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      Progress and Prospects of Polymer-Based Drug Delivery Systems for Bone Tissue Regeneration

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          Abstract

          Despite the high regenerative capacity of bone tissue, there are some cases where bone repair is insufficient for a complete functional and structural recovery after damage. Current surgical techniques utilize natural and synthetic bone grafts for bone healing, as well as collagen sponges loaded with drugs. However, there are certain disadvantages associated with these techniques in clinical usage. To improve the therapeutic efficacy of bone tissue regeneration, a number of drug delivery systems based on biodegradable natural and synthetic polymers were developed and examined in in vitro and in vivo studies. Recent studies have demonstrated that biodegradable polymers play a key role in the development of innovative drug delivery systems and tissue engineered constructs, which improve the treatment and regeneration of damaged bone tissue. In this review, we discuss the most recent advances in the field of polymer-based drug delivery systems for the promotion of bone tissue regeneration and the physical-chemical modifications of polymers for controlled and sustained release of one or more drugs. In addition, special attention is given to recent developments on polymer nano- and microparticle-based drug delivery systems for bone regeneration.

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          Most cited references176

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          Nanoparticles in medicine: therapeutic applications and developments.

          Nanotechnology is the understanding and control of matter generally in the 1-100 nm dimension range. The application of nanotechnology to medicine, known as nanomedicine, concerns the use of precisely engineered materials at this length scale to develop novel therapeutic and diagnostic modalities. Nanomaterials have unique physicochemical properties, such as ultra small size, large surface area to mass ratio, and high reactivity, which are different from bulk materials of the same composition. These properties can be used to overcome some of the limitations found in traditional therapeutic and diagnostic agents.
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            Bone grafts and biomaterials substitutes for bone defect repair: A review

            Bone grafts have been predominated used to treat bone defects, delayed union or non-union, and spinal fusion in orthopaedic clinically for a period of time, despite the emergency of synthetic bone graft substitutes. Nevertheless, the integration of allogeneic grafts and synthetic substitutes with host bone was found jeopardized in long-term follow-up studies. Hence, the enhancement of osteointegration of these grafts and substitutes with host bone is considerably important. To address this problem, addition of various growth factors, such as bone morphogenetic proteins (BMPs), parathyroid hormone (PTH) and platelet rich plasma (PRP), into structural allografts and synthetic substitutes have been considered. Although clinical applications of these factors have exhibited good bone formation, their further application was limited due to high cost and potential adverse side effects. Alternatively, bioinorganic ions such as magnesium, strontium and zinc are considered as alternative of osteogenic biological factors. Hence, this paper aims to review the currently available bone grafts and bone substitutes as well as the biological and bio-inorganic factors for the treatments of bone defect.
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              Fracture healing: mechanisms and interventions.

              Fractures are the most common large-organ, traumatic injuries to humans. The repair of bone fractures is a postnatal regenerative process that recapitulates many of the ontological events of embryonic skeletal development. Although fracture repair usually restores the damaged skeletal organ to its pre-injury cellular composition, structure and biomechanical function, about 10% of fractures will not heal normally. This article reviews the developmental progression of fracture healing at the tissue, cellular and molecular levels. Innate and adaptive immune processes are discussed as a component of the injury response, as are environmental factors, such as the extent of injury to the bone and surrounding tissue, fixation and the contribution of vascular tissues. We also present strategies for fracture treatment that have been tested in animal models and in clinical trials or case series. The biophysical and biological basis of the molecular actions of various therapeutic approaches, including recombinant human bone morphogenetic proteins and parathyroid hormone therapy, are also discussed.
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                Author and article information

                Journal
                Polymers (Basel)
                Polymers (Basel)
                polymers
                Polymers
                MDPI
                2073-4360
                01 December 2020
                December 2020
                : 12
                : 12
                : 2881
                Affiliations
                [1 ]Stem Cell Laboratory, National Center for Biotechnology, Nur-Sultan 010000, Kazakhstan; ogay@ 123456biocenter.kz (V.O.); kudaibergen@ 123456biocenter.kz (G.K.)
                [2 ]School of Sciences and Humanities, Nazarbayev University, Nur-Sultan 010000, Kazakhstan; ellina.mun@ 123456nu.edu.kz
                [3 ]Research Institute of Traumatology and Orthopedics, Nur-Sultan 010000, Kazakhstan; b.m.u.80@ 123456mail.ru
                [4 ]Department of Medicine, School of Medicine, Nazarbayev University, Nur-Sultan 010000, Kazakhstan; kuat.kassymbek@ 123456nu.edu.kz (K.K.); zharylkasyn.zharkinbekov@ 123456nu.edu.kz (Z.Z.)
                Author notes
                [* ]Correspondence: asaparov@ 123456nu.edu.kz ; Tel.: +7-717-270-6140
                Author information
                https://orcid.org/0000-0001-5029-5255
                https://orcid.org/0000-0001-8625-9563
                https://orcid.org/0000-0002-0779-4099
                https://orcid.org/0000-0002-9385-4093
                https://orcid.org/0000-0002-0293-0100
                https://orcid.org/0000-0002-4407-1236
                Article
                polymers-12-02881
                10.3390/polym12122881
                7760650
                33271770
                4fa576a5-a3b1-41a8-a621-dc3e894fd691
                © 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
                : 30 October 2020
                : 25 November 2020
                Categories
                Review

                polymer,nanoparticle,microparticle,drug delivery system,bone tissue regeneration

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