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      Real-Time Wireless Platform for In Vivo Monitoring of Bone Regeneration

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          Abstract

          For the monitoring of bone regeneration processes, the instrumentation of the fixation is an increasingly common technique to indirectly measure the evolution of bone formation instead of ex vivo measurements or traditional in vivo techniques, such as X-ray or visual review. A versatile instrumented external fixator capable of adapting to multiple bone regeneration processes was designed, as well as a wireless acquisition system for the data collection. The design and implementation of the overall architecture of such a system is described in this work, including the hardware, firmware, and mechanical components. The measurements are conditioned and subsequently sent to a PC via wireless communication to be in vivo displayed and analyzed using a developed real-time monitoring application. Moreover, a model for the in vivo estimation of the bone callus stiffness from collected data was defined. This model was validated in vitro using elastic springs, reporting promising results with respect to previous equipment, with average errors and uncertainties below 6.7% and 14.04%. The devices were also validated in vivo performing a bone lengthening treatment on a sheep metatarsus. The resulting system allowed the in vivo mechanical characterization of the bone callus during experimentation, providing a low-cost, simple, and highly reliable solution.

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          Most cited references62

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          Bone regeneration: current concepts and future directions

          Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. However, there are complex clinical conditions in which bone regeneration is required in large quantity, such as for skeletal reconstruction of large bone defects created by trauma, infection, tumour resection and skeletal abnormalities, or cases in which the regenerative process is compromised, including avascular necrosis, atrophic non-unions and osteoporosis. Currently, there is a plethora of different strategies to augment the impaired or 'insufficient' bone-regeneration process, including the 'gold standard' autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved 'local' strategies in terms of tissue engineering and gene therapy, or even 'systemic' enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis.
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            The biology of fracture healing.

            The biology of fracture healing is a complex biological process that follows specific regenerative patterns and involves changes in the expression of several thousand genes. Although there is still much to be learned to fully comprehend the pathways of bone regeneration, the over-all pathways of both the anatomical and biochemical events have been thoroughly investigated. These efforts have provided a general understanding of how fracture healing occurs. Following the initial trauma, bone heals by either direct intramembranous or indirect fracture healing, which consists of both intramembranous and endochondral bone formation. The most common pathway is indirect healing, since direct bone healing requires an anatomical reduction and rigidly stable conditions, commonly only obtained by open reduction and internal fixation. However, when such conditions are achieved, the direct healing cascade allows the bone structure to immediately regenerate anatomical lamellar bone and the Haversian systems without any remodelling steps necessary. In all other non-stable conditions, bone healing follows a specific biological pathway. It involves an acute inflammatory response including the production and release of several important molecules, and the recruitment of mesenchymal stem cells in order to generate a primary cartilaginous callus. This primary callus later undergoes revascularisation and calcification, and is finally remodelled to fully restore a normal bone structure. In this article we summarise the basic biology of fracture healing. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              Molecular mechanisms controlling bone formation during fracture healing and distraction osteogenesis.

              Fracture healing and distraction osteogenesis have important applications in orthopedic, maxillofacial, and periodontal treatment. In this review, the cellular and molecular mechanisms that regulate fracture repair are contrasted with bone regeneration that occurs during distraction osteogenesis. While both processes have many common features, unique differences are observed in the temporal appearance and expression of specific molecular factors that regulate each. The relative importance of inflammatory cytokines in normal and diabetic healing, the transforming growth factor beta superfamily of bone morphogenetic mediators, and the process of angiogenesis are discussed as they relate to bone repair. A complete summary of biological activities and functions of various bioactive factors may be found at COPE (Cytokines & Cells Online Pathfinder Encyclopedia), http://www.copewithcytokines.de/cope.cgi.
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                Author and article information

                Journal
                Sensors (Basel)
                Sensors (Basel)
                sensors
                Sensors (Basel, Switzerland)
                MDPI
                1424-8220
                15 August 2020
                August 2020
                : 20
                : 16
                : 4591
                Affiliations
                [1 ]Escuela Técnica Superior de Ingeniería, Universidad de Sevilla, 41092 Seville, Spain; jaime@ 123456us.es (J.D.); erreina@ 123456us.es (E.R.-R.)
                [2 ]Escuela Técnica Superior de Ingeniería, Universidad de Huelva, 21007 Huelva, Spain; msraya@ 123456diesia.uhu.es (M.S.-R.); juan.mora@ 123456dimme.uhu.es (J.M.-M.); jgalan@ 123456diesia.uhu.es (J.A.G.-G.)
                Author notes
                [* ]Correspondence: pbcarmona@ 123456us.es ; Tel.: +34-601-174-347
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-7605-5812
                https://orcid.org/0000-0001-6883-4317
                https://orcid.org/0000-0002-7997-9789
                https://orcid.org/0000-0003-1304-8372
                https://orcid.org/0000-0002-0491-7911
                https://orcid.org/0000-0002-5714-465X
                Article
                sensors-20-04591
                10.3390/s20164591
                7472372
                32824259
                a3ee18ed-45af-455e-894f-6c12efd556ec
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 July 2020
                : 14 August 2020
                Categories
                Article

                Biomedical engineering
                external fixator,wireless acquisition system,load sensor,bone regeneration,calibration,callus stiffness

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