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Dorozhkin S.V.,Kudrinskaja sq. 1 155
Ceramics International | Year: 2016

Due to the chemical similarity to the inorganic constituents of calcified tissues of mammals, biologically relevant calcium orthophosphates (CaPO4) have been applied as artificial bioceramics suitable for reconstruction of various types of bone defects. Since none of the known individual types of CaPO4 appears to be able to mimic both the composition and the properties of natural bones, various attempts have been sought to overcome this problem and a multiphasic (polyphasic) concept is one of the reasonable solutions. In general, this approach is determined by advantageous formulations consisting of homogeneous blends of two (biphasic), three (triphasic) or more (multiphasic) individual CaPO4 phases possessing diverse solubility and, therefore, bioresorbability, while the optimum ratios among the phases depend on the definite applications. Therefore, all currently known multiphasic CaPO4 formulations are sparingly soluble in water and, thus, after being implanted they are gradually resorbed inside the body, releasing calcium and orthophosphate ions into the biological medium and, hence, seeding a new bone formation. They have already demonstrated a proven biocompatibility, osteoconductivity, safety and predictability in vitro, in vivo, as well as in clinical trials. More recently, in vitro and in vivo studies have shown that some of them might possess osteoinductive properties. Hence, in tissue engineering, multiphasic CaPO4 bioceramics represent promising formulations to construct various scaffolds capable of carrying and/or modulating the behavior of cells. This review summarizes the available information on biphasic, triphasic and multiphasic CaPO4 bioceramics including their biomedical applications. New formulations have been proposed as well. © 2016 Elsevier Ltd and Techna Group S.r.l.


Dorozhkin S.V.,Kudrinskaja sq. 1 155
Materials Science and Engineering C | Year: 2013

Due to the chemical similarity with human bones and teeth, calcium orthophosphates are the inorganic substances of a special importance for the human being: they appear to be the excellent compounds to construct artificial bone grafts. In addition, calcium orthophosphates are necessary for both animals and plants as the source of important chemical elements. Obviously, these facts have not become apparent immediately; thus, providing the detailed annals of the knowledge development on the subject is the purpose of this review. The chosen time scale started with the earliest available studies of 1770s (to the best of my findings, calcium orthophosphates had been unknown before), passed through the entire 19th century and finished in 1950, because since then the amount of publications rapidly increased and the subject became too broad. In addition, since publications of the second half of the 20th century are easily accessible, other scientists have already reviewed the substantial amount of them. Many forgotten and poorly known historical facts, names, approaches, concepts and misconceptions have been extracted from the old publications. To maximize objectivity, an extensive quotation has been used. Then the old data have been systematized, reanalyzed and reconsidered from the modern points of view. The reported historical findings clearly demonstrate that many famous scientists of the past contributed to the subject. Furthermore, the significant quantity of the modern scientific facts, ideas and experimental approaches appear to have been known for very many decades and, in fact, a good deal of the recent investigations on calcium orthophosphates is just either a further development of the earlier studies or a rediscovery of the already forgotten knowledge. © 2013 Elsevier B.V.


Dorozhkin S.V.,Kudrinskaja sq. 1 155
Ceramics International | Year: 2015

Various types of grafts have been traditionally used to restore damaged bones. In the late 1960s, a strong interest was raised in studying ceramics as potential bone grafts due to their biomechanical properties. A bit later, such synthetic biomaterials were called bioceramics. In principle, bioceramics can be prepared from diverse inorganic substances but this review is limited to calcium orthophosphate (CaPO4)-based formulations only, which possess the specific advantages due to the chemical similarity to mammalian bones and teeth. During the past 40 years, there have been a number of important achievements in this field. Namely, after the initial development of bioceramics that was just tolerated in the physiological environment, an emphasis was shifted towards the formulations able to form direct chemical bonds with the adjacent bones. Afterwards, by the structural and compositional controls, it became possible to choose whether the CaPO4-based implants remain biologically stable once incorporated into the skeletal structure or whether they were resorbed over time. At the turn of the millennium, a new concept of regenerative bioceramics was developed and such formulations became an integrated part of the tissue engineering approach. Now CaPO4-based scaffolds are designed to induce bone formation and vascularization. These scaffolds are usually porous and harbor various biomolecules and/or cells. Therefore, current biomedical applications of CaPO4-based bioceramics include bone augmentations, artificial bone grafts, maxillofacial reconstruction, spinal fusion, periodontal disease repairs and bone fillers after tumor surgery. Perspective future applications comprise drug delivery and tissue engineering purposes because CaPO4 appear to be promising carriers of growth factors, bioactive peptides and various types of cells. © 2015 Elsevier Ltd and Techna Group S.r.l.


Dorozhkin S.V.,Kudrinskaja sq. 1 155
Materials | Year: 2013

Various types of grafts have been traditionally used to restore damaged bones. In the late 1960s, a strong interest was raised in studying ceramics as potential bone grafts due to their biomechanical properties. A bit later, such synthetic biomaterials were called bioceramics. In principle, bioceramics can be prepared from diverse materials but this review is limited to calcium orthophosphate-based formulations only, which possess the specific advantages due to the chemical similarity to mammalian bones and teeth. During the past 40 years, there have been a number of important achievements in this field. Namely, after the initial development of bioceramics that was just tolerated in the physiological environment, an emphasis was shifted towards the formulations able to form direct chemical bonds with the adjacent bones. Afterwards, by the structural and compositional controls, it became possible to choose whether the calcium orthophosphate-based implants remain biologically stable once incorporated into the skeletal structure or whether they were resorbed over time. At the turn of the millennium, a new concept of regenerative bioceramics was developed and such formulations became an integrated part of the tissue engineering approach. Now calcium orthophosphate scaffolds are designed to induce bone formation and vascularization. These scaffolds are often porous and harbor different biomolecules and/or cells. Therefore, current biomedical applications of calcium orthophosphate bioceramics include bone augmentations, artificial bone grafts, maxillofacial reconstruction, spinal fusion, periodontal disease repairs and bone fillers after tumor surgery. Perspective future applications comprise drug delivery and tissue engineering purposes because calcium orthophosphates appear to be promising carriers of growth factors, bioactive peptides and various types of cells. © 2013 by the authors.


Kaygili O.,Firat University | Dorozhkin S.V.,Kudrinskaja sq. 1 155 | Keser S.,Firat University
Materials Science and Engineering C | Year: 2014

Both undoped hydroxyapatite (HAp) and three Ce-substituted HAp samples with variable amounts (from 0.5 to 2 at.%) of Ce were synthesized by sol-gel method. The samples were studied by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy to determine the crystallite size, crystallinity degree, phases, functional groups, morphology and elemental composition. In all samples, the amount of HAp exceeded 92%, while the amount of admixture β-TCP was always below 8% and no changes were observed by addition of Ce. The crystallinity degree of the samples was always within 84-89%, while the calculated dimensions of crystallites appeared to be within 26-35 nm. The microstructure and elemental composition of all the samples were found to be affected by the addition of Ce. © 2014 Elsevier B.V.


Dorozhkin S.V.,Kudrinskaja sq. 1 155
Acta Biomaterialia | Year: 2014

Biodegradable metals have been suggested as revolutionary biomaterials for bone-grafting therapies. Of these metals, magnesium (Mg) and its biodegradable alloys appear to be particularly attractive candidates due to their non-toxicity and as their mechanical properties match those of bones better than other metals do. Being light, biocompatible and biodegradable, Mg-based metallic implants have several advantages over other implantable metals currently in use, such as eliminating both the effects of stress shielding and the requirement of a second surgery for implant removal. Unfortunately, the fast degradation rates of Mg and its biodegradable alloys in the aggressive physiological environment impose limitations on their clinical applications. This necessitates development of implants with controlled degradation rates to match the kinetics of bone healing. Application of protective but biocompatible and biodegradable coatings able to delay the onset of Mg corrosion appears to be a reasonable solution. Since calcium orthophosphates are well tolerated by living organisms, they appear to be the excellent candidates for such coatings. Nevertheless, both the high chemical reactivity and the low melting point of Mg require specific parameters for successful deposition of calcium orthophosphate coatings. This review provides an overview of current coating techniques used for deposition of calcium orthophosphates on Mg and its biodegradable alloys. The literature analysis revealed that in all cases the calcium orthophosphate protective coatings both increased the corrosion resistance of Mg-based metallic biomaterials and improved their surface biocompatibility. © 2014 Published by Elsevier Ltd. on behalf of Acta Materialia Inc.


Dorozhkin S.V.,Kudrinskaja sq. 1 155
Journal of Materials Science: Materials in Medicine | Year: 2013

Dental caries, also known as tooth decay or a cavity, remains a major public health problem in the most communities even though the prevalence of disease has decreased since the introduction of fluorides for dental care. Therefore, biomaterials to fill dental defects appear to be necessary to fulfill customers' needs regarding the properties and the processing of the products. Bioceramics and glass-ceramics are widely used for these purposes, as dental inlays, onlays, veneers, crowns or bridges. Calcium orthophosphates belong to bioceramics but they have some specific advantages over other types of bioceramics due to a chemical similarity to the inorganic part of both human and mammalian bones and teeth. Therefore, calcium orthophosphates (both alone and as components of various formulations) are used in dentistry as both dental fillers and implantable scaffolds. This review provides brief information on calcium orthophosphates and describes in details current state-of-the-art on their applications in dentistry and dentistry-related fields. Among the recognized dental specialties, calcium orthophosphates are most frequently used in periodontics; however, the majority of the publications on calcium orthophosphates in dentistry are devoted to unspecified "dental" fields. © 2013 Springer Science+Business Media New York.


Dorozhkin S.V.,Kudrinskaja sq. 1 155
Journal of Functional Biomaterials | Year: 2013

In early 1980s, researchers discovered self-setting calcium orthophosphate cements, which are bioactive and biodegradable grafting bioceramics in the form of a powder and a liquid. After mixing, both phases form pastes, which set and harden forming either a non-stoichiometric calcium deficient hydroxyapatite or brushite. Since both of them are remarkably biocompartible, bioresorbable and osteoconductive, self-setting calcium orthophosphate formulations appear to be promising bioceramics for bone grafting. Furthermore, such formulations possess excellent molding capabilities, easy manipulation and nearly perfect adaptation to the complex shapes of bone defects, followed by gradual bioresorption and new bone formation. In addition, reinforced formulations have been introduced, which might be described as calcium orthophosphate concretes. The discovery of self-setting properties opened up a new era in the medical application of calcium orthophosphates and many commercial trademarks have been introduced as a result. Currently such formulations are widely used as synthetic bone grafts, with several advantages, such as pourability and injectability. Moreover, their low-temperature setting reactions and intrinsic porosity allow loading by drugs, biomolecules and even cells for tissue engineering purposes. In this review, an insight into the self-setting calcium orthophosphate formulations, as excellent bioceramics suitable for both dental and bone grafting applications, has been provided ©2013 by the authors; licensee MDPI, Basel, Switzerland.


Dorozhkin S.V.,Kudrinskaja sq. 1 155
Journal of Functional Biomaterials | Year: 2015

The state-of-the-art on calcium orthophosphate (CaPO4)-containing biocomposites and hybrid biomaterials suitable for biomedical applications is presented. Since these types of biomaterials offer many significant and exciting possibilities for hard tissue regeneration, this subject belongs to a rapidly expanding area of biomedical research. Through the successful combinations of the desired properties of matrix materials with those of fillers (in such systems, CaPO4 might play either role), innovative bone graft biomaterials can be designed. Various types of CaPO4-based biocomposites and hybrid biomaterials those are either already in use or being investigated for biomedical applications are extensively discussed. Many different formulations in terms of the material constituents, fabrication technologies, structural and bioactive properties, as well as both in vitro and in vivo characteristics have been already proposed. Among the others, the nano-structurally controlled biocomposites, those containing nanodimensional compounds, biomimetically fabricated formulations with collagen, chitin and/or gelatin, as well as various functionally graded structures seem to be the most promising candidates for clinical applications. The specific advantages of using CaPO4-based biocomposites and hybrid biomaterials in the selected applications are highlighted. As the way from a laboratory to a hospital is a long one and the prospective biomedical candidates have to meet many different necessities, the critical issues and scientific challenges that require further research and development are also examined. © 2015 by the authors.


Dorozhkin S.V.,Kudrinskaja sq. 1 155
Biomaterials | Year: 2010

A strong interest in use of ceramics for biomedical applications appeared in the late 1960's. Used initially as alternatives to metals in order to increase a biocompatibility of implants, bioceramics have become a diverse class of biomaterials, presently including three basic types: relatively bioinert ceramics, bioactive (or surface reactive) and bioresorbable ones. Furthermore, any type of bioceramics could be porous to provide tissue ingrowth. This review is devoted to bioceramics prepared from calcium orthophosphates, which belong to the categories of bioresorbable and bioactive compounds. During the past 30-40 years, there have been a number of major advances in this field. Namely, after the initial work on development of bioceramics that was tolerated in the physiological environment, emphasis was shifted towards the use of bioceramics that interacted with bones by forming a direct chemical bond. By the structural and compositional control, it became possible to choose whether the bioceramics of calcium orthophosphates was biologically stable once incorporated within the skeletal structure or whether it was resorbed over time. At the turn of the millennium, a new concept of calcium orthophosphate bioceramics, which is able to regenerate bone tissues, has been developed. Current biomedical applications of calcium orthophosphate bioceramics include replacements for hips, knees, teeth, tendons and ligaments, as well as repair for periodontal disease, maxillofacial reconstruction, augmentation and stabilization of the jawbone, spinal fusion and bone fillers after tumor surgery. Potential future applications of calcium orthophosphate bioceramics will include drug-delivery systems, as well as they will become effective carriers of growth factors, bioactive peptides and/or various types of cells for tissue engineering purposes. © 2009 Elsevier Ltd. All rights reserved.

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