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ABSTRACT: Objectives: The purpose of this work was to optimise printable polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP) biomaterials with high percentages of β-TCP endowed with balanced mechanical characteristics to resemble human cancellous bone, presumably improving osteogenesis. Methods: PCL/β-TCP scaffolds were obtained from customised filaments for fused deposition modelling (FDM) 3D printing with increasing amounts of β-TCP. Samples mechanical features, surface topography and wettability were evaluated as well as cytocompatibility assays, cell adhesion and differentiation. Results: The parameters of the newly fabricated materila were optimal for PCL/β-TCP scaffold fabrication. Composite surfaces showed higher hydrophilicity compared with the controls, and their surface roughness sharply was higher, possibly due to the presence of β-TCP. The Young's modulus of the composites was significantly higher than that of pristine PCL, indicating that the intrinsic strength of β-TCP is beneficial for enhancing the elastic modulus of the composite biomaterials. All novel composite biomaterials supported greater cellular growth and stronger osteoblastic differentiation compared with the PCL control. Conclusions: This project highlights the possibility to fabricat, through an FDM solvent-free approach, PCL/β-TCP scaffolds of up to 70 % concentrations of β-TCP. overcoming the current lmit of 60 % stated in the literature. The combination of 3D printing and customised biomaterials allowed production of highly personalised scaffolds with optimal mechanical and biological features resembling the natural structure and the composition of bone. This underlines the promise of such structures for innovative approaches for bone and periodontal regeneration.

Abstract Background Sustained drug delivery system (DDS) for clinically relevant osteosarcoma medications is a promising strategy for treatment. β-tricalcium phosphate (β-TCP) microbeads loaded with doxorubicin hydrochloride (DOX) and cis-diamminedichloroplatin (CDDP) anticancer drugs in a matrix of hydroxyapatite-keratin-polyvinyl alcohol composite matrix scaffolds (HAp-K-PVA) was developed as promising DDS. HAp, β-TCP, and K utilized for the development of DDS were resourced from avian eggshells and human hairs, respectively, and duly characterized before application. Methods The β-TCP/alginate microbeads were fabricated using droplet extrusion and ionotropic gelation, and integrated into secondary drug carrier HAp-K-PVA composite matrix, via freeze gelation. The physicochemical and thermal characterization of developed microbeads and matrix scaffolds was performed. Results When DOX and CDDP were co-loaded in DDS, a synergistic impact was observed after 30 days of continuous release, in contrast to the immediate outburst as seen with individual DOX and CDDP releases. Besides, the drug release from the microbeads only, the release with the HAp-K-PVA composite matrix scaffolds was observed slower. The controlled release, antibacterial effectiveness against the test pathogens and cell viability with osteoblast-like osteosarcoma (UTOS) cells indicated the therapeutic potential for the treatment of osteosarcoma in situ. The cell viability was observed for 24 h, which showed nearly 90% after 24 h for HAp-K-PVA composite matrix scaffolds, decreased for all the scaffold groups after 72 h, indicating the enhancement due to combined synergistic effect of the co-loaded drugs. Conclusion This study established a promising foundation for novel and sustainable biomaterials for osteosarcoma treatment. Further advancement holds the potential to enhance patient clinical outcomes and foster advancements in the field of regenerative medicine.

Abstract Suitable biomaterials with seed cells have promising potential to repair bone defects. However, bone marrow mesenchymal stem cells (BMSCs), one of the most common seed cells used in tissue engineering, cannot differentiate efficiently and accurately into functional osteoblasts. In view of this, a new tissue engineering technique combined with BMSCs and scaffolds is a major task for bone defect repair. Lentiviruses interfering with miR‐136‐5p or Smurf1 expression were transfected into BMSCs. The effects of miR‐136‐5p or Smurf1 on the osteogenic differentiation (OD) of BMSCs were evaluated by measuring alkaline phosphatase activity and calcium deposition. Then, the targeting relationship between miR‐136‐5p and Smurf1 was verified by bioinformatics website analysis and dual luciferase reporter assay. Then, a rabbit femoral condyle bone defect model was established. miR‐136‐5p/BMSCs/β‐TCP scaffold was implanted into the defect, and the repair of the bone defect was detected by Micro‐CT and HE staining. Elevating miR‐136‐5p‐3p or suppressing Smurf1 could stimulate OD of BMSCs. miR‐136‐5p negatively regulated Smurf1 expression. Overexpressing Smurf1 reduced the promoting effect of miR‐136‐5p on the OD of BMSCs. miR‐136‐5p/BMSCs/β‐TCP could strengthen bone density in the defected area and accelerate bone repair. SmurF1‐targeting miR‐136‐5p‐modified BMSCs combined with 3D‐printed β‐TCP scaffolds can strengthen osteogenic activity and alleviate bone defects.

Background: Sustained drug delivery system (DDS) for clinically relevant osteosarcoma medications is a promising strategy for treatment. β-tricalcium phosphate (β-TCP) microbeads loaded with doxorubicin hydrochloride (DOX) and cis-diamminedichloroplatin (CDDP) anticancer drugs in a matrix of hydroxyapatite-keratin-polyvinyl alcohol composite matrix scaffolds (HAp-K-PVA) was developed as promising DDS. HAp, β-TCP, and K utilized for the development of DDS were resourced from avian eggshells and human hairs, respectively, and duly characterized before application. Methods: The β-TCP/alginate microbeads were fabricated using droplet extrusion and ionotropic gelation, and integrated into secondary drug carrier HAp-K-PVA composite matrix, via freeze gelation. The physicochemical and thermal characterization of developed microbeads and matrix scaffolds was performed. Results: When DOX and CDDP were co-loaded in DDS, a synergistic impact was observed after 30 days of continuous release, in contrast to the immediate outburst as seen with individual DOX and CDDP releases. Besides, the drug release from the microbeads only, the release with the HAp-K-PVA composite matrix scaffolds was observed slower. The controlled release, antibacterial effectiveness against the test pathogens and cell viability with osteoblast-like osteosarcoma (UTOS) cells indicated the therapeutic potential for the treatment of osteosarcoma in situ. The cell viability was observed for 24 h, which showed nearly 90% after 24 h for HAp-K-PVA composite matrix scaffolds, decreased for all the scaffold groups after 72 h, indicating the enhancement due to combined synergistic effect of the co-loaded drugs. Conclusion: This study established a promising foundation for novel and sustainable biomaterials for osteosarcoma treatment. Further advancement holds the potential to enhance patient clinical outcomes and foster advancements in the field of regenerative medicine. [ABSTRACT FROM AUTHOR]

The aim of the study was to compare conventional sintering with additive manufacturing techniques for β-TCP bioceramics, focusing on mechanical properties and biocompatibility. A "critical" bone defect requires surgical intervention beyond simple stabilization. Autologous bone grafting is the gold standard treatment for such defects, but it has its limitations. Alloplastic bone grafting with synthetic materials is becoming increasingly popular. The use of bone graft substitutes has increased significantly, and current research has focused on optimizing these substitutes, whereas this study compares two existing manufacturing techniques and the resulting β-TCP implants. The 3D printed β-TCP hybrid structure implant was fabricated from two components, a column structure and a freeze foam, which were sintered together. The conventionally fabricated ceramics were fabricated by casting. Both scaffolds were characterized for porosity, mechanical properties, and biocompatibility. The hybrid structure had an overall porosity of 74.4 ± 0.5%. The microporous β-TCP implants had a porosity of 43.5 ± 2.4%, while the macroporous β-TCP implants had a porosity of 61.81%. Mechanical testing revealed that the hybrid structure had a compressive strength of 10.4 ± 6 MPa, which was significantly lower than the microporous β-TCP implants with 32.9 ± 8.7 MPa. Biocompatibility evaluations showed a steady increase in cell proliferation over time for all the β-TCP implants, with minimal cytotoxicity. This study provides a valuable insight into the potential of additive manufacturing for β-TCP bioceramics in the treatment of bone defects. [ABSTRACT FROM AUTHOR]

Bone tissue is a highly vascularized tissue. When constructing tissue‐engineered bone models, both the osteogenic and angiogenic capabilities of the construct should be carefully considered. However, fabricating a vascularized tissue‐engineered bone to promote vascular formation and bone generation, while simultaneously establishing nutrition channels to facilitate nutrient exchange within the constructs, remains a significant challenge. Triaxial bioprinting, which not only allows the independent encapsulation of different cell types while simultaneously forming nutrient channels, could potentially emerge as a strategy for fabricating vascularized tissue‐engineered bone. Moreover, bioinks should also be applied in combination to promote both osteogenesis and angiogenesis. In this study, employing triaxial bioprinting, we used a blend bioink of gelatin methacryloyl (GelMA), sodium alginate (Alg), and different concentrations of nano beta‐tricalcium phosphate (nano β‐TCP) encapsulated MC3T3‐E1 preosteoblasts as the outer layer, a mixed bioink of GelMA and Alg loaded with human umbilical vein endothelial cells (HUVEC) as the middle layer, and gelatin as a sacrificial material to form nutrient channels in the inner layer to fabricate vascularized bone constructs simulating the microenvironment for bone and vascular tissues. The results showed that the addition of nano β‐TCP could adjust the mechanical, swelling, and degradation properties of the constructs. Biological assessments revealed the cell viability of constructs containing different concentrations of nano β‐TCP was higher than 90% on day 7, The cell‐laden constructs containing 3% (w/v) nano β‐TCP exhibited better osteogenic (higher Alkaline phosphatase activity and larger Osteocalcin positive area) and angiogenic (the gradual increased CD31 positive area) potential. Therefore, using triaxial bioprinting technology and employing GelMA, Alg, and nano β‐TCP as bioink components could fabricate vascularized bone tissue constructs, offering a novel strategy for vascularized bone tissue engineering. [ABSTRACT FROM AUTHOR]

Suitable biomaterials with seed cells have promising potential to repair bone defects. However, bone marrow mesenchymal stem cells (BMSCs), one of the most common seed cells used in tissue engineering, cannot differentiate efficiently and accurately into functional osteoblasts. In view of this, a new tissue engineering technique combined with BMSCs and scaffolds is a major task for bone defect repair. Lentiviruses interfering with miR‐136‐5p or Smurf1 expression were transfected into BMSCs. The effects of miR‐136‐5p or Smurf1 on the osteogenic differentiation (OD) of BMSCs were evaluated by measuring alkaline phosphatase activity and calcium deposition. Then, the targeting relationship between miR‐136‐5p and Smurf1 was verified by bioinformatics website analysis and dual luciferase reporter assay. Then, a rabbit femoral condyle bone defect model was established. miR‐136‐5p/BMSCs/β‐TCP scaffold was implanted into the defect, and the repair of the bone defect was detected by Micro‐CT and HE staining. Elevating miR‐136‐5p‐3p or suppressing Smurf1 could stimulate OD of BMSCs. miR‐136‐5p negatively regulated Smurf1 expression. Overexpressing Smurf1 reduced the promoting effect of miR‐136‐5p on the OD of BMSCs. miR‐136‐5p/BMSCs/β‐TCP could strengthen bone density in the defected area and accelerate bone repair. SmurF1‐targeting miR‐136‐5p‐modified BMSCs combined with 3D‐printed β‐TCP scaffolds can strengthen osteogenic activity and alleviate bone defects. [ABSTRACT FROM AUTHOR]

Extrusion based 3-D printing has been extensively applied to create geometrically complex composite polymer-ceramic structures as bone tissue substitute. The rheological features of the formulated bioink that regulate the printability and resolution of the printed scaffolds, rely on physicochemical properties of ink components, mainly their composition and chemical structure. The aim of this study was to evaluate the effect of different content of 45S5 bioglass (BG) and β-tricalcium phosphate (β-TCP) nanoparticles on the rheological behavior of printing inks and final composite scaffolds based on polycaprolactone (PCL)/BG/β-TCP. Ceramic nano-powders were first characterized and the composite bioinks were prepared by mixing various ratios of BG and β-TCP powders into the 50 % w/v of PCL solution (β-TCP/BG: 70/30, 50/50, 30/70, and 10/90 w/w %). All formulated inks showed a thixotropic behavior and viscosity significantly increased by applying higher fraction of BG. Interestingly highly loaded β-TCP ink (β-TCP/BG: 70/30) revealed a rubbery nature with high surface tension which reduced final scaffolds resolution. All printed scaffolds possessed highly porous structure with interconnected pores. However, porosity percentage and shape stability improved by increasing BG content which was accompanied with lower mechanical strength and superior biodegradation and bioactivity of scaffolds. The biological performance of the printed scaffolds was evaluated using osteoblast cell line MG-63. MTT assay and cell attachment observation by SEM confirmed that printed scaffolds are well biocompatible and properly support cell colonization and proliferation. In overall, besides more appropriate materialistic properties, scaffolds with β-TCP/BG: 30/70 composition provided the most favorable microenvironment for cell colonization and growth.

Introductionβ-TCP ceramics are bone replacement materials that have recently been tested as a drug delivery system that can potentially be applied to endogenous substances like growth factors found in blood platelets to facilitate positive attributes.MethodsIn this work, we used flow chamber loading to load β-TCP dowels with blood suspensions of platelet-rich plasma (PRP), platelet-poor plasma (PPP), or buffy coat (BC) character. PRP and BC platelet counts were adjusted to the same level by dilution. Concentrations of TGF-β1, PDGF-AB, and IGF-1 from dowel-surrounding culture medium were subsequently determined using ELISA over 5 days. The influence of alginate was additionally tested to modify the release.ResultsConcentrations of TGF-β1 and PDGF-AB increased and conclusively showed a release from platelets in PRP and BC compared to PPP. The alginate coating reduced the PDGF-AB release but did not reduce TGF-β1 and instead even increased TGF-β1 in the BC samples. IGF-1 concentrations were highest in PPP, suggesting circulating levels rather than platelet release as the driving factor. Alginate samples tended to have lower IGF-1 concentrations, but the difference was not shown to be significant.DiscussionThe release of growth factors from different blood suspensions was successfully demonstrated for β-TCP as a drug delivery system with release patterns that correspond to PRP activation after Ca2+-triggered activation. The release pattern was partially modified by alginate coating.

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

Abstract β-TCP ceramics are versatile bone substitute materials and show many interactions with cells of the monocyte-macrophage-lineage. The possibility of monocytes entering microporous β-TCP ceramics has however not yet been researched. In this study, we used a model approach to investigate whether monocytes might enter β-TCP, providing a possible explanation for the origin of CD68-positive osteoclast-like giant cells found in earlier works. We used flow chambers to unidirectionally load BC, PRP, or PPP into slice models of either 2 mm or 6 mm β-TCP. Immunofluorescence for CD68 and live/dead staining was performed after the loading process. Our results show that monocytes were present in a relevant number of PRP and BC slices representing the inside of our 2 mm slice model and also present on the actual inside of our 6 mm model. For PPP, monocytes were not found beyond the surface in either model. Our results indicate the possibility of a new and so far neglected constituent in β-TCP degradation, perhaps causing the process of ceramic degradation also starting from inside the ceramics as opposed to the current understanding. We also demonstrated flow chambers as a possible new in vitro model for interactions between blood and β-TCP.

Abstract Fluorescence analysis of β-TCP ceramics is often used to describe cells found on said ceramics. However, we found, to our knowledge, so far undescribed artifacts which might sometimes be hard to differentiate from cells due to shape and fluorescence behavior. We tried prolonged ultrasound washing as well as Technovit 9100 fixation to reduce these artifacts. While untreated dowels showed no reduction in artifacts no matter the further treatment, Technovit fixation reduced the artifacts with even further reduction achieved by mechanical cleaning. As a consequence, scientists working with these dowels and likely even other types should try to avoid creating false positive results by considering the existence of these artifacts, checking additional filters for unusual fluorescence and by reducing them by using Technovit fixation when possible.

Large segmental bone defects are commonly operated with autologous bone grafting, which has limited bone sources and poses additional surgical risks. In this study, we fabricated poly(lactide-co-glycolic acid) (PLGA)/β-tricalcium phosphate (β-TCP) composite membranes by electrostatic spinning and further promoted osteogenesis by regulating the release of β-TCP in the hope of replacing autologous bone grafts in the clinical practice. The addition of β-TCP improved the mechanical strength of PLGA by 2.55 times. Moreover, β-TCP could accelerate the degradation of PLGA and neutralize the negative effects of acidification of the microenvironment caused by PLGA degradation. In vitro experiments revealed that PLGA/TCP10 membranes are biocompatible and the released β-TCP can modulate the activity of osteoblasts by enhancing the calcium ions concentration in the damaged area and regulating the pH of the local microenvironment. Simultaneously, an increase in β-TCP can moderate the lactate content of the local microenvironment, synergistically enhancing osteogenesis by promoting the tube-forming effect of human umbilical vein endothelial cells. Therefore, it is potential to utilize PLGA/TCP bioactive membranes to modulate the microenvironment at the site of bone defects to promote bone regeneration.

β-TCP ceramics are versatile bone substitute materials and show many interactions with cells of the monocyte-macrophage-lineage. The possibility of monocytes entering microporous β-TCP ceramics has however not yet been researched. In this study, we used a model approach to investigate whether monocytes might enter β-TCP, providing a possible explanation for the origin of CD68-positive osteoclast-like giant cells found in earlier works. We used flow chambers to unidirectionally load BC, PRP, or PPP into slice models of either 2 mm or 6 mm β-TCP. Immunofluorescence for CD68 and live/dead staining was performed after the loading process. Our results show that monocytes were present in a relevant number of PRP and BC slices representing the inside of our 2 mm slice model and also present on the actual inside of our 6 mm model. For PPP, monocytes were not found beyond the surface in either model. Our results indicate the possibility of a new and so far neglected constituent in β-TCP degradation, perhaps causing the process of ceramic degradation also starting from inside the ceramics as opposed to the current understanding. We also demonstrated flow chambers as a possible new in vitro model for interactions between blood and β-TCP. [ABSTRACT FROM AUTHOR]

Background: Beta-tricalcium phosphate (β-TCP) is a biocompatible ceramic material widely used in the field of oral regeneration. Due to its excellent biological and mechanical properties, it is increasingly utilized for alveolar ridge augmentation or guided bone regeneration (GBR). With recent advances in computer-aided design and manufacturing (CAD/CAM), β-TCP can now be used in the form of digitally designed patient-specific scaffolds for customized bone regeneration (CBR) of advanced defects in a two-stage implant therapy concept. In this case report following the CARE case report guidelines, we present a novel application of a patient-specific β-TCP scaffold in pre-implant mandibular alveolar ridge augmentation. Case presentation: A 63-year-old female patient with significant horizontal bone loss in the posterior mandible was treated with a custom β-TCP scaffold in the context of a two-stage backward-planned implant therapy. Cone-beam computed tomography nine months after augmentation showed successful integration of the scaffold into the surrounding bone, allowing implant placement. Follow-up until two years after initial surgery showed excellent oral and peri-implant health. Conclusions: This case highlights the potential of patient-specific β-TCP scaffolds for alveolar ridge augmentation and their advantage over traditional techniques, including avoidance of xeno-, allo-, and autografts. The results provide encouraging evidence for their use in clinical practice. Patient-specific β-TCP scaffolds may be a promising alternative for clinicians seeking to provide their patients with safe, predictable, and effective alveolar ridge augmentation results in customized bone regeneration procedures. [ABSTRACT FROM AUTHOR]

Fluorescence analysis of β-TCP ceramics is often used to describe cells found on said ceramics. However, we found, to our knowledge, so far undescribed artifacts which might sometimes be hard to differentiate from cells due to shape and fluorescence behavior. We tried prolonged ultrasound washing as well as Technovit 9100 fixation to reduce these artifacts. While untreated dowels showed no reduction in artifacts no matter the further treatment, Technovit fixation reduced the artifacts with even further reduction achieved by mechanical cleaning. As a consequence, scientists working with these dowels and likely even other types should try to avoid creating false positive results by considering the existence of these artifacts, checking additional filters for unusual fluorescence and by reducing them by using Technovit fixation when possible. [ABSTRACT FROM AUTHOR]

Osteochondral defects present significant challenges for effective tissue regeneration due to the complex composition of bone and cartilage. To address this challenge, this study presents the fabrication of hierarchical scaffolds combining chitosan/β-tricalcium phosphate (β-TCP) to simulate a bone-like layer, interconnected with a silk fibroin layer to mimic cartilage, thus replicating the cartilage-like layer to mimic the native osteochondral tissue architecture. The scaffolds were produced by freeze-drying and then crosslinking with genipin. They have a crosslinking degree of up to 24%, which promotes a structural rearrangement and improved connection between the different layers. Micro-CT analysis demonstrated that the structures have distinct porosity values on their top layer (up to 84%), interface (up to 65%), and bottom layer (up to 77%) and are dependent on the concentration of β-tricalcium phosphate used. Both layers were confirmed to be clearly defined by the distribution of the components throughout the constructs, showing adequate mechanical properties for biomedical use. The scaffolds exhibited lower weight loss (up to 7%, 15 days) after enzymatic degradation due to the combined effects of genipin crosslinking and β-TCP incorporation. In vitro studies showed that the constructs supported ATDC5 chondrocyte-like cells and MC3T3 osteoblast-like cells in duo culture conditions, providing a suitable environment for cell adhesion and proliferation for up to 14 days. Overall, the physicochemical properties and biological results of the developed chitosan/β-tricalcium phosphate/silk fibroin bilayered scaffolds suggest that they may be potential candidates for osteochondral tissue strategies. [ABSTRACT FROM AUTHOR]

Well-defined, faintly radiopaque lesions are occasionally observed in the antrum of the maxillary sinus in asymptomatic patients during maxillary sinus floor elevation. These lesions are treated as antral pseudocysts (AP) based on the clinical diagnosis in some cases, and maxillary sinus floor elevation is performed without enucleating these lesions. However, further surgery is required after implant placement if the lesion is a mucocele, odontogenic cyst, or tumour. This comprehensive clinical review aimed to identify an appropriate approach for maxillary sinus floor elevation in patients with well-defined, faintly radiopaque lesions in the antrum based on our clinical experience. [ABSTRACT FROM AUTHOR]

In this study, we successfully prepared porous composite microspheres composed of hydroxyapatite (HAp), di-calcium phosphate di-hydrated (DCPD), and chitosan through the hydrothermal method. The chitosan played a crucial role as a chelating agent to facilitate the growth of related calcium phosphates. The synthesized porous composite microspheres exhibit a specific surface area of 38.16 m2/g and a pore volume of 0.24 cm3/g, with the pore size ranging from 4 to 100 nm. Given the unique properties of chitosan and the exceptional porosity of these composite microspheres, they may serve as carriers for pharmaceuticals. After being annealed, the chitosan transforms into a condensed form and the DCPD transforms into Ca2P2O7 at 300 °C. Then, the Ca2P2O7 initially combines with HAp to transform into β tricalcium phosphate (β-TCP) at 500 °C where the chitosan is also completely combusted. Finally, the microspheres are composed of Ca2P2O7, β-TCP, and HAp, also making them suitable for applications such as injectable bone graft materials. [ABSTRACT FROM AUTHOR]

Although β-TCP bioceramics possess favorable biocompatibility and bioactivity, their inherent brittleness restricts further applications. In this study, we aimed to enhance the mechanical performance and biocompatibility of β-TCP by incorporating 15% Akermanite (AK) into the structure. The fabrication process involved the use of digital light processing (DLP) technology to fabricate ceramic green bodies, followed by high-temperature debinding and sintering to obtain the ceramic scaffold. Subsequently, we employed an in-situ growth technique to create micro/nano surface topography on the scaffolds, facilitating synergistic regulation of cell behavior in conjunction with the controlled release of bioactive agents. Scanning electron microscopy (SEM) revealed that the addition of AK enlarged the grain size and reduced the number of micropores in the composite scaffold. Furthermore, after the in-situ growth treatment, a significant increase in micro/nano surface features was observed. Mechanical testing demonstrated that the incorporation of AK effectively improved the mechanical properties of the composite scaffold, resulting in an increase in strength of approximately 20%. Cell experiments indicated that AK supplementation further enhanced the material's cell compatibility, and the presence of micro/nano structures effectively promoted cell adhesion, proliferation, and expression of osteogenic genes. Consequently, we propose a strategy for fabricating porous bioceramics that stimulate bone growth, exhibit high strength, and ameliorate the degradation microenvironment. This approach opens up promising avenues for future applications in bone tissue engineering. [ABSTRACT FROM AUTHOR]

A new series of Sr-based phosphates, Sr9−xMnxEu(PO4)7, were synthesized using the high-temperature solid-state method in air. It was found that these compounds have the same structure as strontiowhitlockite, which is a β-Ca3(PO4)2 (or β-TCP) structure. The concentration of Mn2+ ions required to form a pure strontiowhitlockite phase was determined. An unusual partial reduction of Eu3+ to Eu2+ in air was observed and confirmed by photoluminescence (PL) and electron spin resonance (ESR) spectra measurements. The PL spectra recorded under 370 nm excitation showed transitions of both 4f5d–4f Eu2+ and 4f–4f Eu3+. The total integral intensity of the PL spectra, monitored at 395 nm, decreased with increasing Mn2+ concentration due to quenching effect of Eu3+ by the Mn2+ levels. The temperature dependence of Eu2+ photoluminescence in a Sr9−xMnxEu(PO4)7 host was investigated. The conditions for the reduction of Eu3+ to Eu2+ in air were discussed. [ABSTRACT FROM AUTHOR]

Calcium phosphate cement (CPC) is generally used for bone repair and augmentation. Poloxamers are tri‐block copolymers that are used as surfactants but have applications in drug and antibiotic delivery. However, their biological effects on bone regeneration systems remain unelucidated. Here, we aimed to understand how supplementing the prototype CPC with poloxamer would impact cellular activity and its function as a bone‐grafting material. A novel CPC, modified beta‐tricalcium phosphate (mβ‐TCP) powder, was developed through a planetary ball‐milling process using a beta‐tricalcium phosphate (β‐TCP). The mβ‐TCP dissolves rapidly and accelerates hydroxyapatite precipitation; successfully shortening the cement setting time and enhancing the strength. Furthermore, the addition of poloxamer 407 to mβ‐TCP could reduce the risk of leakage from bone defects and improve fracture toughness while maintaining mechanical properties. In this study, the poloxamer addition effects (0.05 and 0.1 g/mL) on the cellular activities of MC3T3‐E1 cells cultured in vitro were investigated. The cell viability of mβ‐TCP containing poloxamer 407 was similar to that of mβ‐TCP. All specimens showed effective cell attachment and healthy polygonal extension of the cytoplasm firmly attached to hydroxyapatite (HA) crystals. Therefore, even with the addition of poloxamer to mβ‐TCP, it does not have a negative effect to osteoblast growth. These data demonstrated that the addition of poloxamer 407 to mβ‐TCP might be considered a potential therapeutic application for the repair and regeneration of bone defects. [ABSTRACT FROM AUTHOR]

We investigated the effectiveness and safety of a new composite‐based biodegradable anterior cervical plate/screw (ACPS) system for the anterior cervical discectomy and fusion (ACDF) fixation. A biocomposite in combination with 30 wt% β‐tricalcium phosphate (β‐TCP; a biodegradable ceramic having osteoconductive ability) and 70 wt% poly‐l/d‐lactide copolymer (PLDLA; a biodegradable polymer) was developed and used in the ACPS device, comprising one plate and four screws for fixation. Based on a literature review, a clinically required period of performance maintenance was set as 16 weeks, and to verify the performance for a period of 16 weeks or more, the test was conducted for 26 weeks. Following ISO 13781:2017 testing protocols, an in vitro degradation test was performed to verify the performance and evaluate the decomposition characteristics of the biodegradable ACPS system. Using an animal model as a preclinical investigation, the prepared ACPS device was implanted into five mongrel dogs weighing over 30 kg to evaluate the detachment prevention effect of the ACPS system on polyether ether ketone (PEEK) cage after ACDF. By week 26, the molecular weight was decreased by 45.35% for the plate and 52.56% for the screw; the bending strength of the plate was decreased by approximately 26.2% when compared with the initial stage. The torsional yield strength and pullout strength of the screw was increased by 52.31% and 5.3%, respectively by week 2 and then subsequently decreased until week 26. No detachment or dislocation of the inserted PEEK cage was observed for 26 weeks in vivo study. These findings recommend that the ACPS system might be a promising biodegradable tool for the fixation of interbody implants and supporting the fusion in an ACDF model. Furthermore, additional clinical trials are planned for the future. [ABSTRACT FROM AUTHOR]

Various efforts have been made to develop antibacterial biomaterials capable of also sustaining bone remodulation to be used as bone substitutes and reduce patient infection rates and related costs. In this work, beta-tricalcium phosphate (β-TCP) was chosen due to its known biocompatibility and use as a bone substitute. Metal dopants were incorporated into the crystal structure of the β-TCP, and disks were produced from this material. Magnesium and strontium, as well as copper and silver, were chosen as dopants to improve the osteogenic and antibacterial properties, respectively. The surface of the β-TCP samples was further modified using a femtosecond laser system. Grid and line patterns were produced on the plates' surface via laser ablation, creating grooves with depths lower than 20 μm and widths between 20 and 40 μm. Raman and FTIR analysis confirmed that laser ablation did not result in the degradation or phase change of the materials, making it suitable for surface patterning. Laser ablation resulted in increased hydrophilicity of the materials, as the control samples (non-ablated samples) have WCA values ranging from 70° to 93° and become, upon laser ablation, superwicking surfaces. Confocal measurements show an increase in specific surface area of 50% to 200% compared to the control. Overall, the results indicate the potential of laser ablation to improve the surface characteristics of β-TCP, which may lead to an improvement in the antibacterial and osteogenic properties of the produced materials. [ABSTRACT FROM AUTHOR]

A variety of techniques have been used for treating avascular necrosis of the femoral head (ANFH), but have frequently failed. In this study, we proposed a β-TCP system for the treatment of ANFH by boosting revascularization and bone regeneration. The angio-conductive properties and concurrent osteogenesis of the highly interconnected porous β-TCP scaffold were revealed and quantified through an in vivo model that simulated the ischemic environment of ANFH. Mechanical test and finite element analysis showed that the mechanical loss caused by tissue necrosis and surgery was immediately partially compensated after implantation, and the strength of the operated femoral head was adaptively increased and eventually returned to normal bone, along with continuous material degradation and bone regeneration. For translational application, we further conducted a multi-center open-label clinical trial to assess the efficacy of the β-TCP system in treating ANFH. Two hundred fourteen patients with 246 hips were enrolled for evaluation, and 82.1% of the operated hips survived at a 42.79-month median follow-up. The imaging results, hip function, and pain scores were dramatically improved compared to preoperative levels. ARCO stage Ⅱ disease outperformed stage Ⅲ in terms of clinical effectiveness. Thus, bio-adaptive reconstruction using the β-TCP system is a promising hip-preserving strategy for the treatment of ANFH.

The aim of the study was to compare conventional sintering with additive manufacturing techniques for β-TCP bioceramics, focusing on mechanical properties and biocompatibility. A “critical” bone defect requires surgical intervention beyond simple stabilization. Autologous bone grafting is the gold standard treatment for such defects, but it has its limitations. Alloplastic bone grafting with synthetic materials is becoming increasingly popular. The use of bone graft substitutes has increased significantly, and current research has focused on optimizing these substitutes, whereas this study compares two existing manufacturing techniques and the resulting β-TCP implants. The 3D printed β-TCP hybrid structure implant was fabricated from two components, a column structure and a freeze foam, which were sintered together. The conventionally fabricated ceramics were fabricated by casting. Both scaffolds were characterized for porosity, mechanical properties, and biocompatibility. The hybrid structure had an overall porosity of 74.4 ± 0.5%. The microporous β-TCP implants had a porosity of 43.5 ± 2.4%, while the macroporous β-TCP implants had a porosity of 61.81%. Mechanical testing revealed that the hybrid structure had a compressive strength of 10.4 ± 6 MPa, which was significantly lower than the microporous β-TCP implants with 32.9 ± 8.7 MPa. Biocompatibility evaluations showed a steady increase in cell proliferation over time for all the β-TCP implants, with minimal cytotoxicity. This study provides a valuable insight into the potential of additive manufacturing for β-TCP bioceramics in the treatment of bone defects.

A three-stage solid state synthesis assisted by thermodynamic modelling was developed to prepare highly pure (>99 %) beta tricalcium phosphate (β-TCP) powder. The optimal synthesis temperature was experimentally determined to be 1000 °C in good agreement with the theoretical calculations. The synthesis design described here has substantially improved the product quality and eliminated the presence of secondary phosphate phases compared to one- and two-stage methods investigated in this work. A comprehensive characterization of the material’s structural, vibrational, and morphological characteristics was conducted. Rietveld refinement of the X-ray diffraction data confirmed the high purity of the samples. The crystal structure of the prepared β-TCP was determined and the refined unit cell parameters agreed well with the reference values. From infrared and Raman spectral analyses, the characteristics of β-TCP were observed and discussed in details. Furthermore, the morphology and elemental composition of the products were examined and found to be homogenous and impurity free. The reproducibility of the material was scrutinized and showed no significant data variations. Using our three-stage synthesis method, it is possible to produce β-TCP powder of high purity with consistent repeatability.

BACKGROUND: While autografts to date remain the "gold standard" for bone void fillers, synthetic bone grafts have garnered attention due to their favorable advantages such as ability to be tailored in terms of their physical and chemical properties. Bioactive glass (BG), an inorganic material, has the capacity to form a strong bond with bone by forming a bone-like apatite surface, enhancing osteogenesis. Coupled with additive manufacturing (3D printing) it is possible to maximize bone regenerative properties of the BG. OBJECTIVE: The objective of this study was to synthesize and characterize 3D printed mesoporous bioactive glass (MBG), BG 45S5, and compare to β-Tricalcium phosphate (β-TCP) based scaffolds; test cell viability and osteogenic differentiation on human osteoprogenitor cells in vitro. METHODS: MBG, BG 45S5, and β-TCP were fabricated into colloidal gel suspensions, tested with a rheometer, and manufactured into scaffolds using a 3D direct-write micro-printer. The materials were characterized in terms of microstructure and composition with Thermogravimetric Analyzer/Differential Scanning Calorimeter (TGA/DSC), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Micro-Computed Tomography (μ-CT), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS), and Mattauch–Herzog-Inductively Coupled Plasma-Mass Spectrometry (MH-ICP-MS). RESULTS: Scaffolds were tested for cell proliferation and osteogenic differentiation using human osteoprogenitor cells. Osteogenic media was used for differentiation, and immunocytochemistry for osteogenic markers Runx-2, Collagen-I, and Osteocalcin. The cell viability results after 7 days of culture yielded significantly higher (p < 0.05) results in β-TCP scaffolds compared to BG 45S5 and MBG groups. CONCLUSION: All materials expressed osteogenic markers after 21 days of culture in expansion and osteogenic media. [ABSTRACT FROM AUTHOR]

This study investigated a novel method for artificial synthesis of β-tricalcium phosphate (β-TCP). The binder of the phosphate-bonded investment was replaced with calcium oxide instead of magnesium oxide and sintered in an electric furnace. The water/powder mixing ratio for hardening was determined using preliminary experiments. Thermal analysis was performed to check the thermal behavior of the sample tested. In addition, the fired sample was analyzed using an X-ray diffraction apparatus to identify the compounds after sintering. The hardened sample exhibited multiple compounds, including unreacted components, post which, new compounds were generated by heating. Peaks of calcium pyrophosphate and β-TCP were confirmed at 800ºC and 1,300ºC, respectively. β-TCP could be easily synthesized within the limited study by sintering at 1,300ºC both monoammonium phosphate and calcium oxide. Experimental results suggest that β-TCP can be easily synthesized by simulating the conventional dental casting process. [ABSTRACT FROM AUTHOR]

For the treatment of bone defects, biodegradable, compressive biomaterials are needed as replacements that degrade as the bone regenerates. The problem with existing materials has either been their insufficient mechanical strength or the excessive differences in their elastic modulus, leading to stress shielding and eventual failure. In this study, the compressive strength of CPC ceramics (with a layer thickness of more than 12 layers) was compared with sintered β-TCP ceramics. It was assumed that as the number of layers increased, the mechanical strength of 3D-printed scaffolds would increase toward the value of sintered ceramics. In addition, the influence of the needle inner diameter on the mechanical strength was investigated. Circular scaffolds with 20, 25, 30, and 45 layers were 3D printed using a 3D bioplotter, solidified in a water-saturated atmosphere for 3 days, and then tested for compressive strength together with a β-TCP sintered ceramic using a Zwick universal testing machine. The 3D-printed scaffolds had a compressive strength of 41.56 ± 7.12 MPa, which was significantly higher than that of the sintered ceramic (24.16 ± 4.44 MPa). The 3D-printed scaffolds with round geometry reached or exceeded the upper limit of the compressive strength of cancellous bone toward substantia compacta. In addition, CPC scaffolds exhibited more bone-like compressibility than the comparable β-TCP sintered ceramic, demonstrating that the mechanical properties of CPC scaffolds are more similar to bone than sintered β-TCP ceramics. [ABSTRACT FROM AUTHOR]

Background: Microfracture (MF) is frequently performed as a first-line treatment for articular cartilage defects. Although good clinical outcomes are often obtained in the short term, poor clinical outcomes sometimes occur because of subchondral bone deterioration. The condition of the subchondral bone treated with MF may affect the repair of the osteochondral unit. Purpose: To analyze histological findings of the osteochondral unit after performing MF on subchondral bone in different states—normal, absorption, and sclerosis—in a rat model. Study Design: Controlled laboratory study. Methods: Full-thickness cartilage defects (5.0 × 3.0 mm) were created in the weightbearing area of the medial femoral condyle in both knees of 47 Sprague-Dawley rats. Five MF holes were created within the cartilage defect using a 0.55-mm needle to a depth of 1 mm at 0 weeks (normal group), 2 weeks (absorption group), and 4 weeks (sclerosis group) after the cartilage defect was created. In the left knee, MF holes were filled with β-tricalcium phosphate (β-TCP). At 2 and 4 weeks after MF, knee joints were harvested and histologically analyzed. Results: MF holes were enlarged at 2 weeks and further enlarged at 4 weeks in all groups. In the absorption group, osteoclast accumulation around the MF holes and cyst formation were observed. The trabecular bone surrounding the MF holes was thickened in the sclerosis group. The diameter of the MF hole was largest in the absorption group at 2 and 4 weeks after MF compared with the other groups. No subchondral bone cysts were observed after β-TCP implantation. Pineda scores in all groups were significantly better with β-TCP implantation than without β-TCP implantation at 2 and 4 weeks. Conclusion: MF for subchondral bone with bone absorption induced enlargement of the MF holes, cyst formation, and delay of cartilage defect coverage. Implantation of β-TCP into the MF holes enhanced remodeling of the MF holes and improved repair of the osteochondral unit compared with MF only. Therefore, the condition of the subchondral bone treated with MF affects repair of the osteochondral unit in a cartilage defect. [ABSTRACT FROM AUTHOR]

The large variability of biological responses to β-TCP implants reported in the literature could possibly be related to subtle differences in the β-TCP crystal structure. The structure contains one partially occupied site Ca(4). In order to better understand the ordering of this site, 12 pairs of unit cells with different Ca(4) site occupancies were combined in different checkerboard patterns with an average occupancy of 3. Atomistic simulations were conducted to identify the lowest energy configurations. The previously published low energy configuration is not the most stable one when considering a larger supercell. Plotting the 662 simulation outputs by lattice parameters a or c versus relative lattice energy revealed clusters of high density which are composed of configurations with predominant motifs of Ca(4) occupancy. The tools introduced in this study can be applied in future simulation studies to better explain the Ca(4) site occupancy in the β-TCP crystal structure. [ABSTRACT FROM AUTHOR]

β‐tricalcium phosphate (β‐TCP, β‐Ca3(PO4)2) is an attractive biomaterial for bone repair applications. However, its sintering and mechanical properties are limited by a problematic phase transition to α‐TCP. Cationic doping of β‐TCP is able to postpone the formation of α‐TCP allowing higher sintering temperatures and better mechanical properties. The co‐doping of β‐TCP with Mg2+ and Sr2+ has already been studied in detail, but the addition of antibacterial cations (Ag+ and Cu2+) on the Mg–Sr β‐TCP co‐doped composition remains unexplored. Thus, two co‐doped β‐TCP compositions were realized by aqueous precipitation technique without any secondary phase and compared with undoped β‐TCP: Mg–Sr (2.0–2.0 mol%) and Mg–Sr–Ag–Cu (2.0–2.0–0.1–0.1 mol%). Differential thermal analysis and dilatometry analyses showed a slight decrease of the β‐TCP → α‐TCP phase transition temperature for the Mg–Sr–Ag–Cu (2.0–2.0–0.1–0.1% mol) composition as compared to the Mg–Sr (2.0–2.0 mol%). However, both exhibited much higher transition temperatures than undoped β‐TCP. The addition of Ag+ and Cu2+ slightly reduces the grain size after sintering compared to the Mg–Sr (2.0–2.0 mol%) and the undoped compositions. The co‐doped compositions also exhibited improved mechanical properties, specifically a higher Vickers hardness and elastic modulus. Finally, cell proliferation assays showed that the presence of dopants, even Ag+ and Cu2+, does not affect the survival and proliferation of cells. Thus, the use of Mg2+, Sr2+, Ag+, and Cu2+ co‐doped β‐TCP could be very promising for biomedical applications due to the improvements of these dopants on the thermal stability and mechanical and biological properties. [ABSTRACT FROM AUTHOR]

The aim was to formulate an experimental adhesive (EA) and added nanoparticles (NPs) of beta‐tricalcium phosphate (β‐TCP) to see the impact on pushout bond strength (PBS) and other mechanical properties. Three adhesives were prepared, including EA (control, without β‐TCP NPs), 2.5%‐β‐TCP NPs containing adhesive (2.5%‐NPA), and 5% β‐TCP NPs containing adhesive (5%‐NPA). For the characterization of the NPs, scanning electron microscopy (SEM) and energy dispersive X‐ray (EDX) spectroscopy was accomplished. For the adhesive's characterization, rheological assessment, and degree of conversion (DC) analysis were performed. PBS of these adhesives against resin fiber post to root dentin, interfacial failure categories, and resin dentin interface analysis were also assessed. The β‐TCP NPs were seen as agglomerated asymmetrical particles on SEM. These NPs were composed primarily of calcium (Ca), and phosphorus (P). Rheological evaluation of the adhesive's showed a drop in the viscosity of all adhesives at greater angular frequencies. The greatest DC was detected for the EA group (67.54 ± 7.9) followed by 2.5%‐NPA group (45.32 ± 5.1), whereas the lowest DC values were seen for the 5%‐NPA group (38.97 ± 6.5). Concerning PBS, the 2.5%‐NPA revealed the highest values at the coronal (12.81 ± 3.0) and middle (8.50 ± 2.3) sections, whereas, for the apical section, the highest PBS values were seen for the 5%‐NPA (4.9 ± 1.6). Most of the failures for all adhesive groups were seen at the adhesive‐dentin interface (cohesive type failures) for all root segments (coronal, middle, and apical). The resin‐dentin interface analysis verified hybrid layer and resin tag formation for all adhesives, but the presence of dispersed β‐TCP NPs was only seen in the two NP‐reinforced adhesives. The adding of β‐TCP NPs in the adhesive could be beneficial as it could improve its PBS. Suitable rheological properties and dentin interaction were also observed for NP‐reinforced adhesives. A reduced DC was seen for both β‐TCP NP‐containing adhesives as compared to the EA. Research Highlights: Experimental adhesives were reinforced with beta‐tricalcium phosphate (β‐TCP) nanocrystals.The β‐TCP NPs were seen as agglomerated asymmetrical particles on SEM. These NPs were composed primarily of calcium (Ca), and phosphorus (P).β‐TCP adhesives demonstrated superior pushout bond strength and a drop in the adhesive viscosity at greater angular frequencies compared to control adhesive.The greatest DC was detected for the EA group followed by 2.5%‐ β‐TCP group, whereas the lowest DC values were for the 5%‐ β‐TCP group. [ABSTRACT FROM AUTHOR]

Pure zinc has good biocompatibility and moderate degradation rate, but its mechanical properties are not ideal, which limits its biomedical applications. In view of the poor mechanical properties of zinc and its alloys, high-energy ball milling and spark plasma sintering techniques were used to prepare the alloy with core-shell structure Zn-10Mg-xβ-TCP (x=0,1,3,5) composites, β-TCP was selected as the reinforcing phase to improve the mechanical and corrosion properties of pure zinc. The microstructure, mechanical properties, and corrosion properties of Zn-10Mg-xβ-TCP (x=0,1,3,5) composite materials were investigated. The results show that all samples are relatively dense at 95% or above. The micro/nano-mechanical hardness of Zn-10Mg-1β-TCP is significantly higher than that of other samples, reaching 4.008 GPa; compressive strength and bending strength are 397 MPa and 92 MPa, respectively, and elongation is 6.5%, This is due to the small addition of β-TCP which produces dispersion strengthening and dislocation strengthening. In the electrochemical experiment, the corrosion current of Zn-10Mg-1β-TCP is not much different from that of zinc-magnesium alloy, which is significantly higher than that of other samples; in the long-term immersion experiment, the average corrosion current of sample Zn-10Mg-1β-TCP is the largest and meets the degradation rate requirements of implant material.

The importance of facile and reliable route for preparing pure beta-tricalcium phosphate (β-TCP) is immense for bone grafting application. In addition to compositional purity, repercussions related with control over development of porosity, i.e. shaping, are even greater. In this study, we considered two facile synthesis paths from aqueous solutions of calcium nitrate and diammonium hydrogenphosphate for preparation of β-TCP based powder; (I) controlled approach; a slow calcium deficient hydroxyapatite (CDHA) precipitation method with controlled pH, and (II) fast approach; a rapid CDHA precipitation, followed by calcination to obtain the β-TCP based form. After synthesis, we experimentally optimised the parameters for the production of ceramic templates with various morphology and microstructure through: (I) 3D printing, and (II) foam replication templating. Regarding the synthesis, X-ray diffraction (XRD) confirmed that the slow precipitation method yields pure β-TCP after calcination, while for the fast method, β-TCP in mixture with minor β-CPP (beta-calcium pyrophosphate) quantities was obtained. For both approaches, hydroxyapatite (HA) was not observed even in traces. The prepared porous ceramic bodies were broadly characterized through their total porosity (Archimedes' method), microporosity and specific surface (adsorption-desorption isotherms) and morphology by scanning electron microscopy (SEM). Characterisations give rise to a reliable synthetic route for preparing of highly porous monophasic β-TCP bodies. The course of shaping and porosity development of β-TCP bodies was meticulously considered. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the osteogenic and antimicrobial effect of bioactive glass S53P4 incorporated into β-tricalcium phosphate (β-TCP) scaffolds in vitro and the bone neoformation in vivo. β-TCP and β-TCP/S53P4 scaffolds were prepared by the gel casting method. Samples were morphologically and physically characterized through X-ray diffraction (XRD) and scanning electron microscope (SEM). In vitro tests were performed using MG63 cells. American Type Culture Collection reference strains were used to determine the scaffold's antimicrobial potential. Defects were created in the tibia of New Zealand rabbits and filled with experimental scaffolds. The incorporation of S53P4 bioglass promotes significant changes in the crystalline phases formed and in the morphology of the surface of the scaffolds. The β-TCP/S53P4 scaffolds did not demonstrate an in vitro cytotoxic effect, presented similar alkaline phosphatase activity, and induced a significantly higher protein amount when compared to β-TCP. The expression of Itg β1 in the β-TCP scaffold was higher than in the β-TCP/S53P4, and there was higher expression of Col-1 in the β-TCP/S53P4 group. Higher bone formation and antimicrobial activity were observed in the β-TCP/S53P4 group. The results confirm the osteogenic capacity of β-TCP ceramics and suggest that, after bioactive glass S53P4 incorporation, it can prevent microbial infections, demonstrating to be an excellent biomaterial for application in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Frequently, sinus augmentation is required when replacing failing or missing molars in the maxilla due to loss of alveolar bone related to periodontal disease, pneumatization of the sinus or a combination of the two factors. Various materials have been advocated and utilized; these fall into the categories of allograft, xenograft and synthetic materials. This article shall discuss a study of 10 cases with a 2-year follow-up utilizing a novel synthetic graft material used for sinus augmentation either simultaneously with implant placement or in preparation for sinus augmentation and implant placement in the posterior maxilla. The results of the 10 cases in the study found consistent results over the 2-year study period with maintenance of the alveolar height at the maxillary sinus. A lack of complications or failures in the study group demonstrates the technique has useful applications in increasing ridge height to permit implant placement inferior to the sinus floor. [ABSTRACT FROM AUTHOR]

Biphasic calcium phosphate (BCP) containing β-tricalcium phosphate and manganese (Mn)-substituted hydroxyapatite (HAP) was synthesized. Biomedical scaffolds were prepared using this synthesized powder on a sacrificial polyurethane sponge template after the incorporation of mangiferin (MAN). Mn was substituted at a concentration of 5% and 10% in HAP to examine the efficacy of Mn at various concentrations. The phase analysis of the as-formed BCP scaffold was carried out by X-ray diffraction analysis, while the qualitative observation of morphology and the osteoblast cell differentiation were carried out by scanning electron microscopy and confocal laser scanning microscopy techniques. Gene expressions of osteocalcin, collagen 1, and RUNX2 were carried out using qRT-PCR analyses. Significantly higher (p < 0.05) levels of ALP activity were observed with extended osteoblast induction on the mangiferin-incorporated BCP scaffolds. After characterization of the specimens, it was found that the scaffolds with 10% Mn-incorporated BCP with mangiferin showed better osteogenicity and simultaneously the same scaffolds exhibited higher anti-bacterial properties as observed from the bacterial viability test. This study was carried out to evaluate the efficacy of Mn and MAN in BCP for osteogenicity and antibacterial action. [ABSTRACT FROM AUTHOR]

Bacterial infections after implant surgical procedures are a complication observed in many surgeries to treat bone injuries or diseases. Bacteria can attach to the surface of the implant producing biofilms, and if treatment with antibiotics does not work, further surgery is necessary to remove the infected implant. Among the biomaterials for bone implants, bioceramics based on calcium phosphates (CaPs) such as β-TCP stand out, due to their chemical similarity with bone and high bioresorbability. β-TCP has the characteristic of easily accommodating in its crystalline structure reasonable amounts of doping elements, such as monovalent and trivalent ions, which makes it an efficient transporter of drugs, molecules, and therapeutic ions The objective of this work was the incorporation of bioactive glass (BG 45S5) via sol-gel and silver nanoparticles (Ag-NPs) in β-TCP scaffolds, aiming to confer antimicrobial activity to the scaffolds, without prejudice to biocompatibility. XRD and FT-IR analysis indicated structural changes after the incorporation of BG 45S5 and Ag-NPs in β-TCP scaffolds, and these compounds induced the partial transformation of the β-TCP phase into α-TCP phase and the formation of sodium-calcium silicates and silver silicates. The FT-IR spectra showed characteristic bands of α-TCP after incorporation, in addition to the predominant bands of β-TCP. Biocompatibility after incorporation of BG 45S5 was improved, with a significant increase in cell viability. After the incorporation of Ag-NPs, cell viability was maintained at an acceptable level, no cytotoxic behavior was observed, and the scaffolds showed antibacterial and antifungal activity. The results indicate that BG 45S5 and the Ag-NPs incorporated showed a synergistic behavior, conferring antimicrobial activity to the scaffolds without compromising biocompatibility, showing great potential for applicability in tissue engineering.

Various efforts have been made to develop antibacterial biomaterials capable of also sustaining bone remodulation to be used as bone substitutes and reduce patient infection rates and related costs. In this work, beta-tricalcium phosphate (β-TCP) was chosen due to its known biocompatibility and use as a bone substitute. Metal dopants were incorporated into the crystal structure of the β-TCP, and disks were produced from this material. Magnesium and strontium, as well as copper and silver, were chosen as dopants to improve the osteogenic and antibacterial properties, respectively. The surface of the β-TCP samples was further modified using a femtosecond laser system. Grid and line patterns were produced on the plates’ surface via laser ablation, creating grooves with depths lower than 20 μm and widths between 20 and 40 μm. Raman and FTIR analysis confirmed that laser ablation did not result in the degradation or phase change of the materials, making it suitable for surface patterning. Laser ablation resulted in increased hydrophilicity of the materials, as the control samples (non-ablated samples) have WCA values ranging from 70° to 93° and become, upon laser ablation, superwicking surfaces. Confocal measurements show an increase in specific surface area of 50% to 200% compared to the control. Overall, the results indicate the potential of laser ablation to improve the surface characteristics of β-TCP, which may lead to an improvement in the antibacterial and osteogenic properties of the produced materials.

A new series of Sr-based phosphates, Sr9−xMnxEu(PO4)7, were synthesized using the high-temperature solid-state method in air. It was found that these compounds have the same structure as strontiowhitlockite, which is a β-Ca3(PO4)2 (or β-TCP) structure. The concentration of Mn2+ ions required to form a pure strontiowhitlockite phase was determined. An unusual partial reduction of Eu3+ to Eu2+ in air was observed and confirmed by photoluminescence (PL) and electron spin resonance (ESR) spectra measurements. The PL spectra recorded under 370 nm excitation showed transitions of both 4f5d–4f Eu2+ and 4f–4f Eu3+. The total integral intensity of the PL spectra, monitored at 395 nm, decreased with increasing Mn2+ concentration due to quenching effect of Eu3+ by the Mn2+ levels. The temperature dependence of Eu2+ photoluminescence in a Sr9−xMnxEu(PO4)7 host was investigated. The conditions for the reduction of Eu3+ to Eu2+ in air were discussed.

β-tricalcium phosphate (β-TCP, β-Ca 3 (PO 4) 2) is one of the most attractive biomaterials for bone regeneration and β-TCP macroporous scaffolds are very promising for both cell proliferation and mechanical support. The Additive Manufacturing (AM) process called Direct Ink Writing (DIW), based on the extrusion of a concentrated ceramic slurry, is particularly adapted to resolve the main drawbacks associated with conventional shaping of ceramic scaffolds. In this work, co-doped β-TCP powders were synthetized and used to print macroporous scaffolds by DIW. Doped β-TCP powders have been proved to exhibit higher thermal stability, densification and mechanical properties compared to undoped β-TCP. Two co-doped compositions were produced via the aqueous precipitation technique combining magnesium, strontium, silver and copper cations: Mg-Sr (2.0–2.0 mol%) and Mg-Sr-Ag-Cu (2.0–2.0–0.1–0.1 mol%). DIW slurries were optimized with undoped and co-doped β-TCP with the use of a dispersant and a carboxymethylcellulose and polyethyleneimine mixture to obtain aqueous slurries filled with 42 vol% of powder. Complete rheological characterizations were realized to assess the suitability of the β-TCP slurries for the DIW process (shear-thinning and thixotropic behaviour). The whole processing chain including printing, osmotic drying (PEG 10000) and sintering (1100 °C, 3 h) was optimized to successfully print co-doped β-TCP macroporous scaffolds. Characterizations after sintering showed a reduction of macropores and microcracks using co-doped β-TCP powders as well as improved compressive strengths and densities compared to undoped β-TCP. A significant enhancement of compressive strength values was obtained compared to literature data. [ABSTRACT FROM AUTHOR]

The primary purpose of the study, presented in this article, was to obtain a composite cement material intended for osteanagenesis. The β-tricalcium phosphate powder (β-TCP, β-Ca3(PO4)2) was obtained by the liquid-phase method. Setting and hardening of the cement system were achieved by adding calcium sulfate hemihydrate (CSH, CaSO4·1/2H2O). An aqueous solution of polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), and a PVA/PVP mixture were used as a polymer component. The methods of capillary viscometry and Fourier-transform infrared spectroscopy (FTIR) revealed the formation of intermolecular hydrogen bonds between polymer components, which determines the good miscibility of polymers. The physicochemical properties of the synthesized materials were characterized by X-ray diffraction (XRD) and FTIR methods, and the added amount of polymers does not significantly influence the processes of phase formation and crystallization of the system. The size of crystallites CSD remained in the range of 32–36 nm, regardless of the ratio of polymer components. The influence of the composition of composites on their solubility was investigated. In view of the lower solubility of pure β-TCP, as compared to calcium sulfate dihydrate (CSD, CaSO4·2H2O), the solubility of composite materials is determined to a greater degree by the CSD solubility. Complexometric titration showed that the interaction between PVA and PVP impeded the diffusion of calcium ions, and at a ratio of PVA to PVP of 1/1, the smallest exit of calcium ions from the system is observed. The cytotoxicity analysis results allowed us to establish the fact that the viability of human macrophages in the presence of the samples varied from 80% to 125% as compared to the control. [ABSTRACT FROM AUTHOR]

Guided bone regeneration (GBR) membranes favor periodontal regrowth, but they still have certain limitations, such as improper biodegradation and poor mechanical property. To overcome these shortcomings, we have generated a unique multifunctional membrane. A polycaprolactone/gelatin/β-TCP and alginate/gelatin trilayered construction was fabricated through electrospinning and casting technology. The prepared membranes have suitable physicomechanical and in-vitro properties to confirm the compatibility of the product in the body. Phase analysis, functional groups, surface microstructure, and contact angle were measured as basic characteristics. For a mechanical performance evaluation, the tensile strength at suturing point was measured through pullout tensile strength test, and it showed the suture capability of bi-layered membranes. Highest tensile strength for A75G25 was recorded with 2.9 ± 0.15 MPa with 105% strain. Further, the osteoblast and fibroblast-type cell toxicity results showed that the electrospun membrane offered compatible environment to cells while the alginate sheet was found to be sufficiently capable to suppress the cellular attachment while also being a nontoxic material. Post-implantation, according to the in-vivo conclusions of the tri-layered membrane, there was appreciable bone formation. Compared to an implant without membrane covering, enhanced new bone formation can be identified after 8 weeks of implantation with P1G4β10 membranes-covered site. [ABSTRACT FROM AUTHOR]

A new drug delivery system consisting of clindamycin phosphate entrapped in acid-etched halloysite nanotubes was successfully prepared and characterized. It was then used as an antibacterial component of the multicomponent hydrogel designed as a material for bone regeneration. First, halloysite (HNT) was etched and clindamycin phosphate (CP) was entrapped in both raw and modified nanotubes, resulting in HNT-CP and EHNT-CP systems. They were characterized using SEM, TEM, TGA and FTIR; the entrapment efficiency and release of CP from both systems were also studied. EHNT-CP was then used as an antibacterial component of the two hydrogels composed of alginate, collagen and β-TCP. The hydrogels were prepared using different crosslinking procedures but had the same composition. The morphology, porosity, degradation rate, CP release profile, cytocompatibility, antibacterial activity and ability to induce biomineralization were studied for both materials. The hydrogel obtained by a chemical crosslinking with EDC followed by the physical crosslinking with calcium ions had better properties and was shown to have potential as a bone repair material. [ABSTRACT FROM AUTHOR]

Every year millions of people around the world suffer from joint and bone diseases and require orthopaedic surgery. Owing to its unique properties such as biocompatibility and ability to bond bones with orthopaedic implants, poly methyl-methacrylate (PMMA) is among the most widely used polymer composites for bone cements in orthopaedic and trauma surgery. On the other hand, this material is characterized by low mechanical properties, which can lead to accelerated implant loosening in aggressive environments, such as the human body. Over the years, researchers have studied PMMA, especially its failure mechanism. Various additives to PMMA have been proposed to enhance the mechanical properties of this material. This study investigated the effect of mixing PMMA with α-TCP (PMMA/α-TCP bone cement composite) and β-TCP (PMMA/β-TCP bone cement composite) on its mechanical properties. The study was conducted on commercially available PMMA (Haraeus Palamed) mixed with α-TCP and β-TCP in different concentrations. TCP has bacteriostatic properties and, as a bone compatible material, it stimulates bone regeneration and bone ingrowth, which highly increases the survival rate of PMMA bonding. However, the addition of particles to PMMA can affect mechanical properties of bone cements. In this study, the effects of 0, 1, 2, 3, 5, 8 and 10% dry mass concentration of TCP in bone cement on the mechanical properties of PMMA were investigated. Samples were subjected to compressive loading. This loading mode is typical of the human body after joint prosthesis implantation. The analysis involved comparing selected mechanical parameters of samples prepared according to manufacturer's instructions and of samples prepared with the addition of α-TCP and β-TCP. Results demonstrated that the addition of β-TCP, whose crystals are triangular, did not affect the mechanical properties of PMMA. On the other hand, the addition of more than 3% dry mass α-TCP, the inner structure of which is hexagonal, led to a slight yet significant decrease in the compressive strength of PMMA. [ABSTRACT FROM AUTHOR]

Traditional non-resorbable bone wax has been used in clinical surgery for more than 100 years. However, residual bone wax has been proven to cause numerous complications. In this study, a novel resorbable bone wax was designed to overcome the disadvantages of traditional non-resorbable bone wax. Alkylene oxide copolymers were used as the main component of resorbable bone wax; additionally, β-tricalcium phosphate and starch microspheres were added to enhance bone regeneration and hemostatic ability. This novel resorbable bone wax has a high potential for clinical translation and is expected to be developed as a substitute for traditional bone wax.

Abstract Background The aim of this multicenter, randomized, open-label, comparative, investigator-blinded study was to investigate the efficacy and safety of recombinant human bone morphogenetic protein 2 (rhBMP-2) combined with β-TCP (rhBMP-2/β-TCP) in alveolar ridge preservation. Materials and methods Eighty-four subjects from three centers were enrolled in this clinical trial. After tooth extraction, rhBMP-2/β-TCP (n = 41, test group) or β-TCP (n = 43, control group) were grafted to the extraction socket with an absorbable barrier membrane for alveolar ridge preservation. Using computed tomography images obtained immediately after and 12 weeks after surgery, changes in the alveolar bone height and width were analyzed for each group and compared between the two groups. Results Both the test and control groups showed a significant decrease in alveolar bone height in the 12 weeks after surgery (both groups, p < 0.0001). However, the test group exhibited a significantly lower decrease in alveolar bone height than the control group (p = 0.0004). Alveolar bone width also showed significantly less resorption in the test group than in the control group for all extraction socket levels (ESL) (p = 0.0152 for 75% ESL; p < 0.0001 for 50% ESL; p < 0.0001 for 25% ESL). There were no statistically significant differences in the incidence of adverse events between the two groups. No severe adverse events occurred in either group. Conclusions The results of this study suggest that rhBMP-2/β-TCP is a safe graft material that provides a high alveolar bone preservation effect in patients receiving dental extraction. Trial registration Clinicaltrials.gov , NCT02714829 , Registered 22 March 2016