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      A Review of the Impact of Implant Biomaterials on Osteocytes

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          Abstract

          In lamellar bone, a network of highly oriented interconnected osteocytes is organized in concentric layers. Through their cellular processes contained within canaliculi, osteocytes are highly mechanosensitive and locally modulate bone remodeling. We review the recent developments demonstrating the significance of the osteocyte lacuno-canalicular network in bone maintenance around implant biomaterials. Drilling during implant site preparation triggers osteocyte apoptosis, the magnitude of which correlates with drilling speed and heat generation, resulting in extensive remodeling and delayed healing. In peri-implant bone, osteocytes physically communicate with implant surfaces via canaliculi and are responsive to mechanical loading, leading to changes in osteocyte numbers and morphology. Certain implant design features allow peri-implant osteocytes to retain a less aged phenotype, despite highly advanced extracellular matrix maturation. Physicochemical properties of anodically oxidized surfaces stimulate bone formation and remodeling by regulating the expression of RANKL (receptor activator of nuclear factor–κB ligand), RANK, and OPG (osteoprotegerin) from implant-adherent cells. Modulation of certain osteocyte-related molecular signaling mechanisms (e.g., sclerostin blockade) may enhance the biomechanical anchorage of implants. Evaluation of the peri-implant osteocyte lacuno-canalicular network should therefore be a necessary component in future investigations of osseointegration to more completely characterize the biological response to materials for load-bearing applications in dentistry and orthopedics.

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          Most cited references54

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          Architecture of the osteocyte network correlates with bone material quality.

          In biological tissues such as bone, cell function and activity crucially depend on the physical properties of the extracellular matrix which the cells synthesize and condition. During bone formation and remodeling, osteoblasts get embedded into the matrix they deposit and differentiate to osteocytes. These cells form a dense network throughout the entire bone material. Osteocytes are known to orchestrate bone remodeling. However, the precise role of osteocytes during mineral homeostasis and their potential influence on bone material quality remains unclear. To understand the mutual influence of osteocytes and extracellular matrix, it is crucial to reveal their network organization in relation to the properties of their surrounding material. Here we visualize and topologically quantify the osteocyte network in mineralized bone sections with confocal laser scanning microscopy. At the same region of the sample, synchrotron small-angle X-ray scattering is used to determine nanoscopic bone mineral particle size and arrangement relative to the cell network. Major findings are that most of the mineral particles reside within less than a micrometer from the nearest cell network channel and that mineral particle characteristics depend on the distance from the cell network. The architecture of the network reveals optimization with respect to transport costs between cells and to blood vessels. In conclusion, these findings quantitatively show that the osteocyte network provides access to a huge mineral reservoir in bone due to its dense organization. The observed correlation between the architecture of osteocyte networks and bone material properties supports the hypothesis that osteocytes interact with their mineralized vicinity and thus, participate in bone mineral homeostasis.
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            The organization of the osteocyte network mirrors the extracellular matrix orientation in bone.

            Bone is a dynamic tissue that is continually undergoing a process of remodeling - an effect due to the interplay between bone resorption by osteoclasts and bone formation by osteoblasts. When new bone is deposited, some of the osteoblasts are embedded in the mineralizing collagen matrix and differentiate to osteocytes, forming a dense network throughout the whole bone tissue. Here, we investigate the extent to which the organization of the osteocyte network controls the collagen matrix arrangement found in various bone tissues. Several tissue types from equine, ovine and murine bone have been examined using confocal laser scanning microscopy as well as polarized light microscopy and back-scattered electron imaging. From comparing the spatial arrangements of unorganized and organized bone, we propose that the formation of a highly oriented collagen matrix requires an alignment of osteoblasts whereby a substrate layer provides a surface such that osteoblasts can align and, collectively, build new matrix. Without such a substrate, osteoblasts act isolated and only form matrices without long range order. Hence, we conclude that osteoblasts synthesize and utilize scaffold-like primary tissue as a guide for the deposition of highly ordered and mechanically competent bone tissue by a collective action of many cells. Copyright © 2010 Elsevier Inc. All rights reserved.
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              3D printed Ti6Al4V implant surface promotes bone maturation and retains a higher density of less aged osteocytes at the bone-implant interface

              For load-bearing orthopaedic applications, metal implants having an interconnected pore structure exhibit the potential to facilitate bone ingrowth and the possibility for reducing the stiffness mismatch between the implant and bone, thus eliminating stress-shielding effects. 3D printed solid and macro-porous Ti6Al4V implants were evaluated after six-months healing in adult sheep femora. The ultrastructural composition of the bone-implant interface was investigated using Raman spectroscopy and electron microscopy, in a correlative manner. The mineral crystallinity and the mineral-to-matrix ratios of the interfacial tissue and the native bone were found to be similar. However, lower Ca/P ratios, lower carbonate content, but higher proline, phenylalanine and tyrosine levels indicated that the interfacial tissue remained less mature. Bone healing was more advanced at the porous implant surface (vs. the solid implant surface) based on the interfacial tissue ν1 CO3(2-)/ν2 PO4(3-) ratio, phenylalanine and tyrosine levels approaching those of the native bone. The mechanosensing infrastructure in bone, the osteocyte lacuno-canalicular network, retained ∼40% more canaliculi per osteocyte lacuna, i.e., a 'less aged' morphology at the interface. The osteocyte density per mineralised surface area was ∼36-71% higher at the interface after extended healing periods.
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                Author and article information

                Journal
                J Dent Res
                J. Dent. Res
                JDR
                spjdr
                Journal of Dental Research
                SAGE Publications (Sage CA: Los Angeles, CA )
                0022-0345
                1544-0591
                04 June 2018
                August 2018
                : 97
                : 9
                : 977-986
                Affiliations
                [1 ]Department of Biomaterials, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
                Author notes
                [*]F.A. Shah, Department of Biomaterials, Sahlgrenska Academy, University of Gothenburg, Box 412, Göteborg, 405 30, Sweden. Email: furqan.ali.shah@ 123456biomaterials.gu.se
                Author information
                https://orcid.org/0000-0002-9876-0467
                https://orcid.org/0000-0003-3910-6665
                https://orcid.org/0000-0002-6974-2577
                Article
                10.1177_0022034518778033
                10.1177/0022034518778033
                6055115
                29863948
                f86f812f-d70f-4910-92de-8618a9370362
                © International & American Associations for Dental Research 2018

                This article is distributed under the terms of the Creative Commons Attribution 4.0 License ( http://www.creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Funding
                Funded by: Dr. Felix Neubergh Foundation, ;
                Funded by: IngaBritt och Arne Lundbergs Forskningsstiftelse, FundRef https://doi.org/10.13039/501100003849;
                Funded by: Stiftelsen Promobilia, FundRef https://doi.org/10.13039/100009389;
                Funded by: Stiftelsen Handlanden Hjalmar Svenssons, FundRef https://doi.org/10.13039/501100003744;
                Funded by: Stiftelserna Wilhelm och Martina Lundgrens, FundRef https://doi.org/10.13039/501100003745;
                Funded by: Vetenskapsrådet, FundRef https://doi.org/10.13039/501100004359;
                Award ID: K2015-52X-09495-28-4
                Categories
                Reviews
                Critical Reviews in Oral Biology & Medicine

                osseointegration,bone,dental implants,bone matrix,biocompatible materials,bone-implant interface

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