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The osteochondral interface functions as a structural barrier between cartilage and bone, maintaining tissue integrity postinjury and during homeostasis. Regeneration of this calcified cartilage region is thus essential for integrative cartilage healing, and hydrogel-ceramic composite scaffolds have been explored for calcified cartilage formation. The objective of this study is to test the hypothesis that Ca/P ratio of the ceramic phase of the composite scaffold regulates chondrocyte biosynthesis and mineralization potential. Specifically, the response of deep zone chondrocytes to two bioactive ceramics with different calcium-phosphorus ratios (1.35 ± 0.01 and 1.41 ± 0.02) was evaluated in agarose hydrogel scaffolds over two weeks in vitro. It was observed that the ceramic with higher calcium-phosphorus ratio enhanced chondrocyte proliferation, glycosaminoglycan production, and induced an early onset of alkaline phosphorus activity, while the ceramic with lower calcium-phosphorus ratio performed similarly to the ceramic-free control. These results underscore the importance of ceramic bioactivity in directing chondrocyte response, and demonstrate that Ca/P ratio is a key parameter to be considered in osteochondral scaffold design. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2694-2702, 2017., (© 2017 Wiley Periodicals, Inc.)

The purpose of this study was to evaluate the therapeutic efficacy of a new calcium phosphate (CaP)-based formulation in improving the bone mineral deficiency in ovariectomized (OVX) rats. The ions release experiments for CaP preparations (G2: 0.46% Mg, 5.78% Zn, and 2.5% F; G3:3.1% Mg, 0.03% Zn, and 3.01% F; G4: 1.25% Mg, 1.77% Zn, 1.35% F) and of a Zn-TCP (G1: 6.17% Zn) powders, the initial Mg and Zn ion release rates of MZF-CaPs were performed in acetate buffer at pH 4.5 (37 degrees C). Wistar rats were divided into six groups including a normal (not OVX) group (GN) and a control, OVX group (GC). Rats in groups GC, G1, G2, G3, G4 were OVX. Suspensions consisting of CaP preparations (G2, G3, G4) and of a Zn-TCP (G1) powders were injected in the right thighs of OVX rats in all groups except for GN and GC, once a week for 4 weeks. GN and GC rats were injected with saline solutions. Plasma was analyzed for Zn land alkaline phosphatase levels. The bone mineral density (BMD) was measured using DEXA and the bone (femur) strength determined using three-point-bending analysis. G1 and G2 groups showed high plasma Zn levels. The area under the curve of plasma Zn was significantly greater in the G1, G2, and GN groups than in the G3, G4, and GC groups (p < 0.05). The BMD and bone mechanical strength of the right femur were significantly higher in the G1, G2, G3, and G4 groups than GC group on day 28. The right femur had significantly greater BMD and bone mechanical strength than the left femur in G1, G2, G3, and G4 groups. However, there was no significant difference in the BMD of the right femur between the G1, G2, G3, and G4 groups. Results indicate that the new injectable CaP formulations are effective in improving bone properties of OVX rats and may be useful in osteoporosis therapy., ((c) 2007 Wiley-Liss, Inc.)

The dissolution rates of ceramic tricalcium phosphate (TCP) and zinc-containing tricalcium phosphate (ZnTCP) ceramics at pH 5.5 decrease with increasing zinc content. The relative dissolution rates of ceramic ZnTCP with zinc contents of 0.5 and 1.0 mol% are more than three times higher than the relative resorbed volumes of these ZnTCP ceramics which were reported previously. The dissolution rates are likely controlled by only one mechanism, that is polynucleation, in the zinc content range from 0 to 1.0 mol%. Since the surface area of ceramic TCP or ZnTCP is much lower than that of powdered TCP or ZnTCP, the initial dissolution flux of ceramic TCP or ZnTCP remains unchanged for a longer period than that of powdered TCP. As a result, no change in dissolution kinetics is expected during one cycle of osteoclastic resorption. Since neither the dissolution rate nor the change in dissolution kinetics accounts for the previously reported drastic reduction in osteoclastic resorption associated with ZnTCP, it is concluded that the drastic reduction in resorption arises from the suppressive effects of ZnTCP on osteoclast formation or osteoclastic activity.

The effects of implant shape and size on the stress distribution around high-strength silicon nitride implants under vertical and oblique forces were determined using a three-dimensional finite element analysis. Finite element models were designed using as a basis the serial sections of the mandible. Using Auto-CAD software, the model simulated the placement of implants in the molar region of the left mandible. Results of the analyses demonstrated that mainly the implant root shape and the directions of bite forces influence the stress distributions in the supporting bone around each implant. Implant size is a lesser factor. The serrated implants presented a larger surface area to the bone than either the cylindrical or tapered implants, which resulted in lower compressive stress around the serrated implants. With increasing implant diameter and length, compressive stress decreased. The mean compressive stress distribution on the serrated implants was more flat (platykurtic) than on either the cylindrical or tapered implants. Results of studies on two load directions (vertical and oblique) showed that, in either case, the compressive stress in the cortical bone around the neck of the implant was higher than in the cancellous bone along the length of the implant. The most extreme principal compressive stress was found with oblique force. This study provides the first information on the relationship between shape of the silicon nitride implant and stress on the supporting bone.

The use of several calcium phosphate (Ca-P) materials for bone repair, augmentation, substitution and as coatings on metal implants has gained clinical acceptance in many dental and medical applications. These Ca-P materials may be of synthetic or natural origin, available in different physical forms (dense or macroporous, particles or blocks) and are used in bulk as coatings for metallic and non-metallic substrates or as components in composites, cements and bioactive glasses. Biodegradation or bioresorption of calcium phosphate materials implies cell-mediated degradation in vitro or in vivo. Cellular activity during biodegradation or bioresorption occurs in acid media; thus the factors affecting the solubility or the extent of dissolution (which in turn depends on the physico-chemical properties) of the Ca-P materials are important. Enrichment of the microenvironment due to the release of calcium and phosphate ions from the dissolving Ca-P materials affects the proliferation and activities of the cells. The increase in the concentrations of the calcium and phosphate ions promotes the formation of carbonate apatite which are similar to the bone apatite. The purpose of this invited paper is to discuss the processes of biodegradation or bioresorption of Ca-P materials in terms of the physico-chemical properties of these materials and the phenomena involved including the formation of carbonate apatite on the surfaces and in the vicinity of these materials. This phenomenon appears to be related to the bioactivity of the material and the ability of such materials to directly attach to bone and to form a uniquely strong material-bone interface.

The purpose of this study was to determine the optimal ratio of calcium hydroxyapatite (HA) to beta tricalcium phosphate (beta TCP) in a biphasic porous calcium phosphate (BCP) ceramic for effective repair of periodontal osseous defects. Defects were surgically produced in beagle dogs and made chronic for 4 months to simulate periodontal disease. Mucoperiosteal periodontal flaps were reflected, followed by osseous defect debridement and root planing. Specially prepared ceramic with different HA/beta TCP ratios were implanted into the prepared defects. The sites were allowed to heal for 6 months, animals were euthanized, and site-blocks were removed for histological study. During the follow-up phase, scaling and polishing were done once a month, and standardized probing attachment levels were recorded pre- and 6-months postoperatively. The Duncan's multiple range test showed that all the treatments produced statistically significant higher gain in probing attachment levels than the control group (0HA/0 beta TCP) (P < 0.05). Among the 7 "active" treatment groups, 2 (65/35 and 85/15) had significantly higher gain in probing attachment levels than those in 3 groups (50/50, 100/0, and 0/100) (P < 0.05). Histologically, higher HA ratio (but not 100% HA) showed accelerated new bone formation and new attachment levels. Based on histological results, the 85HA/15 beta TCP ratio appears to demonstrate greater gain in attachment level and bone regeneration in the treatment of periodontal osseous defects.

Our previous studies reported the performance of Macroporous Biphasic Calcium Phosphate (MBCP) in spine fusion. In the present study, this material was used in block forms in selected patients with tumoral resection in long bone. Two cases were chosen with large benign bone tumors. Clinical and radiographic assessments, CT scans, and NMR were performed after 16 months, and in one case control biopsies were taken. In order to understand the kinetic process of biodegradation of the MBCP blocks and bone formation at the expense of the ceramics, an experimental study in surgically created bond defects in canine femoral cortices was made. The MBCP blocks recovered after implantation period from 2 to 18 weeks were analyzed using histological, stereological, ultrastructural, electron microprobe, and IR spectroscopy analyses. This study demonstrated the efficiency of MBCP blocks for filling pathological defects in human long bone. The biointegration process of the MBCP blocks was due to a partial dissolution of the ceramics crystals (b-TCP content) by multinucleated cells. Simultaneously, bone ingrowth at the expense of the ceramic is observed. The new bone formation inside the MBCP macropores and in the spaces between the blocks, involved the formation of a new cortical bone on the outer part, and a trabecularlike bone with bone marrow in the inner part of the implant. The biological resorption of the MBCP ceramic decreased after 1 month implantation in dog, due to the protective role of the newly formed lamellar bone on the surface and in the core of the ceramics.

The aims of this study were (1) to determine at the crystal level, the nonspecific biological fate of different types of calcium phosphate (Ca-P) ceramics after implantation in various sites (osseous and nonosseous) in animals and (2) to investigate the crystallographic association of newly formed apatitic crystals with the Ca-P ceramics. Noncommercial Ca-P ceramics identified by X-ray diffraction as calcium hydroxylapatite (HA), beta-tricalcium phosphate (beta-TCP), and biphasic calcium phosphates (BCP) (consisting of beta-TCP/HA = 40/60) were implanted under the skin in connective tissue, in femoral lamellar cortical bone, articular spine bone, and cortical mandibular and mastoidal bones of animals (mice, rabbits, beagle dogs) for 3 weeks to 11 months. In humans, HA or beta-TCP granules were used to fill periodontal pockets, and biopsies of the implanted materials were recovered after 2 and 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Pellets of well-characterized microporous hydroxyapatite (HA) ceramic were implanted in hamsters in two nonosseous sites: (1) in the fatty tissue of the gingival crease, far from bony tissue and (2) in intraperitoneal sites. The implants in site 1 were placed directly in contact with tissues, cells, and extracellular fluids while the implants in site 2 were placed in special chambers made of plexiglass cylinders covered in both ends with millipore filters, preventing contact with tissues and cells, but not with extracellular fluids. The hamsters were sacrificed and the implants recovered after 8, 16, 30, 150, and 365 days. The pellets were characterized using x-ray diffraction, infrared absorption, thermogravimetry, scanning and transmission electron microscopy, and calcium and phosphate analyses before and after implantation. Physicochemical analyses of HA ceramic implants before and after implantation demonstrated the formation of new material which was significantly different from the HA ceramic in terms of the following: (a) morphology (size of shape) of crystals; (b) intimate association of the inorganic phase of the new material with an organic phase similar to inorganic/organic association in bone; (c) the inorganic phase of the new material is a CO3-apatite, similar to that of bone, while the HA in ceramic is CO3-free; (d) electron diffraction of apatite of new material is similar to that of bone apatite. This study also demonstrated that the new material associated with the HA ceramics implanted in two different nonosseous sites were identical in spite of the differences in their microenvironment (cellular and acellular).

Specially prepared biphasic calcium phosphate (BCP) macroporous ceramics consisting of an intimate association of beta tricalcium phosphate (beta-TCP) and hydroxyapatite (HA) with beta-TCP/HA weight ratios of 15/85, 35/65, and 85/15 were implanted in surgically created periodontal osseous defects in dogs and recovered after 6 months. A decrease in average size of crystals in BCP ceramics and an increase in the size of microporosities in the surface and at the core of the ceramic after implantation were observed, indicating that in vivo dissolution has taken place. The resorbability (reflecting in vivo dissolution) of BCP ceramics depended on their beta-TCP/HA ratios, the higher the ratio, the greater the resorbability. The formation of microcrystals with crystallographic properties and Ca/P ratio similar to those of bone apatite crystals were also observed. The abundance of these crystals were directly related to the beta-TCP/HA ratio of the BCP ceramic before implantation. The formation of the bone apatite-like crystals may be due to the precipitation of calcium and phosphate ions released from the dissolving ceramic crystals (the beta-TCP component dissolving preferentially to the HA component). Results from this study suggested that one of the means of controlling resorbability (in vivo dissolution) of BCP ceramic is by varying its beta-TCP/HA ratio.