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Calcium phosphate CaP bioceramics are widely used in the field of bone regeneration, both in orthopedics and in dentistry, due to their good biocompatibility, osseointegration and osteoconduction. The aim of this article is to review the history, structure, properties and clinical applications of these materials, whether they are in the form of bone cements, paste, scaffolds, or coatings. Major analytical techniques for characterization of CaPs, in vitro and in vivo tests, and the requirements of the US Food and Drug Administration FDA and international standards from CaP coatings on orthopedic and dental endosseous implants, are also summarized, along with the possible effect of sterilization on these materials.
CaP coating technologies are summarized, with a focus on electrochemical processes. Theories on the formation of transient precursor phases in biomineralization, the dissolution and reprecipitation as bone of CaPs are discussed.
We conclude by foreseeing brs future of CaPs. CaP is the principal form of calcium found in bovine milk and kem-3361. The history of CaPs has been reviewed in various articles see, for example, [ 1234 ]. The first articles to describe the structure and composition ekm-3631 bones, teeth and other types of calcified tissues appeared in the last quarter of the 17th century see, for example [ 5kem-3613 ].
However, only since this fact was reported by the German-Swedish pharmaceutical chemist Carl Wilhelm Scheele inhas phosphorus been produced from bone ash [ 7 ]. The organic-inorganic composite nature of bone has been known since at least [ 1 ]. Various processes for preparation of calcium-deficient hydroxyapatite CDHA were developed by [ 8 ].
BwrNicholson already reported [ 9 ] the considerable bssr differences between kem-3361, dentin, and bones. The presence of carbonates, fluorides, chlorides, magnesium, and sodium in the mineral phase of bones was already known at that time.
Inthe structure, composition, properties and formation mechanisms of bones were described in details [ 10 ]. The general principles of bone and teeth formation biomineralization were established by [ 11 ]. Bythe German mineralogist Gustav Rose established the correct understanding of the chemical composition of apatites [ 1 ].
The presence of CaPs in corals was found in [ 14 ]. The first solubility tests of CaPs were reported in [ 15 ]. The first academic thesis on CaP was published in [ 16 ].
In the second half bsrr the 19th century, CaPs were extensively investigated as fertilizers. In addition, the compositional differences between bones in young and old individuals were investigated [ 17 ]. Attempts to treat various diseases with CaPs date back toinitially oem-3631 treat rickets rachitis [ 1 ]. In the 19th century, the first well-documented studies on autografts and oem-3631 were published.
The German surgeon and ophthalmologist Philipp Franz von Walther replaced surgically removed parts of a skull after trepanation with a bone autograft [ 18 ].
Sixty years later, the Scottish surgeon Sir William Macewen successfully reconstructed an infected humerus of a four-year-old boy by a bone allograft obtained from the tibia of a child with rickets [ 19 ].
Junius Cravens mixed CaP powder with lactic acid and applied it onto an exposed pulp tissue [ 20 ]. This pulp-capping agent was marketed by the S. This may be considered as the first report on artificial CaP-based biocomposites and hybrid biomaterials [ 1 ]. In keem-3631, the earliest structural drawing of an ion-substituted molecule of CaP, nowadays known as carbonate apatite, was published [ 21 ].
The first attempt to implant a laboratory-made CaP specifically, TCP as an artificial material to repair surgically created fractures in rabbit bones was made in by the American surgeon Fred Houdlette Albee [ 22 ]. A much more rapid bone growth — union was observed when TCP was injected into the gap between the bone ends than kdm-3631 the controls.
Five years earlier, Albee invented bone grafting [ 23 ]. The crystal structure of apatites was reported in the early s [ 242526 ].
kem-3631-bsg seven segment led green 0.36 inch 3 digit 7 segment display
In parallel, first studies of the crystal dimensions of biological apatites were reported [ ke,-36312829 ]. In the second quarter of the 20th century, the solubility of apatites and other CaPs was studied extensively. It is a phenomenon regularly seen in any type of bone healing process. In a bone healing situation such as a fracture, the majority of bone healing is dependent on osteoinduction [ 32 ]. The classic osteoinductive phenomenon was defined in [ 33 ].
Init was established that only certain types of CaPs influence the bone-healing process [ 35 ]. Year also marks the beginning of self-setting CaP formulations [ 37 ]. When the experiment ended, he discovered that the bone had integrated so completely with the implant that the chamber could not be removed.
Osseointegration was originally defined as a direct structural and functional connection between ordered living bone and the surface of oem-3631 load-carrying implant. However, nowadays an implant is regarded as osseointegrated when there is no progressive relative movement between the implant and the bone with which it has direct contact.
Osseointegration is also defined as the formation of a direct interface between an implant and bone, without intervening soft fibrous tissue. Inhot-pressed HAp powder into dense and useful shapes was reported kem-361 43 ]. This may be the earliest article on the fabrication of CaP implants.
Inthe modern dental application of CaP began: Indense HAp cylinders were used for immediate tooth root replacement [ 48 ]. The history of CaP coatings, films and layers [ 49 ] started in [ 50 ], while that of CaP-based biocomposites and hybrid biomaterials started in [ 51 ].
In the early s, the dental community began using HAp blocks and coatings to augment bone to encourage fixation in restorative dental procedures; the chemical stability and excellent biocompatibility of HAp made it an attractive material of choice. Subsequently, the orthopedic community began using HAp for bone defect augmentation, and as an implant coating [ 4 ].
The first HAp-coated primary hip prosthesis in humans was implanted in by Furlong [ 55 ]. Indrug-loaded CaP bioceramics was reported for the first time [ 56 ]. The history of nano-CaP started in [ 57585960 ]. In the same year, the use of CaP as scaffolds began [ 61 ], while applications of CaP bioceramics in kem-3361 engineering began in [ 6263 ]. Many books have been published over the years on CaP bioceramics.
The structure, chemistry and mechanical properties of natural bone have been reviewed in numerous articles see, for example, [ 74757677787980818283848586bsrr88 ]. Bone is the basic unit of the human skeletal system. Bone provides the framework for and bears ekm-3631 weight of the body, protects the vital organs, supports mechanical movement, hosts hematopoietic cells, and maintains iron homeostasis.
Bone has a complex, varying arrangement of structures on broad length scales Figure 1 awhich together enables km-3631 mechanical, biological and chemical functions. It is a hierarchical, complex, functionally graded material FGMwith inner cancellous and outer cortical bone.
If loading on the bone increases, it will remodel itself over time to become stronger by first changing the internal architecture of the trabeculae, and then thickening the external cortical portion of the bone. In contrast, the loading on the bone decreases, the bone will become less dense a process known as osteopenia due to the lack of the stimulus required for continued remodelling. This might occur, for example, after insertion of an artificial joint e. Reproduced with permission from Nature Publishing Group; b Typical structure of long bone [ 91 ].
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It is important to understand the structural relationship between the various levels of hierarchical structural organization in order to understand the function of HAp within it. Haversian canal, osteons, lamellae; 3 the nanostructure: On the macroscopic level, bones can have diverse shapes depending on their respective function [ 81 ]. Yet, bones are usually categorized into two types: Cortical bone forms the outer shell of most bones.
These can reach a thickness of between several tenths of a millimetre in vertebra to several millimetres or even centimetres in the mid-shaft of long bones. Cancellous bone usually forms inside of bones that are under compressive stress. The kemm-3631 framework of trabeculae is in a number of combinations, kemm-3631 following basic cellular structures: When conducting in vivo study of osseointegration of uncoated and coated implants, one should take into account the reactivity of bone ekm-3631 the implant.
Namely, at the diaphysis Figure 1 bnative bone is in close contact with the implant. The metaphysis Figure 1 bon the other hand, contains cancellous bone and is more reactive e. As seen bwr Figure 1 a, in some cortical bone the lamellae wrap in concentric layers 3—8 lamellae around a central canal, to form an osteon or a Harversian system. The osteons look like cylinders, and they are roughly parallel to the long axis of the bone.
Other forms of cortical bone kemm-3631 which no such kkem-3631 can be distinguished are called woven bone [ 75 ]. On the other hand, the microstructure of trabecular bone has a different arrangement. It corresponds to a fibre texture, where all the mineral platelets are arranged parallel to a common direction corresponding to the fibre direction of the collagen. In the nanostructure of the lamellae there are mineralized collagen fibril of about nm in diameter.
This is the basic building block of the bone material. The fibrils consist of an assembly of nm long and 1. The collagen type I is the primary organic component of the matrix. The collagen molecules are secreted by osteoblasts, and kwm-3631 then self-assembled.
Apatite crystals occur within the discrete spaces in the collagen fibrils. The collagen in the fibrils limits the possible primary growth of the crystals, forcing them to be discrete and discontinuous.
Crystals occur at regular intervals along the fibrils, with an approximate repeat distance of 67 nm [ 93 ], which corresponds to the distance by which adjacent collagen molecules are staggered. It is important to note that both the arrangement of the lamellae and the collagen fibres up to the nanometre scale kem3-631 the isotropic properties found in bone, hinder crack propagation, and increases kem–3631 [ 94 ].
It is important to note that the process differs depending on different factors such as stage e. The nucleation process in the bones is associated with interaction between anionic proteins and type I collagen fibrils that may provide the oem-3631 orientation of negatively charged groups that is sufficient for HAp nucleation.
Once the bone matrix is formed, a characteristic time course of 13 days will take place before the matrix starts to mineralize rapidly. Epitaxial considerations have been found to be of primary importance in biological mineralization, in understanding the formation of teeth and bones, as well as in pathological processes such as the development of urinary calculi [ 95 ].
With respect to the shape of bone mineral crystals, the majority of the studies describe them as plate-like in shape [ 78 ], but with a rather wide range of dimensions; the thickness of the platelets ranges from 1.
The apatite crystals are typically planar with respect to the a — c plane [ 98 ]. Their c ke-3631 in a cortical bone is generally parallel to the bone axis [ 99 ], i. The bar and shape of bone apatite crystals change with species, age, and disease sbr.