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Bone regeneration using synthetic materials has a high rate of surgical site infection, resulting in severe pain for patients and often requiring revision surgery. We propose Ag3PO4-based surface modification and structural control of scaffolds for preventing infections in bone regeneration. We demonstrated the differences in toxicity and antibacterial activity between in vitro and in vivo studies and determined the optimal silver content in terms of overall anti-infection effects, bone regeneration, toxicity, and pigmentation. A honeycomb structure comprising osteoconductive and resorbable carbonate apatite (CAp) was used as the base scaffold. CAp in the scaffold surface was partially replaced with different concentrations of Ag3PO4 via controlled dissolution-precipitation reactions in an AgNO3 solution. Both bone regeneration and infection prevention were achieved at 860-2300 ppm of silver. Despite the absence of Ag3PO4, honeycomb scaffolds were less susceptible to infection, even under conditions where infection occurs in clinically used three-dimensional porous scaffolds. Regardless of in vitro cytotoxicity at >5200 ppm of silver, increasing the silver content to 21,000 ppm did not adversely affect in vivo bone formation and scaffold resorption or cause acute systemic toxicity. Rather, bone formation was enhanced with 5200 ppm of silver. However, pigmentation was observed at that concentration. Hence, we concluded that the optimal silver concentration range is 860-2300 ppm for anti-infective and pigmentation-free bone regeneration. Bone regeneration was achieved via surface modification, resulting in the rapid release of silver ions immediately after implantation, followed by gradual release over several months. The scaffold structure may also aid in preventing bacterial growth within the scaffolds.
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Both the composition and architecture of artificial bone govern bone regeneration. Herein, carbonate apatite (CAp), which has a similar mineral composition to bone, was prepared by immersing calcium carbonate (CaCO3) in a phosphate solution with varying acidification levels (pH 6.0) to pH 8.9, to reveal the influence of pH on the composition and architecture of the resultant CAp granules. The composition, crystal morphology, and architecture of resultant CAp granules was well-characterized by X-ray diffraction, scanning electron microscopy, mercury intrusion porosimetry and so on. Consequently, the rate of compositional transformation from CaCO3 to CAp was much higher at pH 6.0 and pH 7.0 than pH 8.0 and pH 8.9. The pH of the phosphate solution did not affect the macroarchitecture of the resultant CAp granules. In contrast, the composition, crystal morphology, microarchitecture, and degradation behavior of the resultant CAp granules were affected by pH of the phosphate solution. In particular, the open-pore distributions and volumes of the CAp granules prepared at pH 6.0-8.9 were changed to reflect the microarchitecture of the samples. Therefore, this study revealed that the pH-controlled elution precipitation reaction is useful for controlling the composition, crystal morphology, microarchitecture, and degradation behavior of the resultant CAp, while preserving its macroarchitecture. Our findings provide fundamental insights into the design of artificial bones for bone regeneration.
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Titanium with apatite-forming ability as well as antibacterial activity is useful as a component of antibacterial dental implants. When Ti was subjected to hydrogen peroxide (H2O2), copper acetate (Cu(OAc)2), and heat (H2O2-Cu(OAc)2-heat) treatments, a network structure of anatase and rutile titanium dioxide (TiO2) and fine copper oxide (CuO) particles was formed on the Ti surface. The resulting samples accumulated a dense and uniform apatite layer on the surface when incubated in simulated body fluid and showed enhanced antibacterial activity against Escherichia coli and Staphylococcus aureus under visible-light irradiation. Electron spin resonance spectra of H2O2-Cu(OAc)2-heat-treated samples showed that hydroxyl radicals (·OH) were generated from the samples, and the concentration of ·OH increased with increasing Cu concentration of the Cu(OAc)2 solution. The enhanced antibacterial activity of these samples under visible-light irradiation may be attributable to the generation of ·OH from samples. These results suggest that Ti implants obtained using H2O2-Cu(OAc)2-heat treatments and subjected to regular or on-demand visible-light irradiation may provide a decreased risk of peri-implantitis.
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This study aimed to clarify the effects of multiple firings on the translucency, crystal structure, and mechanical strength of highly translucent zirconia. Four types of highly translucent zirconia (LAVA Esthetic, LAVA Plus, KATANA Zirconia STML, and KATANA Zirconia HTML) were fired three times at three different temperatures, and the translucency, crystal structure, and flexural strength were evaluated before and after firing. The translucency was statistically compared using repeated-measures analysis of variance; the zirconia phase composition was assessed using X-ray diffraction followed by Rietveld analysis; and the biaxial flexural strength was assessed using Weibull analysis. The translucency of LAVA Esthetic and KATANA Zirconia HTML decreased significantly after firing, and the crystal composition of LAVA Plus and KATANA Zirconia HTML changed after multiple firings, whereas multiple firings did not affect the biaxial flexural strength of any samples. Thus, multiple firings may affect the optical properties of highly translucent zirconia.
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Materiales Dentales , Resistencia Flexional , Materiales Dentales/química , Ensayo de Materiales , Circonio/química , Cerámica/química , Propiedades de SuperficieRESUMEN
Implant-associated infections are threatening and devastating complications that lead to bone destruction and loss. As a smooth surface is suitable for inhibiting bacterial adhesion, endowing antibacterial activity to the Ti surface without any structural changes in the surface topography is an effective strategy for preventing infection. The thin film on the Ti-6Al-4 V surface was functionalized to endow antibacterial activity by immersion in a Cu(OH)2 solution. The resulting surface maintains the surface topography with a surface roughness of 0.03 µm even after the immersion in the Cu(OH)2 solution. Moreover, Cu was detected at approximately 10 atom% from the surface and was present up to a depth of 30 nm of thin film. In vitro experiments revealed that the resulting surface exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus and allowed the cellular proliferation, differentiation, and calcification of MC3T3-E1 cells. Furthermore, in vivo experiments determined that the presence of Cu in the thin film on the Ti-6Al-4 V surface led to no inflammatory reactions, including bone resorption. Thus, immersion in a Cu(OH)2 solution incorporates and immobilizes Cu into the thin film on the Ti-6Al-4 V surface without any structural alternations in the surface topography, and the resulting smooth surface exhibits antibacterial activity and osteogenic cell compatibility without cytotoxicity or inflammatory reactions. Our findings provide fundamental insights into the surface design of Ti-based medical devices, to achieve bone reconstruction and infection prevention.
Passivation of Ti-6Al-4V in Cu(OH)2 solution endowed smooth thin film with antibacterial activity and osteogenic cell compatibility for potentially achieving both bone reconstruction and infection prevention.
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Ti surfaces must exhibit antibacterial activity without cytotoxicity to promote bone reconstruction and prevent infection simultaneously. In this study, we employed a two-step electrochemical treatment process, namely, microarc oxidation (MAO) and cathodic electrochemical deposition (CED), to modify Ti surfaces. During the MAO step, a porous TiO2 (pTiO2) layer with a surface roughness of approximately 2.0 µm was generated on the Ti surface, and in the CED step, Cu was deposited onto the pTiO2 layer on the Ti surface, forming Cu@pTiO2. Cu@pTiO2 exhibited a similar structure, adhesion strength, and crystal phase to pTiO2. Moreover, X-ray photoelectron spectroscopy (XPS) confirmed the presence of Cu in Cu@pTiO2 at an approximate concentration of 1.0 atom %. Cu@pTiO2 demonstrated a sustained release of Cu ions for a minimum of 28 days in a simulated in vivo environment. In vitro experiments revealed that Cu@pTiO2 effectively eradicated approximately 99% of Staphylococcus aureus and Escherichia coli and inhibited biofilm formation, in contrast to the Ti and pTiO2 surfaces. Moreover, Cu@pTiO2 supported the proliferation of osteoblast-like cells at a rate comparable to that observed on the Ti and pTiO2 surfaces. Similar to pTiO2, Cu@pTiO2 promoted the calcification of osteoblast-like cells compared with Ti. In summary, we successfully conferred antibacterial and pro-osteogenic activities to Ti surfaces without inducing cytotoxic effects or structural and mechanical alterations in pTiO2 through the application of MAO and CED processes. Moreover, we found that the pTiO2 layer promoted bacterial growth and biofilm formation more effectively than the Ti surface, highlighting the potential drawbacks of rough and porous surfaces. Our findings provide fundamental insights into the surface design of Ti-based medical devices for bone reconstruction and infection prevention.
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Cobre , Titanio , Cobre/farmacología , Cobre/química , Porosidad , Titanio/farmacología , Titanio/química , Antibacterianos/farmacología , Antibacterianos/químicaRESUMEN
Polymethyl methacrylate (PMMA) bone cement is widely used to relieve pain caused by metastatic bone tumors. We previously found that PMMA bone cement containing 15 mass% or more of TiO2 showed good apatite-forming ability, and 25 mass% or more of Fe3O4 generated sufficient heat for hyperthermia under an alternating current (AC) magnetic field. In this study, the cytocompatibility of PMMA bone cement with Fe3O4:TiO2 weight ratios of 25:15 (F25T15-3/2-42) and 30:15 (F30T15-3/2-42) was evaluated using osteoblastic cells (MC3T3-E1). The proliferation and differentiation of MC3T3-E1 cells were suppressed for F25T15-3/2-42 and F30T15-3/2-42 compared to PMMA bone cement without Fe3O4 and TiO2 (F0T0-3/2-42). The release of methyl methacrylate (MMA) monomers from F25T15-3/2-42 and F30T15-3/2-42 at 7 days was about 33 and 50 times higher than that from F0T0-3/2-42, respectively. The remarkable release of MMA monomers from F25T15-3/2-42 and F30T15-3/2-42 may be responsible for the suppressed proliferation and differentiation of MC3T3-E1 cells. The release of MMA monomers was not reduced when the MMA/PMMA weight ratio was decreased from 3/2 to 1/1, however, it was significantly reduced by increasing the content of benzoyl peroxide (BPO) and N, N-dimethyl-p-toluidine (DMPT) to 8 and 4 mass% against MMA, respectively. Proliferation and differentiation of MC3T3-E1 cells on PMMA-type cements containing Fe3O4 and TiO2 with increased BPO and DMPT contents need to be investigated in the future; however, our findings will be useful for designing PMMA cements for the hyperthermic treatment of metastatic bone tumors.
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Neoplasias Óseas , Polimetil Metacrilato , Humanos , Cementos para Huesos/uso terapéutico , Metilmetacrilato , Diferenciación Celular , Neoplasias Óseas/terapia , Proliferación Celular , Ensayo de MaterialesRESUMEN
Improving the damage tolerance and reliability of ceramic artificial bone materials, such as sintered bodies of hydroxyapatite (HAp), that remain in vivo for long periods of time is of utmost importance. However, the intrinsic brittleness and low damage tolerance of ceramics make this challenging. This paper reports the synthesis of highly damage tolerant calcium phosphate-based materials with a bioinspired design for novel artificial bones. The heat treatment of isophthalate ion-containing octacalcium phosphate compacts in a nitrogen atmosphere at 1000°C for 24 h produced an HAp/ß-tricalcium phosphate/pyrolytic carbon composite with a brick-and-mortar structure (similar to that of the nacreous layer). This composite exhibited excellent damage tolerance, with no brittle fracture upon nailing, likely attributable to the specific mechanical properties derived from its unique microstructure. Its maximum bending stress, maximum bending strain, Young's modulus, and Vickers hardness were 11.7 MPa, 2.8 × 10â2, 5.3 GPa, and 11.7 kgf/mm2, respectively. The material exhibited a lower Young's modulus and higher fracture strain than that of HAp-sintered bodies and sintered-body samples prepared from pure octacalcium phosphate compacts. Additionally, the apatite-forming ability of the obtained material was confirmed in vitro, using a simulated body fluid. The proposed bioinspired material design could enable the fabrication of highly damage tolerant artificial bones that remain in vivo for long durations of time.
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Octacalcium phosphate (OCP) is a layered compound capable of incorporating carboxylate ions within its interlayer structure. In this study, we successfully synthesised OCP with incorporated 3,3'-dithiodipropionate ions. Our finding is beneficial for the development of novel OCP-based materials with dynamic properties derived from disulfide bonds.
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Dental implants made of titanium (Ti) are used in dentistry, but peri-implantitis is a serious associated problem. Antibacterial and osteoconductive Ti dental implants may decrease the risk of peri-implantitis. In this study, titania (TiO2) co-doped with silver (Ag) at 2.5 at.% and copper (Cu) at 4.9 at.% was formed on Ti substrates via chemical and thermal treatments. The Ag and Cu co-doped TiO2 formed apatite in a simulated body fluid, which suggests osteoconductivity. It also showed antibacterial activity against Escherichia coli, which was enhanced by visible-light irradiation. This enhancement might be caused by the synergistic effect of the release of Ag and Cu and the generation of â¢OH from the sample. Dental implants with such a Ag and Cu co-doped TiO2 formed on their surface may reduce the risk of peri-implantitis.
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Implantes Dentales , Periimplantitis , Humanos , Titanio/química , Plata/farmacología , Plata/química , Cobre/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Escherichia coliRESUMEN
The composition of carbonate apatite (CO3 Ap) aids bone regeneration. Other features, such as porosity and pore interconnectivity of artificial bone, also govern bone regeneration. In general, a trade-off exists between the porosity and mechanical strength of artificial bone. Therefore, this suggests that the interconnected pores in the ant-nest-type porous (ANP) structure of artificial bone accelerate bone regeneration by minimizing the sacrifice of mechanical strength. The unique structure of polyurethane foam has the potential to endow CO3 Ap with an ANP structure without forming excess pores. This study investigated the efficacy of polyurethane foam as a porogen in providing ANP structure to CO3 Ap artificial bone. The polyurethane foam was completely decomposed by sintering and the resulting CO3 Ap displayed ANP structure with a compressive strength of approximately 15 MPa. Furthermore, in vivo experiments revealed that the migration of cells and tissues into the interior of CO3 Ap through the interconnected pores accelerated bone regeneration in the ANP-structured CO3 Ap. Thus, this indicates that using polyurethane foam as a porogen endows the CO3 Ap artificial bone with an ANP structure that accelerates bone regeneration.
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Apatitas , Sustitutos de Huesos , Andamios del Tejido , Apatitas/farmacología , Apatitas/química , Porosidad , Andamios del Tejido/químicaRESUMEN
INTRODUCTION: Cases of intractable dental implant require vertical bone augmentation; however, the predicted bone height and volume are difficult to obtain. In vertical bone augmentation, the contact surface between the scaffold and the bone is limited to the bottom face of the scaffold. Furthermore, the strength decrease caused by scaffold resorption leads to collapse of the augmented site, leading to a decrease in the bone volume and height. OBJECTIVES: To promote bone ingrowth, we fabricated carbonate apatite (i.e., bone mineral) honeycomb (HC) scaffolds with uniaxial channels vertically penetrating the scaffold. Furthermore, we controlled the scaffold resorption rate, eventually the endurability for compression, and the bone height and volume by controlling the strut thickness. METHODS: The channel aperture was controlled to be 230-260 µm to promote bone ingrowth. Furthermore, the strut thicknesses of the HC scaffolds were adjusted to 100, 200, and 300 µm to control the scaffold resorption; these scaffolds were designated as HC100, HC200, and HC300, respectively. RESULTS: At 4 weeks post-implantation on rabbit calvarium, all scaffolds had already vertically augmented new bone close to the top surface of the scaffold. In the following 8 weeks, the height and amount of new bone in all scaffolds increased. Notably, HC300 was resorbed synchronously with new bone formation, allowing it to endure the compression from the fasciae for 12 weeks post-implantation. Furthermore, HC300 formed larger-diameter blood vessels than those of HC100 and HC200. CONCLUSION: The HC scaffolds surpassed the various combined scaffolds and growth factors or stem cells in the ability for vertical bone augmentation. Thus, the HC structure is inherently suitable for vertical bone augmentation. Notably, the HC scaffolds with 300-µm-thick struts enhanced both new bone formation and angiogenesis. This study revealed a structurally suitable design for achieving an outstanding outcome in vertical bone augmentation.
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Aumento de la Cresta Alveolar , Animales , Conejos , CráneoRESUMEN
Osteomyelitis is a potentially devastating inflammatory bone disease that leads to bone destruction and loss. Treatment of osteomyelitis requires the removal of residual bacteria as well as osteogenesis with angiogenesis at the site of treatment. Use of an appropriate amount of copper (Cu) in treatment scaffolds may achieve these goals without the risk of toxicity. In this study, the surface of the carbonate apatite honeycomb scaffold was functionalized with Cu through a dissolution-precipitation reaction. The resulting scaffolds retained the honeycomb structure after immersion in CuCl2 solution, and Cu was precipitated on the surface as libethenite [Cu2(OH)PO4]. The surface Cu concentration was controlled by the concentration of the CuCl2 solution. Scaffolds with a surface Cu concentration of 23.8 wt% exhibited antibacterial and cytotoxic effects, whereas those with concentrations of ≤4.6 wt% exerted antibacterial effects without negatively affecting the cellular adhesion, proliferation, differentiation, and calcification of osteoblast-like cells. Furthermore, scaffolds with a surface Cu concentration of 4.6 wt% Cu inhibited bacterial growth for at least 28 days and displayed proangiogenic and pro-osteogenic activities in vivo. These data confirm the success in functionalizing scaffolds with Cu that may be utilized as an innovative osteomyelitis therapy.
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Células Madre Mesenquimatosas , Osteomielitis , Antibacterianos/farmacología , Apatitas , Cobre/química , Humanos , Osteogénesis , Osteomielitis/tratamiento farmacológico , Andamios del Tejido/químicaRESUMEN
Octacalcium phosphate (OCP) belongs to a family of calcium phosphate compounds. OCP has unique crystal-chemical properties; among calcium phosphate compounds, only OCP can incorporate carboxylate ions into its crystal lattice. An OCP with incorporated carboxylate ions is called an OCP carboxylate (OCPC). OCPCs are investigated for applications in novel adsorbents, electrochemical devices, and biomaterials. Several wet methods are available for the synthesis of OCPCs, and the characteristics and advantages of each method are explained. Representative characterization methods, i.e. X-ray diffraction and Fourier transform infrared spectroscopy, used for the detection of carboxylate ion incorporation into the OCP interlayers are explained. Various carboxylic acids can be incorporated into OCP, and these types of carboxylic acid are presented with reference to the latest research results. The incorporation of carboxylate ions into OCP represents a modification of the OCP crystal at the molecular level and can impart various functions. Challenging physicochemical and biomaterial applications of OCPCs are thus introduced, although they are still in the research phase. Finally, future perspectives and challenges for OCPC research are described.
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Granular porous calcium phosphate scaffolds are used for bone regeneration in dentistry. However, in conventional granules, the macropore interconnectivity is poor and has varying size. Herein, we developed a productive method for fabricating carbonate apatite honeycomb granules with uniformly sized macropores based on extrusion molding. Each honeycomb granule possesses three hexagonal macropores of â¼290 âµm along its diagonal. Owing to these macropores, honeycomb granules simultaneously formed new and mature bone and blood vessels in both the interior and exterior of the granules at 4 weeks after implantation. The honeycomb granules are useful for achieving rapid osteogenesis and angiogenesis.
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Porous architecture in bone substitutes, notably the interconnectivity of pores, is a critical factor for bone ingrowth. However, controlling the pore interconnectivity while maintaining the microarchitecture has not yet been achieved using conventional methods, such as sintering. Herein, we fabricated a porous block using the crystal growth of calcium sulfate dihydrate, and controlled the pore interconnectivity by limiting the region of crystal growth. The calcium sulfate dihydrate blocks were transformed to bone apatite, carbonate apatite (CO3Ap) through dissolution-precipitation reactions. Thus, CO3Ap blocks with 15% and 30% interconnected pore volumes were obtained while maintaining the microarchitecture: they were designated as CO3Ap-15 and CO3Ap-30, respectively. At 4 weeks after implantation in a rabbit femur defect, new bone formed throughout CO3Ap-30, whereas little bone was formed in the center region of CO3Ap-15. At 12 weeks after implantation, a large portion of CO3Ap-30 was replaced with new bone and the boundary with the host bone became blurred. In contrast, CO3Ap-15 remained in the defect and the boundary with the host bone was still clear. Thus, the interconnected pores promote bone ingrowth, followed by replacement of the material with new bone. These findings provide a useful guide for designing bone substitutes for rapid bone regeneration.
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The porous architecture of artificial bones plays a pivotal role in bone ingrowth. Although salt leaching methods produce predictable porous architectures, their application in the low-temperature fabrication of ceramics remains a challenge. Carbonate apatite (CO3 Ap) blocks with three ranges of pore sizes: 100-200, 200-400, and 400-600 µm, were fabricated from CaCO3 blocks with embedded Na2 HPO4 crystals as a porogen and accelerator for CaCO3 -to-CO3 Ap conversion. CaCO3 blocks were obtained from Ca(OH)2 compacts with Na2 HPO4 by CO2 flow at 100% humidity. When carbonated under 100% water humidity, the dissolution of Na2 HPO4 and the formation of hydroxyapatite were observed. Using 90% methanol and 10% water were beneficial in avoiding the Na2 HPO4 consumption and generating the metastable CaCO3 vaterite, which was rapidly converted into CO3 Ap in a Na2 HPO4 solution in 7 days. For the histological evaluation, the CO3 Ap blocks were implanted in rabbit femur defects. Four weeks after implantation, new bone was formed at the edges of the blocks. After 12 weeks, new bone was observed in the central areas of the material. Notably, CO3 Ap blocks with pore sizes of 100-200 µm were the most effective, exhibiting approximately 23% new bone area. This study sheds new light on the fabrication of tailored porous blocks and provides a useful guide for designing artificial bones.
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Apatitas , Huesos , Animales , Apatitas/química , Fosfatos , Porosidad , ConejosRESUMEN
Surgical site infection (SSI) is a severe complication associated with orthopedic bone reconstruction. For both infection prevention and bone regeneration, the framework surface of osteoconductive and bioresorbable scaffolds must be locally modified by minimum antibacterial substances, without sacrificing the osteoconductivity of the scaffold framework. In this study, we fabricated antibacterial honeycomb scaffolds by replacing carbonate apatite, which is the main component of the scaffold, with silver phosphate locally on the scaffold surface via dissolution-precipitation reactions. When the silver content was 9.9 × 10-4 wt %, the honeycomb scaffolds showed antibacterial activity without cytotoxicity and allowed cell proliferation, differentiation, and mineralization. Furthermore, the antibacterial honeycomb scaffolds perfectly prevented bacterial infection in vivo in the presence of methicillin-resistant Staphylococcus aureus, formed new bone at 2 weeks after surgery, and were gradually replaced with a new bone. Thus, the antibacterial honeycomb scaffolds achieved both infection prevention and bone regeneration. In contrast, severe infection symptoms, including abscess formation, osteolytic lesions, and inflammation, occurred 2 weeks after surgery when honeycomb scaffolds without silver phosphate modification were implanted. Nevertheless, the unmodified honeycomb scaffolds eliminated bacteria and necrotic bone through their scaffold channels, resulting in symptom improvement and bone formation. These results suggest that the honeycomb structure is inherently effective in hindering bacterial growth. This novel insight may contribute to the development of antibacterial scaffolds. Moreover, our modification method is useful for providing antibacterial activity to various biomaterials.
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Antibacterianos/farmacología , Materiales Biocompatibles/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Antibacterianos/química , Materiales Biocompatibles/química , Regeneración Ósea/efectos de los fármacos , Ensayo de Materiales , Pruebas de Sensibilidad Microbiana , Andamios del Tejido/químicaRESUMEN
Fracture-related infections require both treatments for bacteria removal and bone reconstruction. The use of combined broad-spectrum antibacterial silver compounds and artificial bone with high osteogenic activity is considered to be an effective strategy for achieving these treatments in one surgery. However, silver compounds are toxic for living tissues even at low concentrations. Herein, we investigated the no-observed-effect level (NOEL) of silver phosphate (Ag3PO4) in a bone substitute composed of carbonate apatite (CO3Ap), a bone mineral, using in vitro and in vivo experiments. In vitro experiments demonstrated that the CO3Ap artificial bone containing ≥0.1 wt % Ag3PO4 exerted antibacterial effects against Staphylococcus epidermidis, while those containing ≤0.3 wt % Ag3PO4 did not affect cellular adhesion, proliferation, differentiation, and calcification of osteoblast-like MC3T3-E1 cells. In vivo experiments demonstrated that the CO3Ap artificial bone containing ≤0.3 wt % Ag3PO4 replaced a new bone to the same levels as those without Ag3PO4 4 weeks after implantation into the bone defect of the rabbit femur condyle. However, the CO3Ap artificial bone containing 0.3 wt % Ag3PO4 caused an inflammatory reaction, whereas those containing ≤0.1 wt % Ag3PO4 did not. Thus, both bone regeneration and infection control without any adverse effects were achieved using the CO3Ap artificial bone containing 0.1 wt % Ag3PO4, indicating that the NOEL of Ag3PO4 was 0.1 wt %. Our results provide an effective strategy for the treatments of fracture-related infections.
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Regeneración Ósea , Compuestos de Plata , Animales , Apatitas , Huesos , Nivel sin Efectos Adversos Observados , Fosfatos , ConejosRESUMEN
Octacalcium phosphate (OCP) has received considerable attention in the field of ceramic biomaterials as an advanced functional material. It exhibits a layered structure composed of apatitic and hydrated layers and can incorporate various dicarboxylate ions into the hydrated layer. Saturated dicarboxylic acids (HOOC(CH2)nCOOH) with an odd number of methylene groups (-CH2-) exhibit lower incorporation fractions than those with an even number of methylene groups, possibly owing to a compositional dependence on the synthetic method. In this study, calcium carbonate, phosphoric acid, and various amounts of glutaric acid were used to produce glutarate-ion-incorporated OCP by a wet chemical method, which is different from the conventional synthetic strategy. While utilising 1-20 mmol of glutaric acid during synthesis did not produce the desired product, using 25 mmol of glutaric acid resulted in the formation of single-phase glutarate-ion-incorporated OCP with a Ca/P molar ratio of 1.57 and a 90% incorporation fraction of glutarate ions. This glutarate-ion-incorporation fraction is significantly higher than that reported in the previous studies (35%). Thus, the synthetic procedure proposed herein was able to produce single-phase OCP containing glutarate ions with a high incorporation fraction. Our findings can contribute to development of novel functional ceramic biomaterials in the future.