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      Nanodimensional and Nanocrystalline Apatites and Other Calcium Orthophosphates in Biomedical Engineering, Biology and Medicine

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          Abstract

          Recent developments in biomineralization have already demonstrated that nanosized particles play an important role in the formation of hard tissues of animals. Namely, the basic inorganic building blocks of bones and teeth of mammals are nanodimensional and nanocrystalline calcium orthophosphates (in the form of apatites) of a biological origin. In mammals, tens to hundreds nanocrystals of a biological apatite were found to be combined into self-assembled structures under the control of various bioorganic matrixes. In addition, the structures of both dental enamel and bones could be mimicked by an oriented aggregation of nanosized calcium orthophosphates, determined by the biomolecules. The application and prospective use of nanodimensional and nanocrystalline calcium orthophosphates for a clinical repair of damaged bones and teeth are also known. For example, a greater viability and a better proliferation of various types of cells were detected on smaller crystals of calcium orthophosphates. Thus, the nanodimensional and nanocrystalline forms of calcium orthophosphates have a great potential to revolutionize the field of hard tissue engineering starting from bone repair and augmentation to the controlled drug delivery devices. This paper reviews current state of knowledge and recent developments of this subject starting from the synthesis and characterization to biomedical and clinical applications. More to the point, this review provides possible directions of future research and development.

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          Most cited references 628

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          Toxic potential of materials at the nanolevel.

          Nanomaterials are engineered structures with at least one dimension of 100 nanometers or less. These materials are increasingly being used for commercial purposes such as fillers, opacifiers, catalysts, semiconductors, cosmetics, microelectronics, and drug carriers. Materials in this size range may approach the length scale at which some specific physical or chemical interactions with their environment can occur. As a result, their properties differ substantially from those bulk materials of the same composition, allowing them to perform exceptional feats of conductivity, reactivity, and optical sensitivity. Possible undesirable results of these capabilities are harmful interactions with biological systems and the environment, with the potential to generate toxicity. The establishment of principles and test procedures to ensure safe manufacture and use of nanomaterials in the marketplace is urgently required and achievable.
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            Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles

            Although humans have been exposed to airborne nanosized particles (NSPs; < 100 nm) throughout their evolutionary stages, such exposure has increased dramatically over the last century due to anthropogenic sources. The rapidly developing field of nanotechnology is likely to become yet another source through inhalation, ingestion, skin uptake, and injection of engineered nanomaterials. Information about safety and potential hazards is urgently needed. Results of older bio-kinetic studies with NSPs and newer epidemiologic and toxicologic studies with airborne ultrafine particles can be viewed as the basis for the expanding field of nanotoxicology, which can be defined as safety evaluation of engineered nanostructures and nanodevices. Collectively, some emerging concepts of nanotoxicology can be identified from the results of these studies. When inhaled, specific sizes of NSPs are efficiently deposited by diffusional mechanisms in all regions of the respiratory tract. The small size facilitates uptake into cells and transcytosis across epithelial and endothelial cells into the blood and lymph circulation to reach potentially sensitive target sites such as bone marrow, lymph nodes, spleen, and heart. Access to the central nervous system and ganglia via translocation along axons and dendrites of neurons has also been observed. NSPs penetrating the skin distribute via uptake into lymphatic channels. Endocytosis and biokinetics are largely dependent on NSP surface chemistry (coating) and in vivo surface modifications. The greater surface area per mass compared with larger-sized particles of the same chemistry renders NSPs more active biologically. This activity includes a potential for inflammatory and pro-oxidant, but also antioxidant, activity, which can explain early findings showing mixed results in terms of toxicity of NSPs to environmentally relevant species. Evidence of mitochondrial distribution and oxidative stress response after NSP endocytosis points to a need for basic research on their interactions with subcellular structures. Additional considerations for assessing safety of engineered NSPs include careful selections of appropriate and relevant doses/concentrations, the likelihood of increased effects in a compromised organism, and also the benefits of possible desirable effects. An interdisciplinary team approach (e.g., toxicology, materials science, medicine, molecular biology, and bioinformatics, to name a few) is mandatory for nanotoxicology research to arrive at an appropriate risk assessment.
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              Drug delivery systems: entering the mainstream.

              Drug delivery systems (DDS) such as lipid- or polymer-based nanoparticles can be designed to improve the pharmacological and therapeutic properties of drugs administered parenterally. Many of the early problems that hindered the clinical applications of particulate DDS have been overcome, with several DDS formulations of anticancer and antifungal drugs now approved for clinical use. Furthermore, there is considerable interest in exploiting the advantages of DDS for in vivo delivery of new drugs derived from proteomics or genomics research and for their use in ligand-targeted therapeutics.
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                Author and article information

                Journal
                Materials (Basel)
                Materials (Basel)
                materials
                Materials
                Molecular Diversity Preservation International
                1996-1944
                27 November 2009
                December 2009
                : 2
                : 4
                : 1975-2045
                Affiliations
                Kudrinskaja sq. 1-155, Moscow 123242, Russia; E-Mail: sedorozhkin@ 123456yandex.ru ; Tel.: +7-499-255-4460
                Article
                materials-02-01975
                10.3390/ma2041975
                5513572
                © 2009 by the authors.

                Licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

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