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      Can a Biodegradable Implanted Bilayered Drug Delivery System Loaded with BMP-2/BMP-12 Take an Effective Role in the Biological Repair Process of Bone–Tendon Injuries? A Preliminary Report

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          Abstract

          Background

          Use of biodegradable and biocompatible materials in the orthopedic surgery is gaining popularity. In this research, the rate of controlled release of a bilayered prototype biomaterial designed to promote osteoblastic and tenoblastic activity was calculated using pharmacochemical methods.

          Methods

          The first part of the design, composed of a sodium tetraborate, polyvinyl alcohol, and starch based hydrogel, was loaded with bone morphogenic protein-2. The second part which was composed of a sodium tetraborate, polyvinyl alcohol, and chitosan based hydrogel was loaded with bone morphogenic protein-12. Osteochondral and tendon tissue specimens were obtained from patients with a diagnosis of gonarthrosis and primary bone cells and tendon cells cultures were prepared following treatment with collagenase enzyme. Cell samples were collected from the groups by means of an invert light microscope and environmental scanning electron microscope underwent at the 1st and 21st days. The level of osteogenic differentiation was measured by the activity of alkaline phosphatase. For the statistical evaluation of the obtained data, groups were compared with post hoc Tukey test following analysis of variance. Level of significance was accepted to be <0,01.

          Results

          Both osteogenic and tenogenic stimulation were observed in the cultured specimens. In comparison to the control groups, the rate of proliferation of healthy cells was found to be higher in the groups to which the design was added ( p < 0.01).

          Conclusions

          Our research is a preliminary report that describes a study conducted in an in vitro experimental setting. We believe that such prototype systems may be pioneers in targeted drug therapies after reconstructional surgeries.

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          Most cited references43

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          The cell and molecular biology of fracture healing.

          Fracture healing is a complex physiologic process that involves the coordinated participation of several cell types. By using a reproducible model of experimental fracture healing in the rat, it is possible to elucidate the integrated cellular responses that signal the pathways and the role of the extracellular matrix components in orchestrating the events of fracture healing. Histologic characterization of fracture healing shows that intramembranous ossification occurs under the periosteum within a few days after an injury. Events of endochondral ossification occur adjacent to the fracture site and span a period of up to 28 days. Remodeling of the woven bone formed by intramembranous and endochondral ossification proceeds for several weeks. Spatial and temporal expression of genes for major collagens (Types I and II), minor fibrillar collagens (Types IV and XI), and several extracellular matrix components (osteocalcin, osteonectin, osteopontin, fibronectin and CD44) are detected by in situ hybridization. Immunohistochemical studies show that expression of proliferating cell nuclear antigen is both time and space dependent and differentially expressed in the callus tissues formed by the intramembranous and endochondral processes. Chondrocytes involved in endochondral ossification undergo apoptosis (programmed cell death), and early events in fracture healing may be initiated by the expression of early response genes such as c-fos. Additional characterization and elucidation of fracture healing will lay the foundation for subsequent studies aimed at identifying mechanisms for enhancing skeletal repair.
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            Platelet-Rich Plasma Intra-articular Knee Injections Show No Superiority Versus Viscosupplementation: A Randomized Controlled Trial.

            Osteoarthritis (OA) is a common disease that will affect almost half the population at some point in their lives through pain and decreased functional capacity. New nonoperative options are being proposed to treat earlier stages of joint degeneration to provide symptomatic relief and delay surgical intervention.
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              Platelet-rich plasma in rotator cuff repair: a prospective randomized study.

              Although platelet-rich plasma (PRP) has been used in rotator cuff repair, most authors have been unable to report the advantages of this method in clinical trials. The use of PRP promotes better functional and structural results in arthroscopic rotator cuff repair. Randomized controlled trial; Level of evidence, 1. This was a prospective, randomized, double-blind study with 2 groups of 27 patients each (PRP group and control group). Complete supraspinatus tears with retraction of less than 3 cm were subjected to arthroscopic single-row repair; at the end of the surgical procedure, liquid PRP prepared by apheresis was given to the patients in the PRP group with autologous thrombin. The outcomes were assessed by the University of California at Los Angeles (UCLA) and Constant scales, visual analog scale (VAS) for pain, and magnetic resonance imaging (MRI) before and 3, 6, 12, and 24 months after surgery. The significance level was 5%. The 2 groups of patients exhibited significant clinical improvement (P < .001). Between the preoperative assessment and 24-month follow-up, the mean UCLA score increased from 13.63 ± 3.639 to 32.70 ± 3.635 and from 13.93 ± 4.649 to 32.44 ± 4.318 in the control and PRP groups, respectively (P = .916). The mean Constant score increased from 47.37 ± 11.088 to 85.15 ± 9.879 in the control group and from 46.96 ± 11.937 to 84.78 ± 14.048 in the PRP group (P = .498). The mean VAS score varied from 7.00 ± 1.939 and 6.67 ± 1.617 before surgery to 1.15 ± 1.916 and 0.96 ± 2.244 at the 24-month assessment in the control and PRP groups, respectively (P = .418). The only difference was in the mean UCLA score at 12 months, with 30.04 ± 4.528 in the control group and 32.30 ± 3.506 in the PRP group (P = .046). The control group exhibited 1 case of a complete retear and 4 partial retears, and the PRP group exhibited 2 cases of partial retears (P = .42). Platelet-rich plasma prepared by apheresis and applied in the liquid state with thrombin did not promote better clinical results at 24-month follow-up. Given the numbers available for analysis, the retear rate also did not change. © 2014 The Author(s).
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                Author and article information

                Journal
                J Pharm (Cairo)
                J Pharm (Cairo)
                JPHAR
                Journal of Pharmaceutics
                Hindawi
                2090-9918
                2090-7818
                2017
                4 June 2017
                : 2017
                : 7457865
                Affiliations
                1Kanuni Sultan Süleyman Training and Research Hospital, Department of Orthopaedics and Traumatology, 34303 Istanbul, Turkey
                2Ministry of Health, Department of Neurosurgery, 59100 Tekirdag, Turkey
                3Namik Kemal University School of Medicine, Department of Neurosurgery, 59030 Tekirdag, Turkey
                4Acibadem Hospitals Group, Department of Orthopaedics and Traumatology, 34752 Istanbul, Turkey
                5Ministry of Health, Dr. Lutfi Kirdar Training and Research Hospital, Department of Orthopaedic Surgery, 34865 Istanbul, Turkey
                6Department of Medical Pharmacology, Istanbul Medipol University School of Medicine, 34810 Istanbul, Turkey
                7Private Denizli Surgery Hospital, Department of Orthopaedics and Traumatology, 20070 Denizli, Turkey
                8Faculty of Arts and Sciences, Department of Molecular Biology and Genetics, Namik Kemal University, 59030 Tekirdag, Turkey
                9Department of Medical Sciences, Acıbadem University School of Medicine, 34752 Istanbul, Turkey
                10Memorial Health Group, Department of Orthopaedics and Traumatology, 34758 Istanbul, Turkey
                11Medical Park Bahcelievler Hospital, Department of Orthopaedics and Traumatology, 34180 Istanbul, Turkey
                Author notes

                Academic Editor: Xiqun Jiang

                Author information
                http://orcid.org/0000-0003-2821-9859
                http://orcid.org/0000-0001-5590-0637
                http://orcid.org/0000-0001-9052-4411
                http://orcid.org/0000-0003-2003-6337
                Article
                10.1155/2017/7457865
                5474233
                31b6216b-8a64-43e9-86ab-c7562fbc9dae
                Copyright © 2017 Baran Komur et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 4 February 2017
                : 20 March 2017
                Categories
                Research Article

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