Search

Biological apatite is an inorganic calcium phosphate salt in apatite form and nano size with a biological derivation. It is also the main inorganic component of biological hard tissues such as bones and teeth of vertebrates. Consequently, biological apatite has a wide application in dentistry and orthopedics by using as dental fillers and bone substitutes for bone reconstruction and regeneration. Given this, it is of great significance to obtain a comprehensive understanding of its physiochemical and biological properties. However, upon the previous studies, inconsistent and inadequate data of such basic properties as the morphology, crystal size, chemical compositions, and solubility of biological apatite were reported. This may be ascribed to the differences in the source of raw materials that biological apatite are made from, as well as the effect of the preparation approaches. Hence, this paper is to provide some insights rather than a thorough review of the physiochemical properties as well as the advantages and drawbacks of various preparation methods of biological apatite.

To evaluate the effect of intervention timing of Sr treatment on trabecular bone microstructure and mechanics.Ninety female rats were randomly divided into three batches with three groups in each batch. Each group was divided according to the initiation timing of vehicle or strontium compound (SrC), which was at week 0 (early), 4 (mid-term) and 8 (late) after the ovariectomy, respectively. The treatment lasted for 12 weeks. The trabecular bone biomechanical properties, trabecular bone tissue mechanical properties, trabecular bone microstructure, and bone remodeling were analyzed with mechanical testing, nanoindentation, microCT, and histomorphometry, respectively. The osteoblast and osteoclast phenotypic genes were analyzed with real-time polymerase chain reaction (PCR).Early and mid-term Sr treatment significantly increased biomechanical properties of trabecular bone, which was associated with increased microarchitecture parameters, increased bone formation parameters and up-regulation of osteoblast-related gene expression. Late Sr treatment failed to exert a beneficial effect on any of those parameters.The beneficial effect of Sr was dependent on the intervention timing in ovariectomized rats.

Chitosan-disulfide-conjugated LMW-PEI (CS-ss-PEI) was designed to combine the biocompatibility of chitosan and the gene delivery ability of polyethylenimine (PEI) using bio-reducible disulfide for bone morphogenetic protein (BMP2) gene delivery in mediating osteogenic differentiation. It was prepared by conjugating low molecular weight PEI (LMW-PEI) to chitosan through oxidization of thiols introduced for the formation of disulfide linkage. The structure, molecular weight and buffer capacity were characterized by Fourier transform infrared (FTIR), light scattering and acid–base titration, respectively. The reduction in molecular weight of CS-ss-PEI by the reducing agent indicated its bio-reducible property. With the increment in the LMW-PEI component, the copolymer showed increased DNA binding ability and formed denser nanocomplexes. CS-ss-PEI exhibited low cytotoxicity in COS-1, HepG2 and 293T cells over the different weight ratios. The transfection efficiency of CS-ss-PEI4 was significantly higher than that of PEI 25k and comparable with Lipofectamine in mediating luciferase expression. Its application for BMP2 gene delivery was confirmed in C2C12 cells by BMP2 expression. For inducing in vitro osteogenic differentiation, CS-ss-PEI4 mediated BMP2 gene delivery showed a stronger effect in MG-63 osteoblast cells and stem cells in terms of alkaline phosphatase activity and mineralization compared with PEI25k and Lipofectamine. This study provides a potential gene delivery system for orthopedic-related disease.

Study Design. A paired biomechanical study of pedicle screws augmented with bone cement in a human cadaveric and osteoporotic lumbar spine model. Objectives. To evaluate immediate strength and stiffness of pedicle screw fixation augmented with a novel bioactive bone cement in an osteoporotic spine model and compare it with polymethylmethacrylate (PMMA) cement. Summary of Background Data. A novel bioactive bone cement, containing nanoscale particles of strontium and hydroxyapatite (Sr-HA), can promote new bone formation and osteointegration and provides a promising reinforcement to the osteoporotic spine. Its immediate mechanical performance in augmenting pedicle screw fixation has not been evaluated. Methods. Two pedicle screws augmented with Sr-HA and PMMA cement were applied to each of 10 isolated cadaveric L3 vertebrae. Each screw was subjected to a toggling test and screw kinematics were calculated. The pedicle screw was subjected to a pullout test until failure. Finally, the screw coverage with cement was measured on computed tomographic images. Results. Screw translations in the toggling test were consistently larger in the Sr-HA group than in the PMMA group (1.4 ± 1.2 mm vs. 1.0 ± 1.1 mm at 1000 cycles). The rotation center was located closer to the screw tip in the Sr-HA group (19% of screw length) than in the PMMA group (37%). The only kinematic difference between Sr-HA and PMMA cements was the screw rotation at 1000 cycles (1.5° ± 0.9° vs. 1.3° ± 0.6°; P = 0.0026). All motion parameters increased significantly with more loading cycles. The pullout force was higher in the PMMA group than the Sr-HA group (1.40 ± 0.63 kN vs. 0.93 ± 0.70 kN), and this difference was marginally significant (P = 0.051). Sr-HA cement covered more of the screw length than PMMA cement (79 ± 19% vs. 43 ± 19%) (P = 0.036). Conclusion. This paired-design study identified some subtle but mostly nonsignificant differences in immediate biomechanical fixation of pedicle screws augmented with the Sr-HA cement compared with the PMMA cement.

The deposition of hydroxyapatite [Ca 1 0 (PO 4 ) 6 (OH) 2 ] coatings on bioactive glass (45S5) arid on inert ceramic substrates (fused SiO 2 and Al 2 O 3 ) from aqueous solutions containing calcium and phosphate ions was investigated under hydrothermal conditions at temperatures between 90 °C and 150 °C. Rapid deposition of hydroxyapatite coatings was achieved on 45S5 glass at pH = 12.5. Growth of the hydroxyapatite coating was preceded by the formation of an amorphous CaO-SiO 2 layer with a thickness of -2 μm. The hydroxyapatite coating grew rapidly, with the thickness increasing linearly with time, and with preferred alignment of the c-axis of the crystals perpendicular to the glass surface. Under the same conditions, no hydroxyapatite deposition was observed on fused SiO 2 and Al 2 O 3 . Successful deposition of hydroxyapatite coatings on Al 2 O 3 was achieved from an aqueous solution of calcium and phosphate ions containing EDTA disodium salt as a chelating agent and hydrogen peroxide. The deposition was strongly dependent on the pH of the solution. Uniform deposition was achieved at pH = 9.8. Initial formation of the coating occurred with the hydroxyapatite crystals aligned parallel to the Al 2 O 3 surface but the orientation soon changed to give growth with the c-axis perpendicular to the surface. The extent of the orientation increased with time to give nearly perpendicular orientation after -12 h.

In this study, the effects of a series of strontium (Sr)-substituted HA ceramics (0, 1, 5, and 10 mol % Sr substitution) were tested on their physical and biological properties. The crystal structure, composition, and solubility were investigated by TEM, XRD, and solid titration solubility isotherms, respectively. In addition, rat MSCs were cultured with culture media containing ions released from the strontium-substituted HA ceramics as they dissolved. MTT test, alkaline phosphatase activity, and osteoblast transcription factor gene (cbfa1) expression were conducted at different time points. Our results suggested that HA with Sr substitution may change its physical properties, especially its solubility, and consequently enhance undifferentiated MSCs into osteoblast lineage. The results from this and the previous study suggested that 5-10 mol % Sr substitution into HA may be a suitable choice for its use in bone regenerative field.

Osteoporosis is a disease attributed to an imbalance in communication between osteoblasts and osteoclasts, possibly arising from a locally acidic microenvironment which hinders normal cell function. However, to date, little or no attention has been paid to these cells' milieu in respect of implant materials. Although it has been claimed for a few biomaterials that they stimulate bone formation, seldom has their surface behavior been invoked to explain behavior. With degradation, ion concentrations and pH at the material's surface must vary and thus may affect osteoblast response directly. On degradation of a recently developed biomaterial, Sr-containing CaSiO3, the interfacial pH was found to be appreciably higher than that of the bulk medium and the "standard" physiological value of 7.4. At these high values (pH > 8), both the proliferation and alkaline phosphatase (ALP) activity of osteoblasts was significantly enhanced, with a maximum response at 10% Sr substitution for Ca. This shows that the chemistry of the solid-liquid interface is a critical factor in bone regeneration, although this has generally been overlooked. Thus, the interfacial pH in particular is to be considered, rather than the bulk value, and this may be of importance in many related contexts in bone-tissue engineering.

Poly (methyl methacrylate) (PMMA) bone cement is widely used in vertebral body augmentation procedures such as vertebroplasty and balloon kyphoplasty. Filling high modulus PMMA increases the modulus of filled verterbra, increasing the risk of fracture in the adjacent vertebra. On the other hand, in porous PMMA bone cements, wear particle generation and deterioration of mechanical performance are the major drawbacks. This study adopts a new approach by utilizing linoleic acid coated strontium substituted hydroxyapatite nanoparticle (Sr-5 HA) and linoleic acid as plasticizer reducing bone cement's modulus with minimal impact on its strength. We determined the compressive strength (UCS) and modulus (Ec), hydrophobicity, injectability, in vitro bioactivity and biocompatibility of this bone cement at different filler and linoleic acid loading. At 20 wt % Sr5-HA incorporation, UCS and Ec were reduced from 63 ± 2 MPa, 2142 ± 129 MPa to 58 ± 2 MPa, 1785 ± 64 MPa, respectively. UCS and Ec were further reduced to 49 ± 2 MPa and 774 ± 70 MPa respectively when 15 v/v of linoleic acid was incorporated. After 7 days of incubation, pre-osteoblast cells (MC3T3-E1) attached on 20 wt % Sr5-HA and 20 wt % Sr5-HA with 15 v/v of linoleic acid group were higher (3.73 ± 0.01 x 10⁴, 2.27 ± 0.02 x 10⁴) than their PMMA counterpart (1.83 ± 0.04 x 10⁴). Incorporation of Sr5-HA with linoleic acid in monomer phase is more effective in reducing the bone cement's stiffness than Sr5-HA alone. Combination of low stiffness and high mechanical strength gives the novel bone cement the potential for use in vertebroplasty cement applications.

Novel bioactive bis-GMA-based resin composites were successfully developed by incorporating hydroxyapatite (HA) whiskers in the polymeric matrix. The whiskers had good dispersibility and wettability with bis-GMA-based polymer, showing good bonding with the matrix, which conferred good reinforcement. The mechanical properties of the composites were significantly enhanced when compared with the particulate filler. The morphology change of HA did not cause obvious variations in the proliferation and viability of L929 cells and the apatite-forming ability of the composites in SBF. The in vitro cytotoxicity of the composites was depressed by addition of hydroxyapatite filing materials. Such a favorable response indicated an important similarity in surface chemistry of the HA filler, and HA whiskers appeared to have potential as most promising reinforcements for resin-based polymers.

The ability to trigger the formation of apatite from a supersaturated solution has been widely used to imply the bioactivity of an implant in vivo. However, the method itself may provide at best incomplete information, primarily because it is determined only by solution supersaturation, irrespective of biological processes. Bone regeneration is triggered mainly by the vitality of osteoblasts, and regulated by the expression of growth factors such as oestrogen, parathyroid hormone and bone morphogenetic proteins, while ions or other species released from an implant may affect the expression of such growth factors, and so bone resorption or formation. The misinterpretation of the outcome of such tests must result in misunderstanding of the true effects and behaviour of materials intended for use in embedded biological contexts. Thus, the underlying and motivating hypothesis needs to be carefully reconsidered, along with the results of all work founded on the concept. It would seem that it is only viable to test using osteoblasts, whether in vivo or in vitro.

Phase-pure strontium silicate (SrSiO(3)) powders were synthesized by chemical precipitation method. In vitro bioactivity of the powders were evaluated by examining the hydroxyapatite forming ability on their surface soaking simulated body fluid for various periods. The results showed that SrSiO(3) could induce hydroxy carbonate apatite formation after soaking for 7 days. Both L929 and rabbit bone marrow stromal cells (rMSCs) were used to test the in vitro cytocompatibility of SrSiO(3). L929 culture experiment showed that the ionic product of SrSiO(3) did not exhibit cytotoxicity except at high ion concentrations (Si 3.75 mM and Sr 0.12 mM). Moreover, at certain ion concentrations (Si 1.87-0.12 mM and Sr 0.12-3.75 x 10(-3) mM), the ionic product of SrSiO(3) stimulated the proliferation of rMSCs. All the results indicated that SrSiO(3) might be used as a new bioactive material for bone regeneration applications.

Boron plays important roles in many life processes including embryogenesis, bone growth and maintenance, immune function and psychomotor skills. Thus, the delivery of boron by the degradation of borate glass is of special interest in biomedical applications. However, the cytotoxicity of borate glass which arises with the rapid release of boron has to be carefully considered. In this study, it was found that the incorporation of strontium into borate glass can not only moderate the rapid release of boron, but also induce the adhesion of osteoblast-like cells, SaOS-2, thus significantly increasing the cyto-compatibility of borate glass. The formation of multilayers of apatite with porous structure indicates that complete degradation is optimistic, and the spread of SaOS-2 covered by apatite to form a sandwich structure may induce bone-like tissue formation at earlier stages. Therefore, such novel strontium-incorporated borosilicate may act as a new generation of biomaterial for bone regeneration, which not only renders boron as a nutritious element for bone health, but also delivers strontium to stimulate formation of new bones. © 2009 The Royal Society., link_to_OA_fulltext

The determination of the solubility of calcium phosphates by the conventional large excess of solid method has been demonstrated to be inappropriate. The problem lies in incongruent dissolution, leading to phase transformations, and lack of detailed solution equilibria: all calculations have been based on simplifications, which are only crudely approximate. The absolute solid-titration approach shows excellent reliability and reproducibility. Using solid titration, the true solubility isotherm of hydroxyapatite (HAp) has been found to lie substantially lower than previously reported. In addition, contrary to wide belief, dicalcium phosphate dihydrate (DCPD) is not the most stable phase below pH ∼4.2, where calcium-deficient HAp is less soluble. The misunderstanding here arises from the metastability of DCPD, which nucleates much more easily than HAp at low pH. Such results indicate that the Ca−P system is in need of complete reappraisal. The solid-titration method can be extended to other complex systems.

Strontium-containing hydroxyapatite/polyetheretherketone (Sr-HA/PEEK) composites were developed as alternative materials for load-bearing orthopaedic applications. The amount of strontium-containing hydroxyapatite (Sr-HA) incorporated into polyetheretherketone (PEEK) polymer matrix ranged from 15 to 30 vol% and the composites were successfully fabricated by compression molding technique. This study presents the mechanical properties and in vitro human osteoblast-like cell (MG-63) response of the composite material developed. The bending modulus and strength of Sr-HA/PEEK composites were tailored to mimic human cortical bone. PEEK reinforced with 25 and 30 vol% Sr-HA exhibited bending modulus of 9.6 and 10.6 GPa, respectively; alternatively, the bending strengths of the composites were 93.8 and 89.1 MPa, respectively. Based on the qualitative comparison of apatite formation in SBF and quantitative measurement of MG-63-mediated mineralization in vitro, the Sr-HA/PEEK composite was proven to outperform HA/PEEK in providing bioactivity. However, no difference was found in the trend of cell proliferation and alkaline phosphatase activity between different composites. Strontium, in the form of strontium-containing hydroxyapatite (Sr-HA), was confirmed to enhance bioactivity in the PEEK composites.

High aspect ratio strontium hydroxyapatite nanorod significant enhances the mechanical strength of bioactive bone cement, due to its fiber like nature. However, incompatibility between resin matrix and strontium hydroxyapatite (Sr-HA) reduce the maximum filler loading and excessive strontium release leads to cytotoxicity problem. The aim of this study is to design a high aspect ratio hydroxyapatite nanorod with good resin compatibility and acceptable strontium release rate.

Three-dimensional macroporous scaffolds with the pore size of 200-500 mum were fabricated by replication method using bioactive borosilicate glass from Na(2)O-K(2)O-MgO-CaO-SiO(2)-P(2)O(5)-B(2)O(3) system. The effects of the strength of the strut in reticulated scaffold, as well as the geometrical parameter of the scaffold on the strength of reticulated scaffold were investigated. Scanning electron microscope (SEM) and X-ray diffraction (XRD) results show that the solidified glass struts in the reticulated scaffold could be obtained through a sufficient vicious flow of glass, during the fabrication. By increasing the solid content in slurries, from which the scaffold was made, the load-bearing units of the reticulated scaffold switch from struts to the walls between the pores, and the compressive strength dramatically climbs higher than the theoretical strength calculated by Gibson model. In particular, the compressive strength of the reticulated scaffold, as high as approximately 10 MPa with the porosity of approximately 70%, is close to the reported compressive values of human cancellous bone. This indicates the bioactive borosilicate glass-based scaffold is a promising candidate for bone tissue engineering.

In this article, we report a novel switch property of conducting polypyrrole nanotube arrays (CPNAs) on biomedical titanium, in which the nanotubular structure can be reversibly switched between open and closed states by applying switch-open/close potentials in situ. We propose a new insight into the study of reversible tubular switches in CPNAs.

The effect of local pH on bone regeneration has never been properly studied or discussed. However, using a microelectrode, the pH on the surface of implant materials, rather than in the bulk, is measurable so that the biological response based on the local environment can be studied. It was found that the osteoblast viability was significantly enhanced with an increase of pH, to an optimum level at ∼pH 8–8.5; in contrast, the activity fell markedly below pH 6. The effect of strontium on osteoblast proliferation was further increased at pH ∼8, suggesting a possible new approach for enhancing its activity in the treatment of osteoporosis. No stimulation of osteoblast proliferation was found for boron at normal physiological pH but, surprisingly, such an effect was found at pH 8.5. For the degradation of strontium-doped borosilicate, the ambient alkaline pH not only enhanced the activity of strontium and boron, but also facilitated the nucleation of apatite, as indicated by the newly formed bony tissue. Consequently, appropriately designed biomaterials, which create such an ideal ambient alkaline environment for bone regeneration, may be crucial aspects for bone substitutes.

Porous scaffolds of a borate-based glass (composition in mol%: 6Na2O, 8K2O, 8MgO, 22CaO, 36B2O3, 18SiO2, 2P2O5), with interconnected porosity of approximately 70% and pores of size 200-500 microm, were prepared by a polymer foam replication technique. The degradation of the scaffolds and conversion to a hydroxyapatite-type material in a 0.02 M K2HPO4 solution (starting pH = 7.0) at 37 degrees C were studied by measuring the weight loss of the scaffolds, as well as the pH and the boron concentration of the solution. X-ray diffraction, scanning electronic microscopy and energy dispersive x-ray analysis showed that a hydroxyapatite-type material was formed on the glass surface within 7 days of immersion in the phosphate solution. Cellular response to the scaffolds was assessed using murine MLO-A5 cells, an osteogenic cell line. Scanning electron microscopy showed that the scaffolds supported cell attachment and proliferation during the 6 day incubation. The results indicate that this borate-based glass could provide a promising degradable scaffold material for bone tissue engineering applications.

Background The precise etiology of knee osteoarthritis (KOA) pain remains highly controversial and there is no known effective treatment. Due to the known and suggested effects of neuropeptide Y (NPY) on pain, we have sought to investigate the relationship between the concentration of NPY in synovial fluid of knee, pain of KOA, and structural severity of KOA. Methods One hundred KOA patients and twenty healthy participants (control group) were recruited. The pain and the radiographic grade of KOA were assessed separately by Hideo Watanabe’s pain score and Tomihisa Koshino’s scoring system. Synovial fluid of knee from all participants was collected with arthrocentesis. Radioimmunoassay was used to examine the concentration of NPY in synovial fluid of knee. Results Concentrations of NPY in synovial fluid were significantly higher in KOA patients (124.7 ± 33.4 pg/mL) compared with controls (64.8 ± 26.3 pg/mL) (p = 0.0297). According to Hideo Watanabe’s pain score, 100 KOA patients were divided into 5 subgroups: no pain (n = 12), mild pain (n = 25), moderate pain (n = 37), strong pain (n = 19) and severe pain (n = 7). Within the KOA group, significantly higher concentrations of NPY were found in each subgroup as pain intensified (no pain 81.4 ± 11.7 pg/mL, mild pain 99.1 ± 23.2 pg/mL, moderate pain 119.9 ± 31.5 pg/mL, strong pain 171.2 ± 37.3 pg/mL and severe pain 197.3 ± 41.9 pg/mL). Meanwhile, according to Tomihisa Koshino’s scoring system, 100 KOA patients were divided into 3 subgroups: early stage (n = 30), middle stage (n = 53), advanced stage (n = 17). Concentrations of NPY in middle and advanced stage groups of KOA patients were significant higher than early stage group of KOA patients (early stage 96.4 ± 27.1 pg/mL, middle stage 153.3 ± 16.9 pg/mL, advanced stage 149.5 ± 36.7 pg/mL) (p = 0.0163, p = 0.0352). Concentrations of NPY in advanced stage group of KOA patients has no significant difference compare with middle stage group of KOA patients (p = 0. 2175). Conclusions This study demonstrated the presence and variation of concentrations of NPY in the KOA joint fluid, suggesting a role for NPY as a putative regulator of pain transmission and perception in KOA pain. Electronic supplementary material The online version of this article (doi:10.1186/1471-2474-15-319) contains supplementary material, which is available to authorized users.