Biology subjects

Weinkamer, R.

Publications and source records attributed to Weinkamer, R..

6 recordsLinked to original sources

bioRxiv2026

Aging modifies microstructure and material properties of mineralized cartilage and subchondral bone in the murine knee

The osteochondral junction is a specialized region ensuring the biomechanical and biological integration of the unmineralized articular cartilage with the subchondral bone through an intermediate layer of mineralized cartilage. This location is of clinical relevance, being the target of osteoarthritis. While aging is considered a risk factor for osteoarthritis, the interplay between microstructural and material changes during aging and predisposing to joint degeneration is not fully clear. This is especially true for mineralized cartilage, which remains understudied despite its critical role in load transfer from unmineralized articular cartilage to bone. We investigate age-related alterations of mineralized cartilage and subchondral bone in rat tibiae of adult and aged animals using a multimodal, high-resolution, correlative analysis. Our approach includes micro-computed tomography to measure microstructural features, second harmonic generation imaging to visualize collagen organization, quantitative backscattered electron imaging to map local mineral content, and nanoindentation to obtain mechanical properties. Mineralized cartilage and subchondral bone exhibited distinct age-related modifications. At the architectural level, the subchondral plate thickened and the trabecular network became coarser, those changes being different from those observed in the metaphysis. At the tissue level, mineralized cartilage was less mineralized than bone but exhibits a greater relative increase of mineral content with age, underlying differences in mineralization. A central observation is that aging led to an abrupt transition in mineral content and mechanical properties across the interface between unmineralized and mineralized cartilage, with a conceivable impact on stress localization. Overall, these changes may alter load transfer and contribute to age-related joint degeneration.

bioengineering↗

bioRxiv2025

Cement lines are stiffer and harder than bone but exhibit different mineral-mechanics relationships due to thicker and shorter mineral particles

The remarkable mechanical performance of bone arises from its complex hierarchical structure and from the presence of numerous internal interfaces joining the different components. Formed during bone remodeling, the cement line (CL) is a thin interface surrounding osteons. Although often neglected due to its small size, the CL has been suggested to play an important role in bone fracture toughness. However, there is an ongoing debate about its specific structure and mechanical behavior. Here, we investigate the composition-mechanics relationship at the CL and surrounding bone in human osteons using multiple methods in a correlative manner. We found that the CL is stiffer and harder than adjacent osteonal tissue. However, the CL requires more mineral than bone to attain the same stiffness and hardness. Analyzing the nanoscale properties of the mineral, we found thicker but shorter particles at the CL. Using a mechanical model, we interpreted the lower aspect ratio of the mineral particles as a less effective way to reinforce the collagen matrix. Casting our findings into a computational model, we questioned the possible protective role of the CL, which is not a soft interface as traditionally believed.

bioengineering↗

bioRxiv2024

The mineralization of osteonal cement line depends on where the osteon is formed

The cement line (CL) is a thin layer separating secondary osteons from interstitial bone and other osteons. It is assumed to play a significant role in bone fracture resistance, owing to its ability to deflect or arrest microcracks. Despite the possible role for bone quality, the CL is still one of the least understood microstructural features of bones, with unknowns on CL composition, mineralization, and mechanical properties. This study, focusing on CL mineralization, aims to elucidate the interplay between the mineral content of the CL and of adjacent bone tissue. Using quantitative backscattered electron imaging, osteons with different degrees of mineralization coming from human femoral samples were analyzed. We implemented a spatially resolved analysis of the mineral content in layers along the CL, considering both regions inside the osteon (i.e., formed soon after CL deposition) and outside (i.e., already present at the time of CL deposition). We found that the mineral content of the CL correlates strongly with the mineral content outside of the osteon, but not inside. Assuming the mineral content of the osteon as a proxy of its age, we demonstrate that not only the osteon, but also the CL increases its mineral content with time. However, the rate of increase is lower in the CL. Importantly, the specific value of the high initial mineral content of the CL depends on the mineral content of the local surrounding, in which the osteon was formed. Our findings highlight the central role of the local degree of mineralization of the bone around the osteon for building the CL.

bioengineering↗

bioRxiv2023

Logistics of Bone Mineralization in the Chick Embryo Studied by 3D Cryo FIB-SEM Imaging

During skeletal development, bone growth and mineralization require transport of substantial amounts of calcium, while maintaining very low concentration. How an organism overcomes this major logistical challenge remains mostly unexplained. To shed some light on the dynamics of this process, we use cryogenic Focused Ion Beam-Scanning Electron Microscopy (cryo-FIB/SEM) to image forming bone tissue at day 13 of a chick embryo femur. We visualize both cells and matrix in 3D and observe calcium-rich intracellular vesicular structures. Counting the number of these vesicles per unit volume and measuring their calcium content based on the electron back-scattering signal, we are able to estimate the intracellular velocity at which these vesicles need to travel to transport all the calcium required for the mineral deposited in one day within the collagenous tissue. We estimate this velocity at 0.27 m/s, which is too large for a diffusion process and rather suggests active transport through the cellular network. We conclude that calcium logistics is hierarchical and based on several transport mechanisms: first through the vasculature using calcium-binding proteins and the blood flow, then active transport over tens of micrometers through the network of osteoblasts and osteocytes and, finally, diffusive transport over the last one or two microns.

systems biology↗

bioRxiv2020

Three-dimensional interrelationship between osteocyte network and forming mineral during human bone remodeling

During bone remodeling, osteoblasts are known to deposit unmineralized collagenous tissue (osteoid), which mineralizes after some time lag. Some of the osteoblasts differentiate into osteocytes, forming a cell network within the lacunocanalicular network (LCN) of bone. To get more insight into the potential role of osteocytes in the mineralization process of osteoid, sites of bone formation were three-dimensionally imaged in nine forming human osteons using focused ion beam-scanning electron microscopy (FIB-SEM). In agreement with previous observations, the mineral concentration was found to gradually increase from the central Haversian canal towards preexisting mineralized bone. Most interestingly, a similar feature was discovered on a length scale more than 100-times smaller, whereby mineral concentration increased from the LCN, leaving around the canaliculi a zone virtually free of mineral, the size of which decreases with progressing mineralization. This suggests that the LCN controls mineral formation but not just by diffusion of mineralization precursors, which would lead to a continuous decrease of mineral concentration from the LCN. Our observation is, however, compatible with the codiffusion and reaction of precursors and inhibitors from the LCN into the bone matrix.

biophysics↗

bioRxiv2020

Mineral density differences between femoral cortical bone and trabecular bone are not explained by turnover rate alone

Bone mineral density distributions (BMDDs) are a measurable property of bone tissues that depends strongly on bone remodelling and mineralisation processes. These processes can vary significantly in health and disease and across skeletal sites, so there is high interest in analysing these processes from experimental BMDDs. Here, we propose a rigorous hypothesis-testing approach based on a mathematical model of mineral heterogeneity in bone due to remodelling and mineralisation, to help explain differences observed between the BMDD of human femoral cortical bone and the BMDD of human trabecular bone. Recent BMDD measurements show that femoral cortical bone possesses a higher bone mineral density, but a similar mineral heterogeneity around the mean compared to trabecular bone. By combining this data with the mathematical model, we are able to test whether this difference in BMDD can be explained by (i) differences in turnover rate; (ii) differences in osteoclast resorption behaviour; and (iii) differences in mineralisation kinetics between the two bone types. We find that accounting only for differences in turnover rate is inconsistent with the fact that both BMDDs have a similar spread around the mean, and that accounting for differences in osteoclast resorption behaviour leads to biologically inconsistent bone remodelling patterns. We conclude that the kinetics of mineral accumulation in bone matrix must therefore be different in femoral cortical bone and trabecular bone. Although both cortical and trabecular bone are made up of lamellar bone, the different mineralisation kinetics in the two types of bone point towards more profound structural differences than usually assumed.

biophysics↗