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Carbonate apatite (CO 3 Ap)-granules bone substitute exhibits excellent osteoconductivity and replaced by a new bone based on bone remodeling process. However, no improvement has been made so far with respect to the drawbacks of granules; i.e., intraoperative scatter and postoperative migration. The aim of this study was to evaluate the feasibility of fabricating a CO 3 Ap-granules sponge to overcome these drawbacks. The CO 3 Ap granules sponge was successfully fabricated by mixing 300–600 µm CO 3 Ap granules with 3 % atelocollagen, followed by lyophilization at − 70 °C for 24 h and a dehydrothermal treatment at 150 °C for 24 h. The CO 3 Ap-granules sponge and CO 3 Ap-granules were implanted into rat calvarial bone defects for 2 and 4 weeks. No significant intraoperative scatter and postoperative migration were evident when the bone defects were reconstructed with the CO 3 Ap-granules sponge, whereas significant both intraoperative scatter and postoperative migration were observed when the bone defect was reconstructed with CO 3 Ap granules. Although less osteogenesis was anticipated for the CO 3 Ap-granules sponge due to the coverage of CO 3 Ap-granules surface with atelocollagen, no significant differences were observed in bone formation between the CO 3 Ap-granules sponge and CO 3 Ap-granules cases because the 3 % atelocollagen and lyophilization kept the CO 3 Ap granules surface only partially covered. Consequently, the CO 3 Ap-granules sponge and CO 3 Ap-granules exhibited similar bone formation at both 2 and 4 weeks after surgery. Thus, the CO 3 Ap-granules sponge improved the handling performance and retention ability at the bone defects without scarifying the osteogenesis of CO 3 Ap-granules. [ABSTRACT FROM AUTHOR]

Three-dimensional interconnected porous carbonate apatite (3D-CO 3 Ap) bone grafts facilitate rapid bone replacement because of their structure, which supports cellular infiltration. Existing 3D-CO 3 Ap grafts have demonstrated limited mechanical strength, with a maximum compressive strength of 3 MPa. By fusing polymer-bound CaCO 3 granules, followed by the debinding and compositional transformation of the granules via a dissolution–precipitation reaction, we successfully fabricated 3D-CO 3 Ap grafts that exhibited remarkably enhanced compressive strengths, which were recorded at 14.9 ± 3.7 MPa. The use of spherical granules, which provide more uniform and effective intergranular contacts than cylindrical granules, was key to achieving higher mechanical strength and superior bone formation. 3D-CO 3 Ap developed with spherical granules not only exhibited higher compressive strength, but also enhanced new bone formation compared with those fabricated with cylindrical granules. This study underscores the significance of porous microstructure design in 3D-CO 3 Ap, highlighting its critical role in optimizing both mechanical properties and bone regeneration capabilities. [ABSTRACT FROM AUTHOR]

Featured Application: This study provides an innovative approach to prevent the migration of carbonate apatite (CAp) granules during implantation. The proposed method combines the setting properties of calcium sulfate hemihydrate (CSH) with CAp granules, enabling their use as a stable, porous scaffold for bone regeneration. Granular bone substitutes are commonly used in dental treatments owing to their adaptability to irregular bone defects. However, granule migration during and after implantation poses a significant challenge, impairing bone regeneration. This study addresses this issue by setting carbonate apatite (CAp) granules using crystal interlocking owing to the bassanite (calcium sulfate hemihydrate (CSH))-to-gypsum (calcium sulfate dihydrate (CSD)) transformation on the granule surface. CAp granules were mixed with CSH slurry (water/CSH ratio of 0.4) at varying CSH/CAp ratios of 0.33, 0.43, 0.54, 0.67, and 0.82. At all of these mixing ratios, needle-shaped CSD crystals formed on the CAp granule surface, and the CSD crystals interlocked with each other; consequently, CAp granules were set. As the CSH/CAp ratio increased from 0.33 to 0.82, the CSD crystal length increased from 6.58 to 6.79 μm, while the setting time decreased from 30.3 to 15.5 min. Although the porosity of the set CAp granules decreased with an increase in the CSH/CAp ratio, the set granules maintained intergranular spaces of 77.3 μm at a CSH/CAp ratio of 0.82 conducive to cellular infiltration. After immersion in saline for six days, the set CAp granules at a CSH/CAp ratio of 0.82 maintained their original shape, demonstrating enhanced stability compared to lower CSH/CAp ratios where partial or complete collapse occurred. The porosity and specific surface area increased to 59.9% and 3.66 m2/g, respectively, and the intergranular spaces increased to 176.4 μm. Therefore, mixing the CAp granules with CSH at a ratio of 0.82 may prevent granule migration during and after implantation. Moreover, the CSD component of the granules is likely to resorb more rapidly than the CAp component in vivo, promoting porosity in the set granules and facilitating efficient bone replacement. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness of CO3Ap granules in the mandibular bone defects by using computed tomography (CT) images. Methods: This study was retrospective case series of mandibular bone defect reconstruction using CO3Ap granules. Six patients with jawbone cysts treated by simultaneous grafting CO3Ap granules after cyst enucleation were enrolled. Patients without grafting CO3Ap granules were excluded. Mandibular bone height including buccolingual bone height, the change of perpendicular distance between the buccolingual line to the alveolar ridge, and the three-dimensional volume of remaining CO3Ap granules were analyzed using CT images obtained at 3, 6, 12, 18, and 24 months postoperatively. Results: Postoperative CT images showed that cortical and cancellous bone-like structures were formed on the grafting area periphery and inside the defect, respectively, with gradual resorption of the CO3Ap granules. Furthermore, there was no evidence of leaving bone defect even at the center of the lesion when the defect was successfully reconstructed by filling it with CO3Ap granules. The percentage volume of remaining CO3Ap granules to the volume at 3 months postoperatively were 76.1 ± 13.1%, 35.8 ± 22.5%, 25.0 ± 13.0%, and 9.9 ± 6.4% at 6, 12, 18, and 24 months postoperatively, and the volume reduction rate increased significantly within 12 months postoperatively. Conclusion: Grafting CO3Ap granules after the enucleation of a jawbone cyst is a good reconstructive treatment option for postoperative prosthetic treatment because CO3Ap granules are gradually replaced by new bone while preserving the contour of the mandibular bone. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Abstract Bone graft granules are valuable tools for ridge area bone grafting owing to their ease of manipulation and interconnected porous structure. Guided bone regeneration (GBR) using barrier membranes is commonly used for alveolar ridge augmentation; however, the surgical procedures are technically complicated. In this study, we fabricated bioresorbable mesh domes (BMDs) using two types of Vicryl mesh (woven and knitted types) containing carbonate apatite granules. BMD samples were prepared in three groups: upper sides made from the woven type (UW) and lower sides made from the woven type (LW) (the UW/LW group), upper sides made from the woven type (UW) and lower sides made from the knitted type (LK) (the UW/LK group), and upper sides made from the knitted type (UK) and lower sides made from the knitted type (LK) (the UK/LK group). The samples were subsequently implanted into rabbit calvaria, and radiomorphometric and histological analyses were conducted. The UK/LK group exhibited enhanced appositional bone formation because the knitted mesh on the skin side prevented the infiltration of a substantial amount of fibrous tissue. This increase in bone formation could be attributed to the interaction between granules and osteoprogenitors that pass through the mesh from the host bone. Conversely, the UW/LW and UW/LK groups presented limited appositional bone formation. Compared with knitted mesh, woven mesh might tend to be absorbed over a short span, allowing fibrous tissue invasion and inhibiting new bone formation. Additionally, BMDs could retain granules in a targeted location and avoid displacement of the granules to unintended locations. Graphical Abstract

Bone graft granules are valuable tools for ridge area bone grafting owing to their ease of manipulation and interconnected porous structure. Guided bone regeneration (GBR) using barrier membranes is commonly used for alveolar ridge augmentation; however, the surgical procedures are technically complicated. In this study, we fabricated bioresorbable mesh domes (BMDs) using two types of Vicryl mesh (woven and knitted types) containing carbonate apatite granules. BMD samples were prepared in three groups: upper sides made from the woven type (UW) and lower sides made from the woven type (LW) (the UW/LW group), upper sides made from the woven type (UW) and lower sides made from the knitted type (LK) (the UW/LK group), and upper sides made from the knitted type (UK) and lower sides made from the knitted type (LK) (the UK/LK group). The samples were subsequently implanted into rabbit calvaria, and radiomorphometric and histological analyses were conducted. The UK/LK group exhibited enhanced appositional bone formation because the knitted mesh on the skin side prevented the infiltration of a substantial amount of fibrous tissue. This increase in bone formation could be attributed to the interaction between granules and osteoprogenitors that pass through the mesh from the host bone. Conversely, the UW/LW and UW/LK groups presented limited appositional bone formation. Compared with knitted mesh, woven mesh might tend to be absorbed over a short span, allowing fibrous tissue invasion and inhibiting new bone formation. Additionally, BMDs could retain granules in a targeted location and avoid displacement of the granules to unintended locations. [ABSTRACT FROM AUTHOR]

Mesoporous calcium phosphate based-bioceramics with ionic substitution have attracted attention for treatment of bone diseases and bone regeneration. Carbonate apatite (CO3Ap) is a promising candidate for bone replacement through bone remodelling, similar to that of autologous bone, owing to the chemical composition of the bone mineral. In this work, we present a dual approach to synthesize mesoporous carbonate apatite (CO3Ap) and strontium-substituted CO3Ap (Sr-CO3Ap) artificial bone nanocrystals, aiming to assess the impact of strontium on CO3Ap characteristics and biological performance. Mesoporous CO3Ap was created by transforming hard templates composed of CaCO3, while Sr-substituted CaCO3 (Sr-CaCO3) microspheres were formed using an organic complexing agent to induce pore formation. The resulting CO3Ap and Sr-CO3Ap granules exhibited an irregular shape, with rod-like nanocrystals composing their particles. Adsorption/desorption isotherms confirmed the mesoporous nature of the structures, featuring pore sizes ranging from 10 to 50 nm. Specifically, mesoporous CO3Ap displayed slit-like pores, while Sr-CO3Ap showed cylinder-like ones. High-resolution transmission electron microscopy images of Sr-CO3Ap powder revealed mesopores within the particles, with Sr-CO3Ap exhibiting larger pore volume and specific surface area compared to CO3Ap. When osteoblast-like MC3T3-E1 cells were cultured on both CO3Ap and Sr-CO3Ap samples, they demonstrated good cell attachment, proliferation rates, and increased ALP activity, particularly evident at higher strontium concentrations. These findings suggest promising potential for further exploration of mesoporous apatite nanocrystals in bone replacement and drug delivery applications. [ABSTRACT FROM AUTHOR]

Mohammad Borhan Uddin,1 Mark M Banaszak Holl,2,3 Ezharul Hoque Chowdhury4,5 1Department of Pharmaceutical Sciences, School of Health and Life Sciences, North South University, Dhaka, Bangladesh; 2Department of Mechanical and Materials Engineering, School of Engineering, University of Alabama at Birmingham, Birmingham, AL, USA; 3Division of Pulmonology, Allergy, and Critical Care Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; 4Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Subang Jaya, Selangor, 47500, Malaysia; 5Nanoflex LLC, Leesburg, FL, 34748, USACorrespondence: Ezharul Hoque Chowdhury, Tel +1 352 409 2283, Email chowdhury@nanoflex-usa.com; Mohammad Borhan Uddin, Tel +880-1974276229, Email mohammad.uddin@northsouth.eduIntroduction: Dysregulated calcium homeostasis and consequentially aberrant Ca2+ signalling could enhance survival, proliferation and metastasis in various cancers. Despite rapid development in exploring the ion channel functions in relation to cancer, most of the mechanisms accounting for the impact of ion channel modulators have yet to be fully clarified. Although harnessing small interfering RNA (siRNA) to specifically silence gene expression has the potential to be a pivotal approach, its success in therapeutic intervention is dependent on an efficient delivery system. Nanoparticles have the capacity to strongly bind siRNAs. They remain in the circulation and eventually deliver the siRNA payload to the target organ. Afterward, they interact with the cell surface and enter the cell via endocytosis. Finally, they help escape the endo-lysosomal degradation system prior to unload the siRNAs into cytosol. Carbonate apatite (CA) nanocrystals primarily is composed of Ca2+, carbonate and phosphate. CA possesses both anion and cation binding domains to target negatively charged siRNA molecules.Methods: Hybrid CA was synthesized by complexing CA NPs with a hydrophilic polysaccharide – hyaluronic acid (HA). The average diameter of the composite particles was determined using Zetasizer and FE-SEM and their zeta potential values were also measured.Results and Discussion: The stronger binding affinity and cellular uptake of a fluorescent siRNA were observed for HA-CA NPs as compared to plain CA NPs. Hybrid CA was electrostatically bound individually and combined with three different siRNAs to silence expression of calcium ion channel and transporter genes, TRPC6, TRPM8 and SLC41A1 in a human breast cancer cell line (MCF-7) and evaluate their potential for treating breast cancer. Hybrid NPs carrying TRPC6, TRPM8 and SLC41A1 siRNAs could significantly enhance cytotoxicity both in vitro and in vivo. The resultant composite CA influenced biodistribution of the delivered siRNA, facilitating reduced off target distribution and enhanced breast tumor targetability.Keywords: carbonate apatite, nanoparticles, siRNA, breast cancer, cytotoxicity, hyaluronic acid, calcium ion channel, transporter genes, TRPC6, TRPM8, SLC41A1

Introduction: For deep intrabony defects or Class II furcation involvements (FI), periodontal tissue regenerative therapy combined with bone graft materials and a barrier membrane is recommended. The objective of this study was to assess the safety and efficacy of using carbonate apatite (CO3Ap) granules and absorbable poly(lactic acid/caprolactone) (PLCL) membranes for periodontal regeneration in the treatment of intrabony defects and mandibular Class II FI. Methods: This prospective pilot clinical study, conducted at a single center with a single-arm design, aimed to assess the safety and efficacy of CO3Ap and PLCL membranes in patients with periodontitis. A total of 9 patients with 10 teeth, including seven deep intrabony defects and three Class II FI, were treated with CO3Ap granules and PLCL membranes. Clinical parameters such as probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BOP), tooth mobility (Mo), Plaque Index (PI), and Gingival Index (GI) were assessed at baseline, 6 and 12 months post-surgery. Radiographic analysis was performed using dental X-rays and cone beam computed tomography (CBCT) images taken at baseline, 6, and 12 months post-surgery. Results: Postoperative healing was uneventful in most of the cases. In some cases, membrane exposures were observed. However, there were no signs of inflammation, such as abnormal bleeding, pain, swelling, or pus. These exposures eventually healed well in the end. The mean reductions in PPD at 6 and 12 months were 4.5 ± 1.6 mm and 4.9 ± 1.4 mm, respectively, while the mean gains in CAL were 4.4 ± 1.7 mm at 6 months and 4.6 ± 1.2 mm at 12 months. Radiographic analysis showed improvements in linear bone height within intrabony defects and in the vertical subclassification of FI in Class II FI. Conclusions: Despite the limitations of this study, periodontal regenerative therapy using CO3Ap granules and a PLCL membrane demonstrated promising clinical safety and efficacy for treating intrabony defects and mandibular Class II furcation involvement.

Rapid bone regeneration is crucial for restoring alveolar bone and oral functions following periodontal diseases. However, the development of effective biomedical materials for this purpose remains insufficient. While bone autografts can enhance bone regeneration, they are invasive to healthy areas. Specifically, for alveolar bone regeneration, the implanted material must possess adequate mechanical strength. Moreover, local administration is preferred for older adults, who are a primary target population, to maintain their quality of life. We developed a silica-substituted carbonate apatite (CO3Ap–silica) block as newly bone substitute with a bone growth factor, featuring the major inorganic component of mature bone to enhance bone regeneration. CO3Ap–silica block stimulated the bone remodeling process at the implantation site and demonstrated significantly better bone regeneration compared to currently used carbonate apatite substitutes. Therefore, this new material is expected to advance technologies for restoring occlusal function after periodontal disease.

ObjectiveThis study aimed to histologically compare periodontal regeneration of one-wall intrabony defects treated with open flap debridement, β-tricalcium phosphate (β-TCP), and carbonate apatite (CO3Ap) in dogs.MethodsThe mandibular third premolars of four beagle dogs were extracted. Twelve weeks after the extraction, a one-wall bone defect of 4 mm × 5 mm (mesio-distal width × depth) was created on the distal side of the mandibular second premolar and mesial side of the fourth premolar. Each defect was randomly allocated to open flap debridement (control group), periodontal regeneration utilizing β-TCP, or CO3Ap. Eight weeks after the surgery, histologic and histometric analyses were performed.ResultsNo ankylosis, infection, or acute inflammation was observed at any of the experimental sites. Newly formed bone and cementum were observed in all experimental groups. The mineral apposition rate of the alveolar bone crest was higher in the CO3Ap group than in the control and β-TCP groups. The ratio of the new bone area was significantly higher in the CO3Ap group than in the control group (P

Background and objectives. Relapse is acknowledged as a substantial failure subsequent to orthodontic correction. Transforming growth factor-beta 1 (TGF-β1) modulates osteoblastogenesis and stimulates β-catenin signaling. The purpose of this investigation was to assess the impact of nanoemulsion carbonate apatite (CHA) -statin on TGF-β1 levels in rats undergoing relapse. Materials and methods. A total of forty-eight rats (n = 48) were allocated into four distinct groups: control, CHA, statin, and CHA-statin. To apply 30g of mesial traction for seven days, a closed-coil spring was extended from the first maxillary molar on the right maxilla to the incisor. Seven days passed throughout that CHA hydrogel, statin and CHA-statin nano emulsion were administered every three days. Debonding the appliances subsequently permitted relapse. TGF-β1 levels were measured utilizing an enzyme-linked immunosorbent assay (ELISA) on days 0, 1, 7, and 14 subsequent to debonding. An analysis was conducted on the collected data utilizing ANOVA and a Tukey's test (p <0.05). Results. On day seven of the relapse phase, the control group had the lowest average; the difference was significant (p <0.05), followed by Group CHA, Group St, and Group CHA-St. Average TGF-β1 levels between the groups did not differ statistically significantly (p >0.05) on days 0 and 1 of orthodontic relapse movement. Out of all the groups, the one that got CHA-statin nanoemulsion had the highest mean values. Significant mean differences (p <0.05) from the highest average of group CHA-St, group CHA, group St, and the control group were found on day 14. Conclusions. The findings suggested nanoemulsion CHA-statin may raise TGF-β1 levels during orthodontic relapse. [ABSTRACT FROM AUTHOR]

The failure rate of calcium hydroxide [Ca(OH)2] as a pulp protection material is 13.64% one year after treatment. Carbonate apatite (CO3Ap) is a biocompatible material that has the ability to carry and release drugs in a phosphate-buffered saline (PBS) solution that functions to regulate the pH and osmolarity balance of cells. Ellagic acid (EA) is a natural, bioactive phenolic and flavonoid compound. 12.5% EA has been shown to inhibit the growth of Enterococcus faecalis. This research not only aims to develop a formula for Ca(OH)2 combined with CO3Ap, and ellagic acid (EA) solvent, but also investigates their effect on the cytotoxicity and proliferation of fibroblasts. Material samples were prepared by mixing various proportions of Ca(OH)2 with CO3Ap dissolved in 12.5% EA solvent. Baby hamster kidney-21 cells were prepared and incubated in a 96-well microplate for 24 h and 72 h with media containing the material samples. Cell viability was monitored by measuring the absorbance of each microplate using an ELISA reader. After 24 h, group 3 (50% CO3Ap wt%) showed the highest percentage of viable cells; after 72 h, the highest percentage was found in group 3 (50% CO3Ap wt%). Group 5 (87.5% CO3Ap) had the lowest percentage value of living cells after 24 and 72 h treatment. The difference between groups 3 and 5 at 24 hours was significant (p<0.05). The combinations in groups 1, 2, 3, and 4 were nontoxic and able to stimulate the proliferation of fibroblast cells and thus have ideal characteristics as a new candidate material for pulp capping. [ABSTRACT FROM AUTHOR]

Bladder lithiasis is common in developing countries. It has become rare in industrialized countries and exceptional in the absence of associated lower tract pathology. usually caused by urinary tract infections, urethral obstruction or the presence of intravesical foreign bodies. Open cystolithotomy was performed on a 45-year-old patient with lower abdominal pain, moderate dysuria, pollakiuria, nocturia, and hematuria for a long time. A stone of 12 × 8cm in size and approximately 620 grams in weight was removed. The cystoscopy was performed without any infravesical obstruction during the operation. The stone analysis showed 21% struvite and 79% carbonate apatite. Bladder lithiasis is common in Morocco. However, giant lithiasis is rare and is the consequence of neglected voiding disorders. Open cystolithotomy remains the most treatment in the management of giant stones.

Introduction: This study was designed to determine the mineral composition of calculi in nephrocalcinosis with nephrolithiasis, diagnose the underlying disease, and monitor the course of renal function in patients with nephrocalcinosis-nephrolithiasis. Methods: Renal calculi extruded in a series of 8 patients with nephrocalcinosis were analysed using Fourier transmission infrared spectrometry. In 4 patients, next-generation sequencing using a nephrocalcinosis-nephrolithiasis panel was performed to determine the nature of the underlying disease. In addition, longitudinal analysis of renal function was performed in all patients. Results: Seven patients revealed carbonate apatite as the sole constituent of renal calculi. One patient showed a mixed composition of dicalcium phosphate dihydrate/carbonate apatite at first analysis yet in subsequent episodes also had calculi composed of pure carbonate apatite. Further molecular analysis displayed distal renal tubular acidosis in 2 of 4 patients who consented to sequencing. No known genetic defect could be found in the other two cases. In line with prior reports, decline of renal function was dependent on underlying disease. Distal renal tubular acidosis revealed a progressive course of renal failure, whereas other causes showed stable renal function in long term analysis. Conclusion: Nephrocalcinosis with nephrolithiasis is a rare condition with heterogeneous aetiology. Yet mineral composition of renal calculi predominantly consisted of pure carbonate apatite. This uniform finding is similar to subcutaneous calcifications of various origins and might propose a general principle of tissue calcification. Progressive decline of renal function was found in distal renal tubular acidosis, whereas other conditions remained stable over time.

Granular bone substitutes are commonly used in dental treatments owing to their adaptability to irregular bone defects. However, granule migration during and after implantation poses a significant challenge, impairing bone regeneration. This study addresses this issue by setting carbonate apatite (CAp) granules using crystal interlocking owing to the bassanite (calcium sulfate hemihydrate (CSH))-to-gypsum (calcium sulfate dihydrate (CSD)) transformation on the granule surface. CAp granules were mixed with CSH slurry (water/CSH ratio of 0.4) at varying CSH/CAp ratios of 0.33, 0.43, 0.54, 0.67, and 0.82. At all of these mixing ratios, needle-shaped CSD crystals formed on the CAp granule surface, and the CSD crystals interlocked with each other; consequently, CAp granules were set. As the CSH/CAp ratio increased from 0.33 to 0.82, the CSD crystal length increased from 6.58 to 6.79 μm, while the setting time decreased from 30.3 to 15.5 min. Although the porosity of the set CAp granules decreased with an increase in the CSH/CAp ratio, the set granules maintained intergranular spaces of 77.3 μm at a CSH/CAp ratio of 0.82 conducive to cellular infiltration. After immersion in saline for six days, the set CAp granules at a CSH/CAp ratio of 0.82 maintained their original shape, demonstrating enhanced stability compared to lower CSH/CAp ratios where partial or complete collapse occurred. The porosity and specific surface area increased to 59.9% and 3.66 m2/g, respectively, and the intergranular spaces increased to 176.4 μm. Therefore, mixing the CAp granules with CSH at a ratio of 0.82 may prevent granule migration during and after implantation. Moreover, the CSD component of the granules is likely to resorb more rapidly than the CAp component in vivo, promoting porosity in the set granules and facilitating efficient bone replacement.

Among the various bone substitutes, carbonate apatite (CO3Ap) has received significant attention in the field of hard tissue regeneration due to its similarity in chemical composition to natural bone and its osteoconductivity and bioresorbability. This study aimed to develop a cost-effective method for fabricating porous CO3Ap blocks while maintaining a balance between porosity and mechanical properties. The level of interconnectivity in the porous structure was achieved by adjusting the pore volume fractions of the starting materials. The phase and microstructure characteristics of the porous CO3Ap blocks were assessed using techniques such as X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The diametral tensile strength (DTS) of the blocks was determined using a universal testing machine. The results demonstrated that the mechanical strength of the blocks stayed within a range that was suitable for handling properties. This advantage allows the porous blocks to withstand initial stress during implantation procedures or in the early stages of defect healing. [ABSTRACT FROM AUTHOR]

The newly developed mineral carbonated apatite has recently been proposed as a bone graft material for bone regenerative treatment in implant therapy. This case series details the clinical and radiographic outcomes of ridge preservation and ridge augmentation using only carbonated apatite as bone graft material for implant treatment. Twenty patients (36 sites) who required bone regeneration and implant placement were retrospectively assessed. Simultaneous carbonated apatite implant placement was performed using the simultaneous ridge preservation or augmentation approach on 24 sites in 13 patients with sufficient bone quantity for primary stabilization based on preoperative evaluation results. A staged ridge preservation or augmentation approach was used for the remaining 12 sites in seven patients with insufficient bone quantity. The mean regenerated bone height for each treatment method was as follows: simultaneous preservation, 7.4 ± 3.3 mm; simultaneous augmentation, 3.6 ± 2.3 mm; staged preservation, 7.2 ± 4.5 mm; and staged augmentation, 6.1 ± 2.7 mm. The mean regenerated bone width for each treatment method was as follows: simultaneous preservation, 6.5 ± 2.9 mm; simultaneous augmentation, 3.3 ± 2.5 mm; staged preservation, 5.5 ± 1.7 mm; and staged augmentation, 3.5 ± 1.9 mm. Ultimately, the use of carbonated apatite alone as a bone graft material in implant therapy resulted in stable and favorable bone regeneration. [ABSTRACT FROM AUTHOR]

Carbonate apatite (CAp) coating has been developed as a bioabsorbable corrosion-control coating for biodegradable Mg alloys. Carbonate content in the CAp coatings can be utilized to control the bioabsorbability and corrosion rate of CAp-coated Mg alloys. In this study, the carbonate content in the CAp coatings of pure Mg was varied by NaHCO 3 concentration of the coating solution from 0.25 to 1.0 mol/L, and hydroxyapatite (HAp) was formed without NaHCO 3. The CAp and HAp coatings were characterized using X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). The carbonate content in the apatite coatings formed with 0, 0.25, 0.5 and 1.0 mol/L NaHCO 3 was determined to be 2, 12, 15 and 18 wt%, respectively, from the apatite 002 plane XRD peak position using the existing conversion constant as well as from the coating composition obtained by the XPS analysis. The values of carbonate content obtained by each method were in good accordance, indicating that the carbonate content can be determined simply by XRD measurements. Two types of carbonate group were present in the CAp coatings, CO 3 2− and HCO 3 -, and the relative content of HCO 3 - to CO 3 2− increased with an increase in the carbonate content. [Display omitted] • Variation of carbonate content of CAp coatings of pure Mg with NaHCO 3 concentrations. • Accordance in carbonate content derived from XRD peak position and XPS quantification. • Simple determination of carbon content of CAp coatings by XRD is possible. • Two types of carbonate group in CAp coatings, CO 3 2− and HCO 3 -. [ABSTRACT FROM AUTHOR]

Bone defects represent an everyday challenge for clinicians who work in the fields of orthopedic surgery, maxillofacial and oral surgery, otorhinolaryngology, and dental implantology. Various bone substitutes have been developed and utilized, according to the needs of bone reconstructive surgery. Carbonate apatite has gained popularity in recent years, due to its excellent tissue behavior and osteoconductive potential. This systematic review aims to evaluate the role of carbonate apatite in bone reconstructive surgery and tissue engineering, analyze its advantages and limitations, and suggest further directions for research and development. The Web of Science, PubMed, and Scopus electronic databases were searched for relevant review articles, published from January 2014 to 21 July 2023. The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eighteen studies were included in the present review. The biological properties and medical applications of carbonate apatite (CO3Ap) are discussed and evaluated. The majority of articles demonstrated that CO3Ap has excellent biocompatibility, resorbability, and osteoconductivity. Furthermore, it resembles bone tissue and causes minimal immunological reactions. Therefore, it may be successfully utilized in various medical applications, such as bone substitution, scaffolding, implant coating, drug delivery, and tissue engineering. [ABSTRACT FROM AUTHOR]

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.

Introduction: This study was designed to determine the mineral composition of calculi in nephrocalcinosis with nephrolithiasis, diagnose the underlying disease, and monitor the course of renal function in patients with nephrocalcinosis-nephrolithiasis. Methods: Renal calculi extruded in a series of 8 patients with nephrocalcinosis were analysed using Fourier transmission infrared spectrometry. In 4 patients, next-generation sequencing using a nephrocalcinosis-nephrolithiasis panel was performed to determine the nature of the underlying disease. In addition, longitudinal analysis of renal function was performed in all patients. Results: Seven patients revealed carbonate apatite as the sole constituent of renal calculi. One patient showed a mixed composition of dicalcium phosphate dihydrate/carbonate apatite at first analysis yet in subsequent episodes also had calculi composed of pure carbonate apatite. Further molecular analysis displayed distal renal tubular acidosis in 2 of 4 patients who consented to sequencing. No known genetic defect could be found in the other two cases. In line with prior reports, decline of renal function was dependent on underlying disease. Distal renal tubular acidosis revealed a progressive course of renal failure, whereas other causes showed stable renal function in long term analysis. Conclusion: Nephrocalcinosis with nephrolithiasis is a rare condition with heterogeneous aetiology. Yet mineral composition of renal calculi predominantly consisted of pure carbonate apatite. This uniform finding is similar to subcutaneous calcifications of various origins and might propose a general principle of tissue calcification. Progressive decline of renal function was found in distal renal tubular acidosis, whereas other conditions remained stable over time. Plain Language Summary: Renal stones may occur in conditions that involve calcification of the kidney itself. In this case series, we chemically analysed these stones. In some cases, we also performed genetic tests. Interestingly, we found a similar composition in most stones, irrespective of the underlying disorder. This suggests a common mechanism of calcification. [ABSTRACT FROM AUTHOR]

Scaffolds having appropriate mechanical strength and providing a proper microenvironment for osteogenesis are expected to be effective alternatives to autografts for bone regeneration. In this study, ant‐nest type porous (ANP) scaffolds consisting of CO3Ap were fabricated using calcium carbonate powder or slurry and two types of polyurethane foam through a dissolution–precipitation reaction. ANP‐type, three‐dimensional, interconnected porous CO3Ap scaffolds were fabricated by burning out the struts of polyurethane foams embedded in CaCO3, followed by compositional transformation from CaCO3 to CO3Ap. The types of polyurethane foam and impregnation methods of CaCO3 into polyurethane form affected the geometry of the resulting ANP structures. Mechanical and in vivo biological performances of these scaffolds relied on the geometry of the ANP structures. The ANP structures displayed had a clear structural advantage in bone regeneration, owing to the promotion of cell and tissue migration throughout the scaffolds. In particular, ANP‐structured scaffolds, which had highest porosity, interconnectivity, and smallest strut thickness, had a mechanical strength comparable to cancellous bone, formed more new bone, were highly resorbed, resulting in cancellous bone‐like bone tissue regeneration at 12 weeks of healing. The results suggest that bone regeneration after the migration of cell and tissue into the entire scaffolds is affected by strut thickness preferentially over porosity and interconnectivity. ANP‐structured CO3Ap scaffolds are attractive for bone regeneration. [ABSTRACT FROM AUTHOR]

Autologous bone grafting is the primary method for treating alveolar clefts. However, bone grafting materials are desired as alternatives to autogenous bone to reduce surgical invasiveness. Here, we present an animal study evaluating the effect of carbonate apatite (CA) on the spontaneous eruption of permanent teeth. The bone grafting materials included CA, natural bovine bone (BB), and hydroxyapatite (HA). In 15 8-week-old male beagle dogs, the left mandibular deciduous premolars (DP) two and three were extracted and subsequently filled with CA, BB, and HA. The animals were euthanized after a predetermined number of days, and samples were collected for microcomputed tomography and histological evaluation. Spontaneous eruption of the succeeding permanent teeth (P3 and P4) was observed in the CA group at 14 weeks. Delayed eruption of the succeeding permanent teeth was observed in the BB and HA groups. CA could serve as a viable alternative to autogenous bone for treating alveolar clefts. [ABSTRACT FROM AUTHOR]

This study radiologically and histologically compared two bioresorbable bone substitutes with different compositions carbonate apatite (Cytrans® Granules; CGs) and ß-tricalcium phosphate (ß-TCP) for vertical bone augmentation on a rat skull using a polytetrafluoroethylene (PTFE) tubes. This PTFE tube was placed at the center of the skull, fixed with Super Bond, and augmented with CGs or ß-TCP granules. Specimens with surrounding tissue were harvested at 4, 8, and 12 weeks postoperatively, and radiological and histological evaluations were performed. The bone volume to total volume ratio (BV/TV) of the ß-TCP-implanted group was markedly higher than that of the CG-implanted group at 4 and 12 weeks postoperatively. Compared to CGs, ß-TCP exhibited the ability to form blood vessels into the graft material for a short period after transplantation, as well as an elevated production of collagen into ß-TCP granules during the bone formation process. [ABSTRACT FROM AUTHOR]

The rate of resorption of calcium phosphate self-hardening materials for bone regeneration can be changed by changing the phase composition. The Ca3(PO4)2/CaCO3/Ca(H2PO4)2·H2O/Na2HPO4·12H2O system is important for the synthesis of self-curing bioactive materials with variable resorption rates by changing the ratios of the initial components. Cement compositions in twelve figurative points of a four-component composition diagram at a fixed content in the α-Ca3(PO4)2 system were studied with XRD, FTIR, SEM, calorimetric, and volumetric methods to obtain an idea of the effect of composition on solubility in vitro and resorption in vivo. It was found that the presence of the highly resorbable phase of dicalcium phosphate dihydrate in cement and the substitution of phosphate ions with the carbonate ions of hydroxyapatite increased solubility in vitro and resorption in vivo. The obtained results confirm the possibility of changing the solubility of a final product in the Ca3(PO4)2/CaCO3/Ca(H2PO4)2·H2O/Na2HPO4·12H2O system by changing the ratio of the initial components.

Maxillary sinus augmentation with a lateral approach (MSA) is a well-established treatment. In this prospective study, we evaluated risk factors for postoperative bone graft displacement and reported the clinical application of long-term resorbable L-lactic acid/-caprolactone (PLA/PCL) as a barrier membrane to cover the open window in the lateral wall in MSA. Twenty-four patients underwent MSA according to the relevant criteria; CT data obtained before and 1 week (1 w) and 5–6 months (5 m) post-MSA, bone height changes, bone height reduction rates at 1 w and 5 m post-MSA, bone graft displacement measurements, and risk factors were examined. All patients showed bone height increments (p < 0.005). However, no difference was observed between 1 w and 5 m post-MSA. Bone graft displacement was observed in eight patients; the reduction rate from 1 w to 5 m post-MSA was 8.38% ± 4.88%. Sex, septa, maxillary sinus floor–palatal bone distance, and maxillary sinus floor–maxillary ostium distance were associated with bone graft displacement (p < 0.05). The height from the maxillary sinus floor to the palatal bone and the sinus angle influenced the augmentation degree (p < 0.05). The PLA/PCL membrane is compared favorably with other membranes and may be useful as a barrier membrane for the MSA open window. [ABSTRACT FROM AUTHOR]

Carbonate apatite (CA) is a synthetic derivative of hydroxyapatite, which we have been exploring as a drug delivery nanocarrier in the context of cancer in vitro and in vivo. This nanocarrier showed great potential delivering anti-cancer drugs, plasmids containing tumour suppressor genes and siRNAs against oncogenes in pre-clinical models. We compared here two formulations of CA—the low-Ca2+ CA (made with 4 mM Ca2+) used for in vitro studies in cell lines and the high-Ca2+ CA (made with 40 mM Ca2+) used in mouse models—in terms of protein corona formed with different concentrations of serum in vivo and in vitro. The 10-fold more Ca2+ in high-Ca2+ CA helped produce enough particles in an injectable volume for in vivo delivery of therapeutics. Both formulations made particles of similar size, but their composition differed slightly in terms of Na and Mg content. In serum-containing media, the size of the particles was dependent on the serum concentration. The protein corona around both formulations was almost similar and included albumin, fetuin, haemoglobin, and immunoglobulins. CA was not cytotoxic, and instead an increased expression of ribosomal machinery and glycolytic and cytoskeletal proteins was observed, which promoted translation, growth, and proliferation in cancer cells. [ABSTRACT FROM AUTHOR]

In the field of restorative dentistry, composite resin is quickly overtaking other materials in terms of usage. It resolves the issue of the toxic nature brought on by the amalgams’ mercury content. The mechanical properties of resin-based dental restorative composites can be enhanced with the addition of filler material. This study examines the effects of chitosan addition to dental composites with alumina, zirconia, and carbonate apatite nanoparticles on their characterization and hardness. The composite for direct restoration is prepared by mixing UDMA–TEGDMA–DMAEMA– HEMA as the matrix and alumina–zirconia–carbonate apatite as the filler in the presence of chitosan as a coupling agent. The weight ratio of filler to matrix used is 70:30. The effects of various concentrations of chitosan are varied at 2%, 4%, and 6%. Samples are prepared by a synthetizing process to obtain alumina–zirconia–carbonate apatite nanoparticles. The diffractogram from XRD shows the formation of t-ZrO2 and dahllite. SEM images reveals that the particle sizes of each sample with chitosan at 2%, 4%, and 6% are of 87.5 nm, 112.5 nm, and 150 nm, respectively. The hardness values of each sample with the same chitosan concentration are of 51.3 VHN, 28.24 VHN, and 25.48 VHN, respectively. Dental composites with less chitosan concentration promote a smaller size of alumina– zirconia–carbonate apatite nanoparticles and higher mechanical properties in dental restorative composites. [ABSTRACT FROM AUTHOR]

Biodegradable guided bone regeneration (GBR) membranes consist primarily of collagen and aliphatic polyesters. This study assessed the comparative efficacy of a poly(l-lactic-caprolactone) [P(LA/CL)] membrane versus that of a collagen membrane in GBR. Patients requiring GBR simultaneously or before dental implant placement in edentulous regions were randomly assigned to one of two membranes. Within each membrane, they were subdivided into 3 groups: dental implants were placed simultaneously with GBR in groups A and B, and 180 days post-GBR in group C. The augmented bone width was measured at 1, 3, and 6 mm from the implant's neck (groups A and B) or the reference line (group C), utilizing cone-beam computed tomography images, immediately and 150 days post-surgery. A histological study was performed to evaluate bone formation in group C. No adverse events were observed. In the collagen group, the absorbed ratios of the augmented bone were 40.9 ± 36.7%, 29.4 ± 30.1%, and 11.1 ± 22.0% at 1, 3, and 6 mm, respectively; the ratio at 6 mm was significantly lower than that at 1 mm (p = 0.0442). In the P(LA/CL) group, those were 26.2 ± 27.3%, 17.1 ± 19.7%, and 13.3 ± 16.4% at 1, 3, and 6 mm, respectively, with no significant difference at each point. No significant inter-membrane differences were observed. The bone augmentation potential of the P(LA/CL) membrane matched that of the collagen membrane. P(LA/CL) could be used as a safe and effective membrane in GBR. [ABSTRACT FROM AUTHOR]

Aim: This study histologically compared two bioresorbable bone substitutes with different composition, carbonate apatite (CO3Ap) and beta‐tricalcium phosphate (β‐TCP), through alveolar bone augmentation with simultaneous titanium implant placement in beagle dogs. Methods: Bone defects (length 7 mm, width 2 mm, and depth 6 mm) were created bilaterally at mandibular premolar sites and augmented with either CO3Ap or β‐TCP granules after titanium implant installation. The specimens with the surrounding tissue were harvested from the mandible at 4, 12, and 24 weeks postoperatively, and histological evaluation was performed. Results: Most β‐TCP granules dissolved in early stages postoperatively, resulting in a lower volume of alveolar bone surrounding the titanium implant. By contrast, in the case of CO3Ap group, the alveolar ridge was reconstructed without reducing the alveolar bone height, and almost all implant threads were covered with new bone by at least 12 weeks postoperatively. Quantitatively, the CO3Ap group showed a significantly higher percentage of new bone formation in the alveolar ridge portion at all follow‐ups. Additionally, it demonstrated a significantly higher bone‐to‐implant contact ratio than that of the β‐TCP group at 12 and 24 weeks after implantation (70.8 ± 5.6% vs. 29.3 ± 16.4% and 54.8 ± 6.9% vs. 41.8 ± 2.2%, respectively). Conclusion: In conclusion, based on the superior outcomes noted in this study, CO3Ap is useful for clinical use in alveolar bone augmentation with simultaneous implant placement. [ABSTRACT FROM AUTHOR]

Metal materials used as bone implants are not new today. In fact, almost 70% of implant materials are made of metal. Magnesium biocomposites with Carbonate Apatite or Hydroxyapatite reinforcements have promising potential as implants, one of the properties of these composites is biocompatible and bioactive to accelerate bone growth. There have been many studies on the development of Mg-CAp and Mg-HAp as biocomposite implant materials. Various methods of making these biocomposites have been carried out, such as sintering, microwave, coating, casting, and extrusion. From the fabrication process, observations were made regarding mechanical properties and chemical structure. The results show that CAp and HAp can suppress the corrosion rate of Magnesium, which is one of the weak properties that must be improved. Then it can increase the biological activity of Mg composites and has the ability of bone induction and bone conduction. In addition, the mechanical properties have increased in tensile, compression, and microhardness testing. However, so far, the research on Mg-HAp and Mg-CAp has only been limited to animal testing and has not been applied to humans. So, the potential for development and research is still open actually to be implemented in the orthopedic field. [ABSTRACT FROM AUTHOR]

The rate of resorption of calcium phosphate self-hardening materials for bone regeneration can be changed by changing the phase composition. The Ca3(PO4)2/CaCO3/Ca(H2PO4)2·H2O/Na2HPO4·12H2O system is important for the synthesis of self-curing bioactive materials with variable resorption rates by changing the ratios of the initial components. Cement compositions in twelve figurative points of a four-component composition diagram at a fixed content in the α-Ca3(PO4)2 system were studied with XRD, FTIR, SEM, calorimetric, and volumetric methods to obtain an idea of the effect of composition on solubility in vitro and resorption in vivo. It was found that the presence of the highly resorbable phase of dicalcium phosphate dihydrate in cement and the substitution of phosphate ions with the carbonate ions of hydroxyapatite increased solubility in vitro and resorption in vivo. The obtained results confirm the possibility of changing the solubility of a final product in the Ca3(PO4)2/CaCO3/Ca(H2PO4)2·H2O/Na2HPO4·12H2O system by changing the ratio of the initial components. [ABSTRACT FROM AUTHOR]

Bioactive glasses are considered biocompatible materials that form a hydroxyapatite-like layer on the surface that allows strong adhesion to soft and hard tissues. This study aims to develop a method to fabricate a borate silicate ceramic biomaterial with a chemical composition of Ca 11 Si 4 B 2 O 22 using sodium metaborate (NaBO 2) as a flux. X-ray diffraction (XRD), scanning electron microscopy energy distribution spectrometer (SEM-EDS), and Fourier transform infrared spectrometer (FTIR) were used to analyze the structure, surface composition and chemical bonding of the bioactive borate silicate. In addition, the pH measurements and biodegradability behavior of the fabricated glass structures were investigated after immersion in simulated body fluid for 2, 7, 14, and 21 days, respectively. The results showed that the glass-ceramic structure, which was transferred from the crystalline phase Ca 11 Si 4 B 2 O 22 to a hydroxyapatite phase after incubation, started on the second day. In addition, the formed hydroxyapatite crystals developed due to the prolonged immersion time, reflecting biodegradable behavior. The antimicrobial activity of the prepared ceramic showed high inhibitory activity against Enterococcus faecalis and Streptococcus mutans. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to histologically compare periodontal regeneration of one-wall intrabony defects treated with open flap debridement, β-tricalcium phosphate (β-TCP), and carbonate apatite (CO3Ap) in dogs. Methods: The mandibular third premolars of four beagle dogs were extracted. Twelve weeks after the extraction, a one-wall bone defect of 4 mm × 5 mm (mesio-distal width × depth) was created on the distal side of the mandibular second premolar and mesial side of the fourth premolar. Each defect was randomly allocated to open flap debridement (control group), periodontal regeneration utilizing β-TCP, or CO3Ap. Eight weeks after the surgery, histologic and histometric analyses were performed. Results: No ankylosis, infection, or acute inflammation was observed at any of the experimental sites. Newly formed bone and cementum were observed in all experimental groups. The mineral apposition rate of the alveolar bone crest was higher in the CO3Ap group than in the control and β-TCP groups. The ratio of the new bone area was significantly higher in the CO3Ap group than in the control group (P

Abstract Carbonate apatite (CO3Ap) granules are useful as a bone substitute because they can be remodeled to new natural bone in a manner that conforms to the bone remodeling process. However, reconstructing large bone defects using CO3Ap granules is difficult because of their granular shape. Therefore, we fabricated CO3Ap honeycomb blocks (HCBs) with continuous unidirectional pores. We aimed to elucidate the tissue response and availability of CO3Ap HCBs in the reconstruction of rabbit mandibular bone defects after marginal mandibulectomy. The percentages of the remaining CO3Ap area and calcified bone area (newly formed bone) were estimated from the histological images. CO3Ap area was 49.1 ± 4.9%, 30.3 ± 3.5%, and 25.5 ± 8.8%, whereas newly formed bone area was 3.0 ± 0.6%, 24.3 ± 3.3%, and 34.7 ± 4.8% at 4, 8, and 12 weeks, respectively, after implantation. Thus, CO3Ap HCBs were gradually resorbed and replaced by new bone. The newly formed bone penetrated most of the pores in the CO3Ap HCBs at 12 weeks after implantation. By contrast, the granulation tissue scarcely invaded the CO3Ap HCBs. Some osteoclasts invaded the wall of CO3Ap HCBs, making resorption pits. Furthermore, many osteoblasts were found on the newly formed bone, indicating ongoing bone remodeling. Blood vessels were also formed inside most of the pores in the CO3Ap HCBs. These findings suggest that CO3Ap HCBs have good osteoconductivity and can be used for the reconstruction of large mandibular bone defects. Graphical Abstract The CO3Ap HCB were gradually resorbed and replaced by newly formed bone.

The environment model is used to describe the location of carbonate in nine carbonated apatites containing varied percentages of carbonate and Na+, K+, or NH4+ ions. Unlike the traditional model for carbonate substitution, which identifies different locations and orientations of the carbonate ion in the apatite structure, the environment model utilizes the different structural surroundings to describe the different types of carbonate. The A-type carbonate environment is assigned to channels lined only with calcium ions (A-channel configuration = Ca6) or to channels containing one Na+ or a vacancy (A′-channel configuration = Ca5Na or Ca5▢), and the B-type carbonate environment is the surroundings of the replaced phosphate ion. The assignments are made by peak-fitting the carbonate asymmetric stretch region (ν3) of the IR spectrum, following previously published criteria. These assignments lead to the conclusion that the percentage of channel carbonate (A- and A′-environments) is greater than that of B-type for each of these carbonated apatites. In general, the use of triammonium phosphate as the phosphate source in the synthesis produces apatites with larger amounts of channel carbonate (A- and A′-environments), while the use of sodium-containing phosphate reagents produces smaller amounts of channel carbonate. The environment model provides explanations for the differences within IR and NMR spectra obtained for apatites containing a range of total carbonate content. The B-type appearance of the carbonate ν3 region of the IR spectrum is found primarily in apatites containing sodium, which allows increased amounts of carbonation via co-substitution of Na+ with carbonate and creation of A′-environments with populations equal to that of B-type carbonate. The presence of ammonium or alkali metal salts with cations larger than Na+ results in the utilization of a charge-balance mechanism that produces vacancies rather than cation substitution in the channel. The carbonated apatites formed with primary utilization of the vacancy mechanism generally contain greater percentages of carbonate in the A-environment and carbonate IR spectra that contain an obvious high-frequency peak at about 1550 cm–1. The multiple peaks in the solid state 13C NMR spectra previously observed for carbonated apatite are attributed to substitution in the A-, A′-, and B-environments rather than different stereo-chemical orientations of the carbonate ion. [ABSTRACT FROM AUTHOR]

Bone defects represent an everyday challenge for clinicians who work in the fields of orthopedic surgery, maxillofacial and oral surgery, otorhinolaryngology, and dental implantology. Various bone substitutes have been developed and utilized, according to the needs of bone reconstructive surgery. Carbonate apatite has gained popularity in recent years, due to its excellent tissue behavior and osteoconductive potential. This systematic review aims to evaluate the role of carbonate apatite in bone reconstructive surgery and tissue engineering, analyze its advantages and limitations, and suggest further directions for research and development. The Web of Science, PubMed, and Scopus electronic databases were searched for relevant review articles, published from January 2014 to 21 July 2023. The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eighteen studies were included in the present review. The biological properties and medical applications of carbonate apatite (CO3Ap) are discussed and evaluated. The majority of articles demonstrated that CO3Ap has excellent biocompatibility, resorbability, and osteoconductivity. Furthermore, it resembles bone tissue and causes minimal immunological reactions. Therefore, it may be successfully utilized in various medical applications, such as bone substitution, scaffolding, implant coating, drug delivery, and tissue engineering.

The newly developed mineral carbonated apatite has recently been proposed as a bone graft material for bone regenerative treatment in implant therapy. This case series details the clinical and radiographic outcomes of ridge preservation and ridge augmentation using only carbonated apatite as bone graft material for implant treatment. Twenty patients (36 sites) who required bone regeneration and implant placement were retrospectively assessed. Simultaneous carbonated apatite implant placement was performed using the simultaneous ridge preservation or augmentation approach on 24 sites in 13 patients with sufficient bone quantity for primary stabilization based on preoperative evaluation results. A staged ridge preservation or augmentation approach was used for the remaining 12 sites in seven patients with insufficient bone quantity. The mean regenerated bone height for each treatment method was as follows: simultaneous preservation, 7.4 ± 3.3 mm; simultaneous augmentation, 3.6 ± 2.3 mm; staged preservation, 7.2 ± 4.5 mm; and staged augmentation, 6.1 ± 2.7 mm. The mean regenerated bone width for each treatment method was as follows: simultaneous preservation, 6.5 ± 2.9 mm; simultaneous augmentation, 3.3 ± 2.5 mm; staged preservation, 5.5 ± 1.7 mm; and staged augmentation, 3.5 ± 1.9 mm. Ultimately, the use of carbonated apatite alone as a bone graft material in implant therapy resulted in stable and favorable bone regeneration.

Carbonate apatite (CO3Ap) is a bioceramic material with excellent properties for bone and dentin regeneration. To enhance its mechanical strength and bioactivity, silica calcium phosphate composites (Si-CaP) and calcium hydroxide (Ca(OH)2) were added to CO3Ap cement. The aim of this study was to investigate the effect of Si-CaP and Ca(OH)2 on the mechanical properties in terms of the compressive strength and biological characteristics of CO3Ap cement, specifically the formation of an apatite layer and the exchange of Ca, P, and Si elements. Five groups were prepared by mixing CO3Ap powder consisting of dicalcium phosphate anhydrous and vaterite powder added by varying ratios of Si-CaP and Ca(OH)2 and 0.2 mol/L Na2HPO4 as a liquid. All groups underwent compressive strength testing, and the group with the highest strength was evaluated for bioactivity by soaking it in simulated body fluid (SBF) for one, seven, 14, and 21 days. The group that added 3% Si-CaP and 7% Ca(OH)2 had the highest compressive strength among the groups. SEM analysis revealed the formation of needle-like apatite crystals from the first day of SBF soaking, and EDS analysis indicated an increase in Ca, P, and Si elements. XRD and FTIR analyses confirmed the presence of apatite. This combination of additives improved the compressive strength and showed the good bioactivity performance of CO3Ap cement, making it a potential biomaterial for bone and dental engineering applications. [ABSTRACT FROM AUTHOR]

Carbonate apatite (CO3Ap) is a major inorganic bone component and an effective bone substitute. To clarify the function of CO3Ap, we compared differences among CO3Ap, hydroxyapatite (HAp), and β-tricalcium phosphate (β-TCP) by focusing on mesenchymal stem cells (MSCs) that have a role in wound healing. For in vivo experiments, maxillary molars were removed and the bone substitute was inserted. MSC accumulation around extraction sockets was significantly promoted in CO3Ap and β-TCP groups. For in vitro experiments, MSCs were cultured with bone substitutes. The differentiation potential and amount of calcium deposition were significantly lower in CO3Ap and HAp groups than in the β-TCP group. Increases in insulin-like growth factor-I and vascular endothelial growth factor were found only in the CO3Ap group. CO3Ap-filled extraction sockets accumulated MSCs, and MSCs cultured in the presence of CO3Ap produced large amounts of growth factors. These results suggest that CO3Ap promotes healing of tooth extraction sockets. [ABSTRACT FROM AUTHOR]

The composition of carbonate apatite (CO3Ap) 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 CO3Ap with an ANP structure without forming excess pores. This study investigated the efficacy of polyurethane foam as a porogen in providing ANP structure to CO3Ap artificial bone. The polyurethane foam was completely decomposed by sintering and the resulting CO3Ap 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 CO3Ap through the interconnected pores accelerated bone regeneration in the ANP‐structured CO3Ap. Thus, this indicates that using polyurethane foam as a porogen endows the CO3Ap artificial bone with an ANP structure that accelerates bone regeneration. [ABSTRACT FROM AUTHOR]

Carbonated apatite is the inorganic component of natural bone while the carbonate ion in the structure influences biological activities and osteoconductivity. However, thermal stability of carbonate apatite is a major importance since thermal stability of carbonate apatite is a function of carbonate content presented in the structure and heat treatment atmosphere. This research work investigates the effects of different carbonate contents on carbonate substitution, thermal stability, physical and mechanical properties of carbonate apatite synthesized by a precipitation method. The results indicated that the carbonate content influenced the properties of carbonated apatite powders. High carbonate substitution (10-11 wt.%) promoted the decomposition of carbonated apatite after heat treatment at 900 °C while a low amount of carbonate substitution (approx. 2 wt.%) resulted in the relocation of carbonate group from phosphate site to hydroxyl site without decomposition. It also demonstrated that a high carbonate amount resulted in a superior mechanical performance. Dense carbonated apatite with high carbonate content has achieved a relative density of 97% and a maximum fracture toughness of 1.4 MPa•m1/2. In the contrary, low carbonate content resulted in a compact with high porosity of about 40% and a low toughness value of 0.35 MPa·m1/2 when treatment at 900 °C. [ABSTRACT FROM AUTHOR]

Abstract Background Low bone quantity and quality are serious problems that affect the prognosis of implants in the cosmetic field. Therefore, artificial bone substitutes are frequently used. However, whether there is a difference in the effect of either bone substitute on soft tissue healing is unclear given their greatly different absorbability. In this study, we used hydroxyapatite (HAp) and carbonate apatite (CO3Ap) as bone substitutes to analyze the epithelial and connective tissue healing after tooth extraction. Methods In vitro, oral mucosa-derived epithelial cells (OECs) collected from 4-day-old Wistar rats were seeded on HAp or CO3Ap and evaluated for adhesion, proliferation, migration, apoptosis, and morphology. Fibroblasts (FBs) were also analyzed for their ability to express collagen. In vivo, the extraction of maxillary right first (M1) and second molars (M2) of 6-week-old male Wistar rats was performed, followed by insertion of HAp or CO3Ap granules into the M1 and M2 sites. The oral mucosal healing process was then evaluated histochemically after 7 and 14 days. Results In vitro, high collagen expression by FBs in the CO3Ap group was observed and the surface analysis showed spreading of the FBs on the CO3Ap surface. However, the activity of OECs was suppressed on CO3Ap. Two weeks after CO3Ap implantation, soft tissue healing was observed, and recovery of the connective tissue was observed on the remaining CO3Ap. Conclusions Our results suggest that the formation of soft tissues, including connective tissue, was promoted by CO3Ap in the extraction socket within a short period.

We have developed an autologous transplantation method using adipose tissue-derived multi-lineage progenitor cells (ADMPCs) as a method of periodontal tissue regeneration that can be adapted to severe periodontal disease. Our previous clinical study confirmed the safety of autologous transplantation of ADMPCs and demonstrated its usefulness in the treatment of severe periodontal disease. However, in the same clinical study, we found that the fibrin gel used as the scaffold material might have caused gingival recession and impaired tissue regeneration in some patients. Carbonate apatite has a high spacemaking capacity and has been approved in Japan for periodontal tissue regeneration. In this study, we selected carbonate apatite as a candidate scaffold material for ADMPCs and conducted an in vitro examination of its effect on the cellular function of ADMPCs. We further performed autologous ADMPC transplantation with carbonate apatite as the scaffold material in a model of one-wall bone defects in beagles and then analyzed the effect on periodontal tissue regeneration. The findings showed that carbonate apatite did not affect the cell morphology of ADMPCs and that it promoted proliferation. Moreover, no effect on secretor factor transcription was found. The results of the in vivo analysis confirmed the space-making capacity of carbonate apatite, and the acquisition of significant new attachment was observed in the group involving ADMPC transplantation with carbonate apatite compared with the group involving carbonate apatite application alone. Our results demonstrate the usefulness of carbonate apatite as a scaffold material for ADMPC transplantation. [ABSTRACT FROM AUTHOR]

Carbonate apatite (CO3Ap) granules are useful as a bone substitute because they can be remodeled to new natural bone in a manner that conforms to the bone remodeling process. However, reconstructing large bone defects using CO3Ap granules is difficult because of their granular shape. Therefore, we fabricated CO3Ap honeycomb blocks (HCBs) with continuous unidirectional pores. We aimed to elucidate the tissue response and availability of CO3Ap HCBs in the reconstruction of rabbit mandibular bone defects after marginal mandibulectomy. The percentages of the remaining CO3Ap area and calcified bone area (newly formed bone) were estimated from the histological images. CO3Ap area was 49.1 ± 4.9%, 30.3 ± 3.5%, and 25.5 ± 8.8%, whereas newly formed bone area was 3.0 ± 0.6%, 24.3 ± 3.3%, and 34.7 ± 4.8% at 4, 8, and 12 weeks, respectively, after implantation. Thus, CO3Ap HCBs were gradually resorbed and replaced by new bone. The newly formed bone penetrated most of the pores in the CO3Ap HCBs at 12 weeks after implantation. By contrast, the granulation tissue scarcely invaded the CO3Ap HCBs. Some osteoclasts invaded the wall of CO3Ap HCBs, making resorption pits. Furthermore, many osteoblasts were found on the newly formed bone, indicating ongoing bone remodeling. Blood vessels were also formed inside most of the pores in the CO3Ap HCBs. These findings suggest that CO3Ap HCBs have good osteoconductivity and can be used for the reconstruction of large mandibular bone defects. [ABSTRACT FROM AUTHOR]

Bone augmentation using artificial bone is an important option in dental defect prostheses. A bone substitute using carbonate apatite (CO3Ap), an inorganic component of bone, was reported to have promising bone formation and bone replacement ability. However, the osteoinductivity of artificial bone is less than autogenous bone (AB). In this study, CO3Ap with AB is demonstrated as a clinically effective bone substitute. For in vitro experiments, an osteoclast-like cell (RAW-D) was cultured in the presence of AB, CO3Ap, or both (Mix), and the number of osteoclasts was evaluated. Osteoblasts were also cultured under the same conditions, and the number of adherent cells was evaluated. For in vivo experiments, a few holes were created in the rat tibia and AB, CO3Ap, or Mix were added. At 0, 14, and 21 days, the tissue morphology of the wound area was observed, and the thickness of the cortical bone was measured. In vitro, Mix did not increase the number of osteoclasts or osteoblasts. However, in vivo, the rate of bone replacement remarkably increased with Mix on dome-shape. A bone-grafting material combining osteoinductive AB with abundant artificial bone is expected to be clinically easy to use and able to form bone. [ABSTRACT FROM AUTHOR]