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β-Tricalcium Phosphate (β-TCP), one of the most used bone graft substitutes, may contain up to 5 wt% foreign phase according to standards. Typical foreign phases include β-calcium pyrophosphate (β-CPP) and hydroxyapatite (HA). Currently, the effect of small amounts of impurities on β-TCP resorption is unknown. This is surprising since pyrophosphate is a very potent osteoclast inhibitor. The main aim of this study was to assess the effect of small β-CPP fractions (, Graphical abstract Image 1, Highlights • Purest β-TCP cylinders ever reported in the literature. • Bulk Ca/P molar ratio influences the physico-chemical properties of β-TCP cylinders. • White light interferometry is a potent method to quantify osteoclastic resorption. • The presence of 1% of β-CPP reduces the in vitro β-TCP resorption rate by 40%.

Актуальность. В структуре всех переломов скелета человека переломы пяточной кости составляют от 2,0 до 5,7 %, в структуре переломов костей стопы — до 40–60 %, они преобладают среди физически активных лиц трудоспособного возраста. Интраартикулярными переломы пяточной кости являются в 75–92 % случаев, носят импрессионный характер и могут быть предпосылкой развития посттравматического деформирующего остеоартроза суставов заднего отдела стопы. Сохраняется высокий процент неудовлетворительных результатов лечения — 13,0–27,3 %. Цель: исследовать и проанализировать результаты хирургического лечения внутрисуставных импрессионных переломов пяточной кости с применением аутокости и биокомпозита керамического материала игольчатой структуры на основе β-трикальцийфосфата в составе гранул биомин ГТ mix. Материалы и методы. В исследовании приняли участие 47 больных с внутрисуставными импрессионными переломами 50 пяточных костей, лечившихся оперативным путем на клинических базах кафедры общей хирургии и травматологии-ортопедии Ужгородского национального университета в период 2014–2018 гг. 10 пациентам проводили открытую репозицию в сочетании с опорной остеопластикой аутотрансплантатом с гребня крыла подвздошной кости, 37 больным — с остеопластикой биомином ГТ mix. Результаты. Результаты хирургического лечения были изучены в сроки 3, 6, 12 и 18 месяцев, оценены в соответствии со шкалой American Orthopedic Foot and Ankle Society Ankle Hindfoot Score. В 18 месяцев отличные результаты достигнуты у 11 пациентов, хорошие — у 18, удовлетворительные — у 10, неудовлетворительные — у 4 человек. Выводы. Опорная остеопластика биомином ГТ mix наравне с применением аутокости является эффективным способом костной пластики при хирургическом лечении внутрисуставных импрессионных переломов пяточной кости.

Objectives: An in-vitro study was designed to investigate the antimicrobial activity of β-tricalcium phosphate/calcium sulfate in comparison to Xenograft, blended with either gentamicin or saline. Methods and materials: Employing Kerby-Bauer disk diffusion test,twelve Petri dishes (90 mm) with two models of culture mediums were used to cultivate three bacterial strains: Muller-Hinton Agar (for P. Aeruginosa/S. Aureus)andSheep Blood Agar (for Enterococcus faecalis).Then, studied materials were divided into four groups (Bovine, Bovine with gentamicin, EthOss and EthOss with gentamicin), mixed-upand transmittedinto their holes in each dish. After 24h of incubation, inhibition zones were noted and measured bya digital caliper.In the end statistical analysis were completed with One Way ANOVA followed by Tuckey HSD test on SPSS17. Results: One Way ANOVA and Tuckey HSD remarked astatically significant difference between all pairs for Enterococcus faecalis (p

Beta-tricalcium phosphate ( β-TCP) refers to one ideal bone repair substance with good biocompatibility and osteogenicity. A digital light processing (DLP)-system used in this study creates bioceramic green part by stacking up layers of photocurable tricalcium phosphate-filled slurry with various β-TCP weight fractions. Results show that the sintering shrinkage is anisotropic and the shrinkage vertically reaches over that horizontally. The obtained porous β-TCP parts have both macroporous outer structure and microporous inner structure, the macropore size is 400–600 μm and the micropore size is 500–1500 nm. The mechanical tests show that the porous β-TCP bioceramic’s compressive strength reaches 16.53 MPa. The cell culture confirmed that the porous β-TCP bioceramic is capable of achieving the effective attaching, growing, and proliferating pertained to mouse osteoblast cells. This study identified considerable blood vessels and significant ectopic bone forming obviously based on the histologically-related assessment when implanting to rabbit femoral condyle deficiency for 3 months. Thus, under high bioactive property and osteoinductivity, and large precision and mechanical strength that can be adjusted, the DLP printed porous β-TCP ceramics is capable of being promising for special uses of bones repairing.

β-tricalcium phosphate bioceramics suffer from a drawback of poor mechanical strength and a scarcity of capacity to regulate biological performances. In the current study, the overall performances of β-tricalcium phosphate (TCP) bioceramics were improved by incorporating calcium silicate (CS) and magnesium-strontium phosphate (MSP). During the sintering process, the MSP stabilized the β phase of TCP, and the formation of MSP melt ensured effective liquid-sintering of TCP, thus conducing to lower porosity of TCP/MSP and TCP/CS/MSP bioceramics. In comparison with the TCP bioceramics, the TCP/CS and TCP/MSP bioceramics showed lower compressive strength, while the TCP/CS/MSP bioceramics attained noticeably higher compressive strength. Due to the sustained release of therapeutical ions, the TCP/CS bioceramics enhanced in vitro early-stage osteoblastic differentiation, but compromised cell proliferation; both the TCP/MSP and TCP/CS/MSP bioceramics enhanced cell proliferation and osteoblastic differentiation, and restrained osteoclastic activities. Collectively, the TCP/CS/MSP bioceramics with optimal overall performances are promising for efficaciously treating the defects of osteoporotic bone.

Advanced fabrication methods for bone grafts designed to match defect sites that combine biodegradable, osteoconductive materials with potent, osteoinductive biologics would significantly impact the clinical treatment of large bone defects. In this study, we engineered synthetic bone grafts using a hybrid approach that combined three-dimensional (3D-)printed biodegradable, osteoconductive β-tricalcium phosphate (β-TCP) with osteoinductive microRNA(miR)-200c. 3D-printed β-TCP scaffolds were fabricated utilizing a suspension-enclosing projection-stereolithography (SEPS) process to produce constructs with reproducible microarchitectures that enhanced the osteoconductive properties of β-TCP. Collagen coating on 3D-printed β-TCP scaffolds slowed the release of plasmid DNA encoding miR-200c compared to noncoated constructs. 3D-printed β-TCP scaffolds coated with miR-200c-incorporated collagen increased the transfection efficiency of miR-200c of both rat and human BMSCs and additionally increased osteogenic differentiation of hBMSCs in vitro. Furthermore, miR-200c-incorporated scaffolds significantly enhanced bone regeneration in critical-sized rat calvarial defects. These results strongly indicate that bone grafts combining SEPS 3D-printed osteoconductive biomaterial-based scaffolds with osteoinductive miR-200c can be used as superior bone substitutes for the clinical treatment of large bone defects.

Objective: Osteochondral defect presents a big challenge for clinical treatment. This study aimed at constructing a bi-layered composite chitosan/chitosan-β-tricalcium phosphate (CS/CS-β-TCP) scaffold and at repairing the rat osteochondral defect. Approach: The bi-layered CS/CS-β-TCP scaffold was fabricated by lyophilization, and its microstructure was observed by a scanning electron microscope. Chondrocytes and bone marrow stem cells (BMSCs) were seeded into the CS layer and the CS-β-TCP layer, respectively. Viability and proliferation ability of the cells were observed under a confocal microscope. After subcutaneous implantation, the chondrogenic ability of the CS layer and osteogenic ability of the CS-β-TCP layer were evaluated by immunofluorescence. Then, the bi-layered scaffolds were implanted into the rat osteochondral defects and the harvested samples were macroscopically and histologically evaluated. Results: The bi-layered CS/CS-β-TCP scaffold exhibited the distinctive microstructures for each layer. The seeded chondrocytes in the CS layer could maintain the chondrogenic lineage, whereas BMSCs in the CS-β-TCP layer could continually differentiate into the osteogenic lineage. Moreover, cells in both layers could maintain well viability and excellent proliferation ability. For the in vivo study, the newly formed tissues in the bi-layered scaffolds group were similar with the native osteochondral tissues, which comprised hyaline-like cartilage and subchondral bone, with better repair effects compared with those of the pure CS group and the blank control group. Innovation: This is the first time that the bi-layered composite CS/CS-β-TCP scaffold has been fabricated and evaluated with respect to osteochondral defect repair. Conclusion: The bi-layered CS/CS-β-TCP scaffolds could facilitate osteochondral defect repair and might be the promising candidates for osteochondral tissue engineering.

This study aims to compare the effect of fTCP-contained toothpaste in combination with 950 ppm fluoride on primary dentin caries surface to ordinary 1100 ppm fluoride toothpaste by using estimation statistics. Dental caries with deep lesion and dentin exposure from nine primary teeth were cut into two equal parts and randomly divided into two groups in a before-after study. Each group was brushed with one type of toothpaste two times per day for 28 days and rested in artificial saliva. SEM images of cavity bottom surfaces and energy-dispersive X-ray spectrometry (EDX) were used to determine the percentage of calcium (Ca), phosphorus (P), fluoride (F) and oxygen (O) at six continuous measured areas from the surface of the cavity bottom into 45 µm depth before and after brushing. About 95% confidence interval of the mean difference was calculated by performing bootstrap resampling with 5000 resamples followed by comparison analysis. The percentage of Ca, P, F, O was shifted after treatment. There was no difference between the two groups. The SEM images reflected a similar illustration of EDX data. The combination of fTCP and 950 ppm fluoride in toothpaste showed equivalent effectiveness to the 1100 ppm fluoride toothpaste in primary dentin caries.

Calcium-phosphate cements (CPCs) have been used as bone filling materials in orthopaedic surgery. However, CPCs are set using an acid-base reaction, and then change into stable hydroxyapatite (HAp) in a living body. Therefore, we developed bioresorbable chelate-setting β-tricalcium phosphate (β-TCP) cements based on surface modifications of inositol phosphate (IP6). In order to improve the bioresorbability, we fabricated IP6/β-TCP cements hybridized with poly(lactic-co-glycolic acid) (PLGA) particles as a pore-forming agent. The compressive strengths of the cements with the amounts of 5 and 10 mass% PLGA particles were 23.2 and 22.8 MPa, respectively. There was no significant difference from cements without PLGA (23.4 MPa). The setting times of the cement specimens with PLGA particles (30 min) were a little longer than those without PLGA particles (26.3 min). The lack of cytotoxicity of the cement specimens was confirmed using osteoblast-like cells (MC3T3-E1). Cylindrical defects were made by drilling into the tibia of mini-pigs and injecting the prepared cement pastes into the defects. Twelve weeks after implantation the specimens were stained with toluidine blue and histologically evaluated. Histological evaluation of cement specimens with PLGA particles showed enhanced bioresorbability. Newly-formed bone was also observed inside cement specimens with PLGA particles. The IP6/β-TCP cement specimens with PLGA particles had excellent material properties, such as injectability, compressive strength, high porosity, no cytotoxicity in vitro, bioresorption and bone formation abilities in vivo. Organic-inorganic hybridized CPCs are expected to be valuable as novel biodegradable paste-like artificial bone fillers., Graphical abstract

The effect of silane A-174 (3-(trimethoxysilyl)propyl methacrylate (methacryloxypropyl trimethoxysilane)) modifications of the ceramic surface on the structural characteristics and mechanical perfo...

Reconstruction of bone defect due to a disease or a trauma can use autograft, allograft, xenograft or synthetic bonegraft as the bone substitute material. However, in particular cases, it is required a material that has a specific resorption characteristic, beside owning excellent bioactive properties, such as β-tricalcium phosphate (β-TCP). In this study, we report the synthesis of β-TCP particles with mesopores structure by using chitosan and aloe vera as templates. A solution of (NH4)2HPO4 was added dropwise into solution of Ca(NO3)2·4H2O and the template at 85°C for 2 hours, and subsequently aged for 3 hours. Then, the formed precipitate was washed and centrifuged repeatedly prior to drying at 80°C for 24 hours. Finally, the dried precipitate was calcined at 900°C for 1 hour to obtain β-TCP powder. Phase identification and mesopores structure were analyzed using X-ray diffraction (XRD), while the existence of functional groups was identified by Fourier-transform infrared (FTIR) spectroscopy. Microstructure and particle size distribution were characterized by scanning electron microscopy (SEM) and particle size analyzer (PSA), respectively. XRD analysis shows that β-TCP is dominant with the presence of small amount of impurities. Furthermore, low angle peak in XRD analysis indicates the formation of mesopores structure. From the SEM and PSA analysis, the morphology of both TCP-K and TCP-KA particles showed more large agglomerates and more heterogeneous particle size distribution due to the addition of the biopolymers in the synthesis of β-TCP.

The question whether β‐tricalcium phosphate (β‐TCP) can form a solid solution with β-calcium pyrophosphate (β-CPP) and/or hydroxyapatite (HA) has still not been solved. For this reason, wet-chemically synthesized β-TCP powders with only 20 ppm Sr (among 43 tested elements) and with different HA and β-CPP contents, or in other words Ca/P molar ratios, were used. The graphical relationship between these various Ca/P molar ratios determined by X-ray diffraction and by inductively-coupled plasma mass spectrometry showed no discontinuity, indicating the absence of a solid solution between β‐TCP and β-CPP or HA. Analysis of the β‐TCP lattice parameters as a function of the Ca/P molar ratio revealed a discontinuity at a Ca/P molar ratio of 1.500 and a maximum microstrain. These results indicated that at least two β‐TCP structures co-existed, with variable mixing ratios depending on the Ca/P molar ratio, and with a distinct jump at a Ca/P molar ratio of 1.500.

Background: Platelet-rich fibrin (PRF) is the second-generation platelet concentrate first described by Choukron et al. It incorporates leukocytes, platelets, and growth factors within dense fibrin matrix, can be used in periodontal regeneration alone or in combination with bone grafts. Aim: This study assesses bone fill in intrabony defects, following the use of β tricalcium phosphate (TCP) bone graft with and without PRF. Materials and Methods: Thirty sites with intrabony defects in periodontitis patients were selected, randomly allotted into three groups: Group A open flap debridement (OFD), Group B OFD with β TCP with PRF, and Group C β TCP. Clinical parameters such as plaque index, gingival index, sulcus bleeding index, and PPD recorded at baseline and 6 months. Radiographic parameters include cementoenamel junction (CEJ) to base of defect, CEJ to alveolar crest, depth of defect, and bone fill assessed using the cone-beam computed tomography (CBCT). The comparison between the test group and control group in terms of clinical and radiographical parameters was assessed using the independent sample t-test. Results: Significant reduction in probing depth measurements, defect fill observed in both β TCP with PRF and β TCP alone groups compared to OFD. However, intergroup comparison assessed using the independent sample t-test found to be statistically nonsignificant (P < 0.05 is considered significant). Conclusion: All three treatment strategies resulted in significant reduction in probing depth and bone fill at 6 months. Bone fill achieved in β TCP with PRF was more compared to β TCP alone and OFD at 6 months follow-up. CBCT can be accurately used to assess the morphology of intrabony defect and also in evaluating bone fill.

Introduction: Unidirectional porous β-tricalcium phosphate (UDPTCP) consists of a novel porous artificial bone that is structurally different from conventional artificial bone comprised of spherical porous β-tricalcium phosphate (SPTCP). Case presentation: We present our first four clinical cases of opening-wedge high tibial osteotomy (OWHTO) using UDPTCP and SPTCP together. The patients’ mean age was 54.5 ± 5.9 years, and the mean observation period was 20.8 ± 2.8 months. In OWHTO, two wedge shaped pieces of UDPTCP and SPTCP were cut to fit the gap and implanted parallel to each other in the anterior and posterior parts, respectively. We evaluated the correction loss and bone remodeling for UDPTCP and SPTCP over time using radiography and computed tomography, and evaluated the clinical outcomes. Conclusion: There was no correction loss reported in any case, and early bone remodeling was observed with UDPTCP. All patients achieved satisfactory clinical results with no adverse events.

In this study we compared the bone remodeling of unidirectional (UDPTCP) and spherical porous β-tricalcium phosphate (SPTCP) radiologically in humans. We performed a retrospective analysis of the data of 14 patients (sex, nine men and five women; age, 37–70 years) who underwent medial opening-wedge high tibial osteotomy (MOWHTO) and were followed up for 12 months after surgery. Two wedge-shaped β-TCPs (one UDPTCP and one SPTCP) were cut and placed parallel to each other in the gap. In Group A (eight knees), UDPTCP was implanted anteriorly and SPTCP posteriorly, while in Group B (six knees), SPTCP was implanted anteriorly and UDPTCP posteriorly. Computed tomography (CT) was performed at 1 week, 6 months, and 12 months after surgery, with the CT attenuation values calculated for UDPTCP and SPTCP. In Groups A and B, the CT attenuation values for UDPTCP were significantly lower at 6 and 12 months after surgery compared to those at 1 week (P

The aim of this study is to investigate the behavior of osteoclast cells response on dicalcium phosphate dihydrate (DCPD) layer-coated β-TCP granules. β-TCP granules with 300-600 μm were exposed to acidic calcium phosphate solution for 30 mins in order to get 10 mol% DCPD layer-coated β-TCP granular. DCPD free-coated β-TCP granular had used as control specimen. Both specimens were implant in 9 mm of rat calvarial bone defect for 4 weeks. After 4 weeks, the block section of rat calvarial containing specimen were removed for Tatrate-Resistance Acid Phosphatase (TRAP) analysis. Results of TRAP staining reveal that the number of osteoclast cells attached on 10 mol% layer-coated β-TCP granular is higher than DCPD free-coated β-TCP granular. Since remodeling of new bone formation involved simultaneous osteoclast and osteoblast cells response, therefore, the results obtained in this study indicated that the presence of DCPD layer-coated on β-TCP granular helps to improve osteoclast cells response that contribute in stimulating new bone formation.

Reducing the viscosity of high solid-loading ceramic suspensions and controlling the resolution of ceramic green parts produced by digital light processing (DLP) 3D printing are two important concerns in the ceramic additive manufacturing industry. The presence of ceramic particles within a photopolymerizable system leads to light scattering that reduces the resolution of the ceramic green scaffolds. This study introduced a graphite additive to solve these problems and focused on the effects of graphite concentration on the viscosity, curing behaviour and scaffold fabrication of β-TCP ceramic suspensions. As a result, it was found that an appropriate addition of graphite reduced the viscosity of the ceramic suspensions, and the light scattering decreased with the increase of graphite concentration. Both the cure depth (Cd) and excess width (Cex) also decreased with the increase of graphite concentration. But, graphite has a larger effect on the width curing than depth curing.

Gokcekaya O., Ueda K., Narushima T., et al. Using HAADF-STEM for atomic-scale evaluation of incorporation of antibacterial Ag atoms in a ß-tricalcium phosphate structure. Nanoscale, 12, 31, 16596. https://doi.org/10.1039/d0nr04208k., Structural evaluation of ionic additions in calcium phosphates that enhance their performance is a long-lasting area of research in the field of biomedical materials. Ionic incorporation in ß-tricalcium phosphate (ß-TCP) structures is indispensable for obtaining desirable properties for specific functions and applications. Owing to its complex structure and beam-sensitive nature, determining the extent of ion incorporation and its corresponding location in the ß-TCP structure is challenging. Further, very few experimental studies have been able to estimate the location of Ag atoms incorporated in a ß-TCP structure while considering the associated changes in lattice parameters. Although the incorporation alters the lattice parameters, the alteration is not significant enough for estimating the location of the incorporated Ag atoms. Here, Ag incorporation in a ß-TCP structure was evaluated on atomic scale using scanning transmission electron microscopy (STEM). To the best of our knowledge, this is the first report to unambiguously determine the location of the incorporated Ag atoms in the ß-TCP structure by comparing z-contrast profiles of the Ag and Ca atoms by combining the state-of-art STEM observations and STEM image simulations. The Ag incorporation in the Ca(4) sites of ß-TCP, as estimated by the Rietveld refinement, was in good agreement with the high-angle annular dark-field STEM observations and the simulations of the location of Ag atoms for [001] and [010] zone axes.

Background: To assess the clinical and histomorphometric data of the new bone tissue from a mixture of autologous bone and β-tricalcium phosphate. Materials and methods: A total of 72 two-stage sinus lift were performed in 54 patients during 2007 to 2010. The autologous bone was harvested from the mandibular ramus and mixed with the β-tricalcium phosphate Poresorb® TCP sized 1-2 mm. The materials were used in a proportion ranged between 1:1 and 1:3. After the healing period a total of 119 implants were placed and 10 samples of the regenerated bone were collected for the histomorphometric analysis. CBCT or panoramic X-rays were performed presurgically, before the implant placement, six months after implant placement and then yearly to evaluate the bone formation and marginal bone loss. The implant success rate was determined using the Albrektsson et al. Criteria. Results: The mean of the residual bone was 4.07 mm ± 1.87 mm. The bone gain in the sinus was 11.91 mm ± 2.80 mm. The implant success rate was 94.95%. The histomorphometric measurements on the biopsies showed a bone area mean of 39.7 ± 9.71%. The residual allograft area was 16.21 ± 8.78%. The connective tissue was 44.16 ± 5.85%. Conclusion: Within the limit of this study, the osteoconductive β-tricalcium phosphate associated with autologous bone is a viable grafting material for sinus lift procedures. The use of composite grafts can help to reduce the morbidity and aggressivity of the bone harvesting. Keywords: Sinus lift; Bone regeneration; Dental implants; β-tricalcium phosphate; Bone graft; Bone atrophy

Calcium phosphate is widely used as an implant material in the biomedical field, mainly because they are chemically similar to the inorganic components of bones. In many applications, dimensional a...

We succeeded in the electrical polarization of β-tricalcium phosphate (β-TCP) granules and performed an unprecedented attempt to implant them into maxillary bone defects in canines to confirm their ability to facilitate new bone formation. Two holes were drilled into each maxilla half of a canine and filled with electrically polarized and nonpolarized β-TCP granules (grouping assignment was decided randomly). The implanted specimens were dissected en bloc and used for microcomputed tomography (μCT) observations and histological analyses 4 and 8 weeks after the operation. New bone ingrowth in the bone hole progressed over time from the superficial layer of the cortex toward the inner cancellous bone. The percentage area of new bone in the bone hole, as measured by μCT in the sagittal plane, was significantly larger after 4 and 8 weeks, and that measured by H&E-stained specimens in the transverse plane after 4 weeks was significantly larger in the polarized group than in the nonpolarized group. In addition to the structural stability and chemical characteristics of the β-TCP granules, electrical stimulation bears influence not indirectly but directly on osteogenic and vessel cells, which might work cooperatively for the early initiation of the bone formation process.

Polymeric/ceramic composite scaffolds that are biocompatible and biodegradable are widely used for tissue engineering applications. In this work a series of poly(L-lactide-co-glycolide-co-e-caprola...

Material composition and porous structure are important factors in the formation and maturation of newly formed bone and replacement of materials by new bone. Conventional bone graft materials often lack suitability for bone generation because of the complexity of their macroporous structures, which can interfere with the penetration of cells related to bone remodeling and angiogenesis in the materials. In the present study, carbonate apatite (CO

The aim of this study is to investigate the efficacy and the effect of the dosage of the slow-released Escherichia coli-derived recombinant human bone morphogenetic protein 2 (ErhBMP-2) functionalized β-tricalcium phosphate (β-TCP) in repairing critical-sized bone defects. The functionalization was implemented by modifying the surface of β-TCP with biomimetic calcium phosphate coating with or without ErhBMP-2. Critical-sized calvarial defects were created in rats and filled with ErhBMP-2 functionalized β-TCP loaded with gradient doses of ErhBMP-2 (0, 50, 100, 150, 200, and 300 μg/g). The blank control group and the autologous bone group were also included. The systemic toxicity was evaluated using routine blood and histopathological examination. The efficiency in bone healing was evaluated using microcomputed tomography, histology, and histometric analyses. Neither local nor systemic adverse effects were found following the implantation of the ErhBMP-2 functionalized β-TCP. The new bone formation was significantly increased in the ErhBMP-2 functionalized β-TCP groups compared with the blank group and the β-TCP with coating only group. The efficacy of the ErhBMP-2 functionalized β-TCP in bone healing was comparable to that of the autologous bone. There was no significant difference in bone formation among all concentrations of ErhBMP-2 (0-300 μg/g). Increased bone maturation was found in the higher concentration groups (150, 200, and 300 μg/g) when compared with the lower concentration groups (50, and 100 μg/g). Our results demonstrated that the ErhBMP-2 functionalized β-TCP could significantly promote bone repairing in critical-sized defects, and it could clinically be a promising substitute for autologous bone. Besides, our results demonstrated that there was a dosage-dependent effect of ErhBMP-2 functionalized β-TCP on bone maturation rather than bone formation. The optimized concentrations of ErhBMP-2 recommended for this kind of model should be in the range of 150-300 μg/g. Bone substitutes functionalized by mammalian-derived recombinant human bone morphogenetic protein 2 (rhBMP-2) have demonstrated to be comparable to the autologous bone in repairing the critical-sized bone defects. To develop a commercial product with more effective cost, Escherichia coli-derived rhBMP-2 (ErhBMP-2) has been produced and evaluated as an alternative to the mammalian-derived rhBMP-2. In this study, we prepared gradient ErhBMP-2 functionalized β-tricalcium phosphate (β-TCP) with biomimetic calcium phosphate coating and investigate their efficacy and dose effects. We revealed the dose effects of the slow-released ErhBMP-2 and demonstrated that ErhBMP-2 functionalized β-TCP could be a promising bone substitute for bone regeneration in clinical settings.

Hip replacement is one of the most effective surgical procedures in medicine. Despite the fact that the clinical results of arthroplasty are usually excellent, some implants loosen with time and require revision. To help resolve this problem, research has focused on providing conditions that have a positive biological effect on bone building elements, resulting in a fast, seamless proliferation and differentiation of mesenchymal stem cells (MSC) into osteoblasts. That is why developing an in vitro model for studying MSC functions at the implant–tissue contact zone is essential. The aim of this study was to investigate the proliferation and differentiation capacity of human bone-marrow derived MSC in contact with medical implant-grade Ti-6Al-4V alloy and β-tricalcium phosphate (β-TCP). Human MSC were isolated from bone marrow aspirates obtained from the femoral canal during hip replacement surgeries and seeded on Ti-6Al-4V alloy squared specimens and β-TCP granules. The results indicate that MSC were able to effectively adhere to both biomaterial surfaces and, at the same time, retain their proliferative and osteogenic/adipogenic differentiation potential. We suggest that both Ti-6Al-4V alloy and β-TCP surfaces provide suitable conditions for the proliferation and differentiation of bone marrow MSC and can be used as in vitro models to explore MSC functions at the bone–implant interface.

Pore structure plays an important role in the in vivo osteogenesis for bone repair materials. In this study, honeycomb β-tricalcium phosphate (β-TCP) scaffolds were prepared by extrusion method, and gelatin microspheres were used as porogens to modify the pore structure of the scaffolds. The honeycomb β-TCP scaffolds were characterized by channel-like square macropores and unidirectional interconnection. To improve the pore interconnectivity of the scaffold, the spherical pores were formed in the channel walls by burning off the gelatin microspheres. Compared with unidirectional honeycomb β-TCP scaffold, the honeycomb β-TCP scaffold with interconnected pore structure had significantly higher porosity and faster degradation rate, at the expense of the mechanical strength. The in vivo assessment results demonstrated excellent osteogenesis of the honeycomb scaffolds. Moreover, the honeycomb β-TCP scaffold with interconnected pore structure markedly promoted new bone formation in comparison with the unidirectional honeycomb β-TCP scaffold. This work provides a new approach to prepare scaffolds with interconnected pore structure, and the honeycomb β-TCP scaffold with interconnected pore structure is expected to serve as an efficient bone repair material.

Introducction This research aimed to investigate the effect of antibacterial suspension containing TCP-β and nanosilver on these pathogens. Material and methods : Suspension containing concentrations of 4%, 2%, 1% and 0.1% was prepared with tricalcium phosphate and nanosilver. Two control suspensions for pure nanosilver and pure β-TCP were also prepared. The antibacterial activity of this suspension was investigated on two groups of bacteria, namely, P. intermedia and Aa in thioglycolate broth environment. Subsequently, the MIC was measured for each bacterium. Results The suspension containing β-TCP and nanosilver produced an antibacterial effect on P. intermedia and Aa. The effect of this solution on P. intermedia was greater than that on A. actinomycetemcomitans. Moreover, the MICs (mg/mL) for P. intermedia and A. actinomycetemcomitans were 1% and 0.1%, respectively. Conclusion Based on the results of this study adding nanosilver particles to β-TCP resulted in the antibacterial property of this substance. Specifically, reduced the growth rate of Aa and P. intermedia. Nanosilver can be used to reduce the risk of infection during or after regenerative surgery.

Porous β-tricalcium phosphate (β-TCP) foam granular cements was obtained by exposing different range size of β-TCP foam granular (300-600 μm and 600-1000 μm) with 1.4 mol/L of saturated acidic calcium phosphate solution at various setting reaction times. It was found that large amount of dicalcium phosphate dihydrate (DCPD) was formed in the set specimens after exposing small size of β-TCP foam granular with saturated acidic calcium phosphate solution. Morphological observation shows that the bridging of DCPD platelet-like crystals between β-TCP foam granular surfaces were detected as early as 10 mins after exposing 300-600 μm of β-TCP foam granules with saturated acidic calcium phosphate solution. In fact, the amount of DCPD formed in the specimens obtained from small size of β-TCP foam granules is higher than large sized foam granules. These results demonstrated that small size of β-TCP foam granules induced fast setting reaction of β-TCP foam granules to produce porous β-TCP foam granular cements.

BACKGROUND β-Tricalcium phosphate (β-TCP) is one of the most common synthetic bone grafting materials utilized in craniofacial reconstruction; however, it is limited by a slow degradation rate. The aim of this study was to leverage 3-dimensional (3D) printing in an effort to accelerate the degradation kinetics of β-TCP. METHODS Twenty-two 1-month-old New Zealand white rabbits underwent creation of calvarial and alveolar defects, repaired with 3D-printed β-TCP scaffolds coated with 1000 μM of osteogenic agent dipyridamole. Rabbits were euthanized after 2, 6, and 18 months after surgical intervention. Bone regeneration, scaffold degradation, and bone mechanical properties were quantified. RESULTS Histological analysis confirmed the generation of vascularized and organized bone. Microcomputed tomography analysis from 2 to 18 months demonstrated decreased scaffold volume within calvarial (23.6% ± 2.5%, 5.1% ± 2.2%; P < 0.001) and alveolar (21.5% ± 2.2%, 0.2% ± 1.9%; P < 0.001) defects, with degradation rates of 54.6%/year and 90.5%/year, respectively. Scaffold-inducted bone generation within the defect was volumetrically similar to native bone in the calvarium (55.7% ± 6.9% vs 46.7% ± 6.8%; P = 0.064) and alveolus (31.4% ± 7.1% vs 33.8% ± 3.7%; P = 0.337). Mechanical properties between regenerated and native bone were similar. CONCLUSIONS Our study demonstrates an improved degradation profile and replacement of absorbed β-TCP with vascularized, organized bone through 3D printing and addition of an osteogenic agent. This novel additive manufacturing and tissue engineering protocol has implications to the future of craniofacial skeletal reconstruction as a safe and efficacious bone tissue engineering method.

This research presents the effect of heat treatment temperature on the forming ability of β-tricalcium phosphate (β-TCP) bioceramic materials toward the bone tissue regeneration application. Ca(OH)2 and H3PO4 were mixed with a Ca/P molar ratio of 1.5, followed by hydrothermal treatment at 180oC for 24 hours to obtain the calcium phosphate hydrate (CPH) with phase composition similar to hydroxyapatite (HA). The CPH mineral was heat-treated at 700 and 1000oC for 3 hours to evaluate the ability to obtain β-TCP. The result showed that β-TCP can be obtained by the CPH calcined at 1000oC for 3 hours, with the particle size of 1~2 μm, suitable for bone tissue regeneration application.

Fibrocartilaginous entheses are structurally complex tissues that translate load from elastic ligaments to stiff bone via complex zonal organization with gradients in organization, mineralization, and cell phenotype. Currently, these gradients, necessary for long-term mechanical function, are not recreated in soft tissue-to-bone healing or engineered replacements, leading to high failure rates. Previously, we developed a culture system which guides ligament fibroblasts to develop aligned native-sized collagen fibers using high density collagen gels and mechanical boundary conditions. These constructs hold great promise as ligament replacements, however functional ligament-to-bone attachments, or entheses, are required for long-term function in vivo. The objective of this study was to investigate the effect of compressive mechanical boundary conditions and the addition of beta tricalcium phosphate (βTCP), a known osteoconductive agent, on the development of zonal ligament-to-bone entheses. We found that compressive boundary clamps, that restrict cellular contraction and produce a zonal tensile-compressive environment, guide ligament fibroblasts to produce 3 unique zones of collagen organization, and zonal accumulation of glycosaminoglycans (GAGs), type II and type X collagen by 6 weeks of culture, ultimately resulting in similar organization and composition as immature bovine entheses. Further, βTCP under the clamp enhanced the maturation of these entheses, leading to increased GAG accumulation, sheet-like mineralization, and significantly improved tensile moduli, suggesting the initiation of endochondral ossification. This culture system produced some of the most organized entheses to date, closely mirroring early postnatal enthesis development, and provides an in vitro platform to better understand the cues that drive enthesis maturation in vivo.

Background: Fracture repair is one of most common procedure carried out by veterinary clinicians. Fracture healing most of the time associated with delayed union, non-union and mal-uinon. Therefore, the objective of this study was to evaluate the clinical, haemato-biochemical and radiological outcome in patients after implantation of β-tricalcium phosphate as a bone graft substitute to promote the fracture healing.Methods: Eight clinical cases brought to the clinics with femur fracture were divided into two groups viz. A and B, with four animals in each group. Femur fractures were stabilized with intramedullary pinning and β-TCP biomaterial and intramedullary pinning and β-TCP plus autologous bone marrow aspirate (BMA) composite in group A and B respectively. The efficacy of fixation was studied on the basis of clinical evaluation, haemato-biochemical and radiographical parameters on day 0 and on 7th, 15th, 30th, 45th and 60th post-operative day. Result: Excellent weight bearing was noticed in group B. The overall functional outcome in group B was better in comparison to group A animals. Haematological parameters viz. haemoglobin, packed cell volume, total leukocyte count and differential leukocyte count did not differ significantly within and between the groups. The biochemical parameters viz. serum calcium increased significantly (P less than 0.05) on 7th and 15th post-operative day. A significant reduction in serum alkaline phosphatase level observed on successive post-operative days in both groups. Radiographs of fractures treated in both the groups showed good reduction and fracture fixation, early signs of fracture healing in group B than group A animals. The size of callus formation was more in group A than group B. No any graft related complications observed during the study period. The β-tricalcium phosphate facilitated fracture healing and early ambulation of affected limb.

Purpose Autografts, the gold standard treatment for large bone defects, present complications, especially in conditions with reduced bone-repair capacity, such as osteoporosis. Escherichia coli-derived recombinant human bone morphogenesis protein-2 (ErhBMP-2), was used in this study to improve the osteoinductivity of β-tricalcium phosphate (β-TCP). This study evaluated the bone-repair capacity of ErhBMP-2-loaded β-TCP on osteoporosis rabbit model, relative to the sole use of autograft and β-TCP treatments. Methods The osteoporosis rabbit model was induced through ovariectomy and glucocorticoid dosing; 2-cm segmental ulnar defects were created, which were treated with either autograft, β-TCP alone, or ErhBMP-2-loaded β-TCP or left untreated. The quality of newly formed ulnae was evaluated 8 weeks after ulnar surgery through micro-CT, biomechanical, histological, and histomorphometric assessments. Results The osteoporosis rabbit model was developed and maintained till the end of the study. The maximal load and stiffness in the ErhBMP-2-loaded TCP group were significantly higher than those in the autograft group, whereas the TCP-alone group performed similarly as did the untreated group in the force loading and stiffness tests. According to the micro-CT evaluation, the ErhBMP-2-loaded TCP group had significantly higher bone volume relative to the autograft and TCP-alone groups. Histological assessments revealed better defect bridging and marrow formation in the ErhBMP-2-loaded TCP group relative to the TCP-alone group. Mineral apposition rates were significantly higher in the ErhBMP-2-loaded TCP and autograft groups than in the TCP-alone and untreated groups. Conclusion Relative to autografts, ErhBMP-2-loaded TCP, as an alternative grafting material, provides better or comparable healing on critical-sized long bone defects in the osteoporosis rabbit model., Graphical abstract Unlabelled Image, Highlights • Erh-BMP-2 promoted the bone healing ability of β-TCP in osteoporosis animal model. • New bone generated by Erh-BMP-2-loaded β-TCP was stiffer than that generated by autograft. • ErhBMP-2-loaded TCP potentially being an alternative grafting material relative to autograft.

β-tricalcium phosphate (β-TCP)/ԑ-polycaprolactone (PCL) composite scaffolds with a controllable gradient were developed with a two-step process: fabrication of the β-TCP scaffolds using digital light processing (DLP) 3D printing and then immersion of the β-TCP scaffolds into a PCL melt for different times. The gradient structure was controlled by the immersion time of the β-TCP scaffolds in the molten PCL. The composite scaffolds with a gradient exhibited a substantially higher compressive strength and toughness than the bare β-TCP scaffolds. Moreover, the increase in infiltration time also enhanced the compressive strength and toughness of the composite scaffolds because the infiltration thickness increased with infiltration time. The gradient structure resulted in a gradient degradation and may provide a better response to time-varying mechanical properties than pure β-TCP scaffolds during its absorption process. Therefore, composite scaffolds with a gradient are promising candidates for load-bearing bones or large segmental bone repair.