal and Multiscale Characterization of the Bone-Bacteria Interface in a Case of Medication-Related Osteonecrosis of the Jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is a known side effect of bisphosphonates (BPs). Although bacterial infection is usually present, the etiology of MRONJ remains unknown. Here we apply a multimodal and multiscale (micro-to-nano) characterization approach to investigate the interface between necrotic bone and bacteria in MRONJ.

Atom probe tomography for biomaterials and biomineralization.

Biominerals and biomaterials are part of our daily lives, from our skeleton and teeth to coral reefs and carbon-capturing single-cell organisms in the oceans, to engineered ceramics comprising our toothpaste and bone replacements. Many biominerals are hierarchically structured with remarkable material properties that arise from their unique combination of organic and inorganic components. Such structural hierarchy is often formed through a process of biomineralization.

PTH 1-34-functionalized bioactive glass improves peri-implant bone repair in orchiectomized rats: Microscale and ultrastructural evaluation.

The objective of this work was to investigate the use of Biogran® functionalized with parathyroid hormone (PTH) 1-34 by sonochemistry for the local delivery of this anabolic agent to the implant site. The effects of Biogran® and topical administration of PTH 1-34 on peri-implant bone regeneration were evaluated from the microscale to ultrastructural levels in healthy (SHAM) and orchiectomized (ORQ). While some animals only received a titanium implant in their tibial metaphyses (CLOT group), in others the peri-implant defect was first filled with Biogran® either without or with PTH 1-34 functionalization (BG and BGPTH groups, respectively) prior to implant installation.

Bone without borders - Monetite-based calcium phosphate guides bone formation beyond the skeletal envelope.

Calcium phosphates (CaP) represent an important class of osteoconductive and osteoinductive biomaterials. As proof-of-concept, we show how a multi-component CaP formulation (monetite, beta-tricalcium phosphate, and calcium pyrophosphate) guides osteogenesis beyond the physiological envelope. In a sheep model, hollow dome-shaped constructs were placed directly over the occipital bone.

Bone mineral organization at the mesoscale: A review of mineral ellipsoids in bone and at bone interfaces.

Much debate still revolves around bone architecture, especially at the nano- and microscale. Bone is a remarkable material where high strength and toughness coexist thanks to an optimized composition of mineral and protein and their hierarchical organization across several distinct length scales. At the nanoscale, mineralized collagen fibrils act as building block units.

From tissue retrieval to electron tomography: nanoscale characterization of the interface between bone and bioactive glass.

The success of biomaterials for bone regeneration relies on many factors, among which osseointegration plays a key role. Biogran (BG) is a bioactive glass commonly employed as a bone graft in dental procedures. Despite its use in clinical practice, the capability of BG to promote osseointegration has never been resolved at the nanoscale.

Three-Dimensional Insights into Interfacial Segregation at the Atomic Scale in a Nanocrystalline Glass-Ceramic.

The distribution of dopant atoms plays a key role in the effectiveness of doping, thereby requiring delicate characterizations. In this study, we found that energy-dispersive X-ray spectroscopy (EDX) and electron energy loss spectroscopy (EELS) techniques in scanning transmission electron microscopy (STEM) were not adequate to reveal the distribution of yttrium and the chemical composition of the ZrO/SiO heterophase interface in an yttrium-doped ZrO-SiO nanocrystalline glass-ceramic. Atom probe tomography (APT) is rarely utilized to characterize ceramics due to some inherent difficulties.

Ti-5Al-5Mo-5V-3Cr bone implants with dual-scale topography: a promising alternative to Ti-6Al-4V.

Modifications to the compositional, topographical and morphological aspects of bone implants can lead to improved osseointegration, thus increasing the success of bone implant procedures. This study investigates the creation of dual-scale topography on Ti-5Al-5Mo-5V-3Cr (Ti5553), an alloy not presently used in the biomedical field, and compares it to Ti-6Al-4V (Ti64), the most used Ti alloy for bone implants. Dual-scale surface topography was obtained by combining selective laser melting (SLM) and electrochemical anodization, which resulted in micro- and nanoscale surface features, respectively.