Heterogeneity of the osteocyte lacuno-canalicular network architecture and material characteristics across different tissue types in healing bone

Various tissue types, including fibrous connective tissue, bone marrow, cartilage, woven and lamellar bone coexist in healing bone. Similar to all bone tissue type, healing bone contains a lacuno-canalicular network (LCN) housing osteocytes that are known to orchestrate bone remodeling in healthy bone by sensing mechanical strains and translating them into biochemical signals. The structure of the LCN is also hypothesized to influence mineralization processes. Hence, the aim of the present study was to visualize and correlate spatial variations in the LCN topology with mineral characteristics, within and at the interfaces of the different tissue types that comprise healing bone. We applied a correlative multi-method approach to visualize the LCN architecture and quantify mineral particle size and orientation within healing femoral bone in a mouse osteotomy model (26 weeks old C57BL/6 mice). This approach revealed structural differences across several length scales during endochondral ossification within the following regions: calcified cartilage, bony callus, cortical bone and the transition zone between the cortical region and callus that developed during 21 days after the osteotomy. In this transition zone, we observed a continuous convergence of mineral characteristics and osteocyte lacunae shape as well as discontinuities in the lacunae volume and LCN connectivity. The bony callus exhibits a 34% higher lacunae number density with 40% larger lacunar volume compared to cortical bone. The presented correlations between LCN architecture and mineral characteristics improves our understanding of how bone develops during healing and may indicate a contribution of osteocytes to bone (re)modeling

Ptychographic X-ray nanotomography quantifies mineral distributions in human dentine

Bones are bio-composites with biologically tunable mechanical properties, where a polymer matrix of nanofibrillar collagen is reinforced by apatite mineral crystals. Some bones, such as antler, form and change rapidly, while other bone tissues, such as human tooth dentine, develop slowly and maintain constant composition and architecture for entire lifetimes. When studying apatite mineral microarchitecture, mineral distributions or mineralization activity of bone-forming cells, representative samples of tissue are best studied at submicrometre resolution while minimizing sample-preparation damage. Here, we demonstrate the power of ptychographic X-ray tomography to map variations in the mineral content distribution in three dimensions and at the nanometre scale. Using this non-destructive method, we observe nanostructures surrounding hollow tracts that exist in human dentine forming dentinal tubules. We reveal unprecedented quantitative details of the ultrastructure clearly revealing the spatially varying mineralization density. Such information is essential for understanding a variety of natural and therapeutic effects for example in bone tissue healing and ageing

Nanocrystal residual strains and density layers enhance failure resistance in the cleithrum bone of evolutionary advanced pike fish

Failure resistant designs are particularly crucial for bones subjected to rapid loading, as is the case for the ambush hunting northern pike Esox lucius . These fish have slim and low density osteocyte lacking bones. As part of the swallowing mechanism, the cleithrum bone opens and closes the jaw. The cleithrum needs sufficient strength and damage tolerance, to withstand years of repetitive rapid gape and suck cycles of feeding. The thin wing shaped bone comprises anisotropic layers of mineralized collagen fibers that exhibit periodic variations in mineral density on the mm and micrometer length scales. Wavy collagen fibrils interconnect these layers yielding a highly anisotropic structure. Hydrated cleithra exhibit Young s moduli spanning 3 9 GPa where the yield stress of amp; 8764;40 MPa increases markedly to exceed amp; 8764;180 MPa upon drying. This 5x observation of increased strength corresponds to a change to brittle fracture patterns. It matches the emergence of compressive residual strains of amp; 8764;0.15 within the mineral crystals due to forces from shrinking collagen layers. Compressive stresses on the nanoscale, combined with the layered anisotropic microstructure on the mm length scale, jointly confer structural stability in the slender and lightweight bones. By employing a range of X ray, electron and optical imaging and mechanical characterization techniques, we reveal the structure and properties that make the cleithra impressively damage resistant composite

Developing consensus on core outcome sets of domains for acute, the transition from acute to chronic, recurrent/episodic, and chronic pain: results of the INTEGRATE-pain Delphi process

This is the final version. Available on open access from Elsevier via the DOI in this recordData sharing statement: Individual participant data that was collected throughout the research process from Delphi participants is not available to others. De-identified participant data was aggregated for analysis and presented in an anonymized format through tables in the article and supplement. All other research data is unavailable.Background: Pain is the leading cause of disability worldwide among adults and effective treatment options remain elusive. Data harmonization efforts, such as through core outcome sets (COS), could improve care by highlighting cross-cutting pain mechanisms and treatments. Existing pain-related COS often focus on specific conditions, which can hamper data harmonization across various pain states. Methods: Our objective was to develop four overarching COS of domains/subdomains (i.e., what to measure) that transcend pain conditions within different pain categories. We hosted a meeting to assess the need for these four COS in pain research and clinical practice. Potential COS domains/subdomains were identified via a systematic literature review (SLR), meeting attendees, and Delphi participants. We conducted an online, three step Delphi process to reach a consensus on domains to be included in the four final COS. Survey respondents were identified from the SLR and pain-related social networks, including multidisciplinary health care professionals, researchers, and people with lived experience (PWLE) of pain. Advisory boards consisting of COS experts and PWLE provided advice throughout the process. Findings: Domains in final COS were generally related to aspects of pain, quality of life, and physical function/activity limitations, with some differences among pain categories. This effort was the first to generate four separate, overarching COS to encourage international data harmonization within and across different pain categories. Interpretation: The adoption of the COS in research and clinical practice will facilitate comparisons and data integration around the world and across pain studies to optimize resources, expedite therapeutic discovery, and improve pain care. Funding: Innovative Medicines Initiative 2 Join Undertaking; European Union Horizon 2020 research innovation program, European Federation of Pharmaceutical Industries and Associations (EFPIA) provided funding for IMI-PainCare. RDT acknowledges grants from Esteve and TEVA.European Union Horizon 202

A transition from unimodal to multimodal activations in four sensory modalities in humans: an electrophysiological study

<p>Abstract</p> <p>Background</p> <p>To investigate the long-latency activities common to all sensory modalities, electroencephalographic responses to auditory (1000 Hz pure tone), tactile (electrical stimulation to the index finger), visual (simple figure of a star), and noxious (intra-epidermal electrical stimulation to the dorsum of the hand) stimuli were recorded from 27 scalp electrodes in 14 healthy volunteers.</p> <p>Results</p> <p>Results of source modeling showed multimodal activations in the anterior part of the cingulate cortex (ACC) and hippocampal region (Hip). The activity in the ACC was biphasic. In all sensory modalities, the first component of ACC activity peaked 30–56 ms later than the peak of the major modality-specific activity, the second component of ACC activity peaked 117–145 ms later than the peak of the first component, and the activity in Hip peaked 43–77 ms later than the second component of ACC activity.</p> <p>Conclusion</p> <p>The temporal sequence of activations through modality-specific and multimodal pathways was similar among all sensory modalities.</p