Search Results (293)

Sinus augmentation provides a well-established model for investigating the three-dimensional morphometry and macromolecular dynamics of bone regeneration, particularly when using biphasic calcium phosphate (BCP) graft substitutes. This case series included six biopsies from patients who underwent maxillary sinus augmentation using BCP granules composed of 30% hydroxyapatite (HA) and 70% β-tricalcium phosphate (β-TCP). Bone core biopsies were obtained at healing times of 6 months, 9 months, and 12 months. Histological evaluation yielded qualitative and quantitative insights into new bone distribution, while micro-computed tomography (micro-CT) and Raman microspectroscopy (RMS) were employed to assess the three-dimensional architecture and macromolecular composition of the regenerated bone. Micro-CT analysis revealed progressive maturation of the regenerated bone microstructure over time. At 6 months, the apical regenerated area exhibited a significantly higher mineralized volume fraction (58 ± 5%) compared to the basal native bone (44 ± 11%; p = 0.0170), as well as significantly reduced trabecular spacing (Tb.Sp: 187 ± 70 µm vs. 325 ± 96 µm; p = 0.0155) and degree of anisotropy (DA: 0.37 ± 0.05 vs. 0.73 ± 0.03; p < 0.0001). By 12 months, the mineralized volume fraction in the regenerated area (53 ± 5%) was statistically comparable to basal bone (44 ± 3%; p > 0.05), while Tb.Sp (211 ± 20 µm) and DA (0.23 ± 0.09) remained significantly lower (Tb.Sp: 395 ± 41 µm, p = 0.0041; DA: 0.46 ± 0.04, p = 0.0001), indicating continued structural remodelling and organization. Raman microspectroscopy further revealed dynamic macromolecular changes during healing. Characteristic β-TCP peaks (e.g., 1315, 1380, 1483 cm⁻¹) progressively diminished over time and were completely absent in the regenerated tissue at 12 months, contrasting with their partial presence at 6 months. Simultaneously, increased intensity of collagen-specific bands (e.g., Amide I at 1661 cm⁻¹, Amide III at 1250 cm⁻¹) and carbonate peaks (1065 cm⁻¹) reflected active matrix formation and mineralization. Overall, this case series provides qualitative and quantitative evidence that bone regeneration and integration of BCP granules in sinus augmentation continues beyond 6 months, with ongoing maturation observed up to 12 months post-grafting. Full article

This study aimed to compare the performance of three hydroxyapatite–β-tricalcium phosphate (HA–β-TCP) collagen composite grafts in a canine model for extraction socket preservation. Eight mongrel dogs underwent atraumatic bilateral mandibular premolar extraction, and sockets were randomly grafted with HBC28 (20% high-crystalline HA, 80% β-TCP bovine collagen), HBC37 (30% HA, 70% β-TCP, bovine collagen), or HPC64 (60% HA, 40% β-TCP, porcine collagen). Grafts differed in their HA–β-TCP ratio and collagen origin and content. Animals were sacrificed at 4 and 12 weeks, and the healing sites were evaluated using micro-computed tomography (micro-CT) and histological analysis. At 12 weeks, all groups showed good socket maintenance with comparable new bone formation. However, histological analysis revealed that HBC28 had significantly higher residual graft volume, while HPC64 demonstrated more extensive graft resorption. Histomorphometric analysis confirmed these findings, with statistically significant differences in residual graft area and bone volume fraction. No inflammatory response or adverse tissue reactions were observed in any group. These results suggest that all three HA–β-TCP collagen composites are biocompatible and suitable for socket preservation, with varying resorption kinetics influenced by graft composition. Selection of graft material may thus be guided by the desired rate of replacement by new bone. Full article

Cobalt is an essential trace element involved in key biological processes. It serves most notably as a component of vitamin B₁₂ (cobalamin) and a regulator of erythropoiesis. While cobalt deficiency can lead to disorders such as megaloblastic anemia, excess cobalt poses toxicological risks to the thyroid, cardiovascular, and hematopoietic systems. In recent years, cobalt ions (Co²⁺) have gained attention for their ability to mimic hypoxia and promote angiogenesis. This represents a crucial mechanism for tissue regeneration. Cobalt mediates this effect mainly by stabilizing hypoxia-inducible factor 1α (HIF-1α) under normoxic conditions, thereby upregulating angiogenic genes, including VEGF, FGF, and EPO. Experimental studies—from cell culture to animal models—have demonstrated cobalt-induced enhancement of endothelial proliferation, migration, and microvascular formation. Emerging evidence also indicates that Co²⁺-stimulated macrophages secrete integrin-β1-rich exosomes. These exosomes enhance endothelial motility and tubulogenesis independently of VEGF. Furthermore, cobalt-modified biomaterials have been developed to deliver cobalt ions in a controlled manner. Examples include cobalt-doped β-tricalcium phosphate or bioactive glasses. These materials support both angiogenesis and osteogenesis.This review summarizes current findings on cobalt’s role in angiogenesis. The emphasis is on its potential in cobalt-based biomaterials for tissue engineering and regenerative medicine. Full article

Although publications have documented the osteo-inductive effects of various bioactive materials on tissue sections, the associated morphologic patterns of tissue remodeling pathways at the cellular level have not been detailed. Therefore, we present a comparative histopathological follow-up evaluation of bone defect repair mediated by silica aerogels and methacrylate hydrogels over a 6-month period, which is the widely accepted time course for complete resolution. Time-dependent microscopic analysis was conducted using the “critical size model”. In untreated rat calvaria bone defects (control), re-ossification exclusively started at the lateral regions from the edges of the remaining bone. At the 6th month, only a few new bones were formed, which were independent of the lateral ossification. The overall ossification resulted in a 57% osseous encroachment of the defect. In contrast, aerogels (AE), hydrogels (H), and their β-tricalcium-phosphate (βTCP)-containing counterparts, which were used to fill the bone defects, characteristically induced rapid early ossification starting from the 1st month. This was accompanied by fibrous granulomatous inflammation with multinucleated giant macrophages, which persisted in decreasing intensity throughout the observational time. In addition to lateral ossification, multiple and intense intralesional osseous foci developed as early as the 1st month, and grew progressively thereafter, reflecting the osteo-inductive effects of all compounds. However, both βTCP-containing bone substituents generated larger amounts and more mature new bones inside the defects. Nevertheless, only 72.8–76.9% of the bone defects treated with AE and H and 80.5–82.9% of those treated with βTCP-containing counterparts were re-ossified by the 6th month. Remarkably, by this time, some intra-osseous hydrogels were found, and traces of silica from AE were still detectable, indicating these as the causative agents for the persistent osseous–fibrous granulomatous inflammation. When silica or methacrylate-based bone substituents are used, chronic ossifying fibrous granulomatous inflammation develops. Although 100% re-ossification takes more than 6 months, by this time, the degree of osteo-fibrous solidification provides functionally well-suited bone repair. Full article

Background: Due to limitations of fluoride (F) treatment as a main caries preventive measure, it is important to consider the use of other dental caries preventive measures to reduce caries prevalence, especially in its early stages. Recently, new remineralizing agents appeared on the market, with their commercial availability in a variety of oral care products. Objectives: The purposes include providing a scoping review that represents caries remineralizing efficacies of only commercially available products and their existing adverse effects (if it is presented) and ensuring that only evidence-based approved products are included. Methods: The following databases were used in searching scientific literature on 28 October 2024: PubMed, PubMed Advanced Search, MeSH database, and PubMed Clinical Queries. The study selection criteria were as follows: for laboratory, in vitro, and/or in situ—remineralization of enamel-scanning electron microscopy, spectroscopy, microhardness test, light microscopy, profilometry, transverse microhardness microradiography, integrated mineral loss, light microscopy, photothermal radiometry; if it was a randomized controlled trial—CONSORT protocol, ICDAS system (to detect dental caries), diagnostic additional devices; antibacterial ability-colony forming units, DNA-based sequencing, scanning electron microscopy, crystal violet staining, and confocal laser scanning microscopy. Results: This review includes 98 papers: 14 of them describing the current status of caries patterns in the world, 60 studies (45 laboratory studies and 15 RCTs), and 24 systematic reviews were analyzed in order to detect whether new remineralizing agents can replace fluoride in further caries prevention. Conclusions: All reviewed new remineralization agents could be used without additives to treat early caries lesions, but the combination with F promotes better remineralization. Only HAP demonstrated its potential to serve as an alternative to fluoride in oral care products. However, further clinical studies are needed to prove its role in the remineralizing process of initial caries lesions. One also needs to ensure that both the clinical trials and in vitro lab studies use the best gold standards to validate any changes in the tooth structure, both remineralization and demineralization. Full article

Aim: to evaluate the bone regeneration capacity of two alloplastic biomaterials in a critical-size rat calvarial defect model. Methods: A total of 80 rats were randomized into 8 groups of 10 animals each. An Ø8 mm, critical-size calvarial defect was created, and the following treatments were randomly allocated: sham surgery, deproteinized bovine bone mineral (DBBM) + collagen membrane (CM), poly-(lactic-co-glycolic-acid) (PLGA)-coated pure phase β-tricalcium phosphate (β-TCP), or PLGA-coated 60% hydroxyapatite (HA):40%β-TCP. Animals were allowed to heal for 2 and 6 weeks. Microcomputed tomography (μCT) was used to evaluate mineralized tissue and biomaterial displacement. Histological samples were used to evaluate new bone formation. Results: μCT analysis showed no significant differences among groups for total volume of mineralized tissue or residual biomaterials. DBBM + CM showed significantly increased horizontal biomaterial displacement at 2 weeks but not at 6 weeks. Histological analysis showed that sham surgery had a significantly higher percentage of bone area fraction than the DBBM + CM and PLGA + β-TCP at 2 weeks, but not at 6 weeks. Residual biomaterial area fraction showed no significant differences among experimental groups at any healing time. Conclusions: The alloplastic biomaterials showed suitable construct integrity and retention in the defect. All biomaterials were associated with limited new bone formation comparable to the sham surgery control. Full article

Bone graft substitutes combining the mechanical features of poly-ε-caprolactone (PCL) and the bioactivity of β-tricalcium phosphate (β-TCP) have been widely reported in the literature. Surprisingly, however, very little is known about the incorporation of carbonate at a biomimicking level. The authors studied β-TCP/PCL composites at 20 wt.% and 40 wt.%, either enriched or not with sodium bicarbonate (at 2 wt.% and 4 wt.%), through SEM and EDX analyses; surface free energy estimation; pH measurement after 1, 2, and 3 days of incubation in cell media; nanoindentation; and a protein adsorption test with bovine serum albumin. The early biological response was assessed using adipose mesenchymal stem cells, as an established in vitro model, via cellular adhesion (20 min), spreading (24 h), and viability assays (1, 3, 7 days). By increasing the β-TCP content, the composites’ hardnesses and Young’s moduli (EiT) were improved, as well as their protein adsorption compared to neat PCL. Sodium bicarbonate increased the polar component of the surface energy, alkalinized the composite with a higher β-TCP content, and attenuated its early negative cell response. Further investigation is needed to deepen the knowledge of the mechanisms underpinning the mechanical features and long-term biological behavior. Full article

Objectives: This study aimed to compare in vitro the protective effect of two enamel remineralizing agents, a varnish containing β-tricalcium phosphate with sodium fluoride (β-TCP-F) and a paste containing casein phosphopeptide-amorphous calcium phosphate with sodium fluoride (CPP-ACP-F), on artificially demineralized human enamel. Methods: A total of 120 human third molar enamel specimens were randomly assigned to four groups (n = 30 each): Group I (healthy enamel, control), Group II (initially demineralized, lesioned enamel), Group III (demineralized enamel and treated with β-TCP-F), and Group IV (demineralized enamel and treated with CPP-ACP-F). Groups II–IV underwent, for 15 days, a daily pH cycling regimen consisting of 21 h of demineralization under pH 4.4, followed by 3 h of remineralization under pH 7. Groups III and IV were treated with either β-TCP-F or CPP-ACP-F, prior to each 24 h demineralization–remineralization cycle. Fluoride ion release was measured after each pH cycle. Surface hardness, roughness, wettability, and Streptococcus mutans biofilm formation were assessed on days 5, 10, and 15 after a daily pH cycle. Results: CPP-ACP-F treatment showed a larger improvement in surface hardness (515.2 ± 10.7) compared to β-TCP-F (473.6 ± 12.8). Surface roughness decreased for both treatments compared to initially lesioned enamel; however, the decrease in roughness in the β-TCP-F group only reached a value of 1.193 μm after 15 days of treatment, a significantly larger value in comparison to healthy enamel. On the other hand, the decrease in roughness in the CPP-ACP-F treatment group reached a value of 0.76 μm, similar to that of healthy enamel. Contact angle measurements indicated that wettability increased in both treatment groups (β-TCP-F: 71.01°, CPP-ACP-F: 65.24°) compared to initially lesioned samples in Group II, reaching WCA values similar to or smaller than those of healthy enamel surfaces. Conclusions: Both treatments, β-TCP-F and CPP-ACP-F, demonstrated protective effects against enamel demineralization, with CPP-ACP-F showing superior enhancement of surface hardness and smoother enamel texture under in vitro pH cycling conditions. β-TCP-F varnish and CPP-ACP-F paste treatments counteracted surface modifications produced on human healthy enamel by in vitro demineralization. Full article

Effective osteogenesis for bone regeneration is still considerably challenging for a porous β-tricalcium phosphate (β-TCP) scaffold to achieve. To overcome this challenge, hollow manganese dioxide (H-MnO₂) nanoparticles with an urchin-like shell structure were prepared and added in the porous β-TCP scaffold. A template-casting method was used to prepare the porous H-MnO₂/β-TCP scaffolds. As a control, solid manganese dioxide (S-MnO₂) nanoparticles were also added into β-TCP scaffolds. Human bone mesenchymal stem cells (hBMSC) were seeded in the porous scaffolds and characterized through cell viability assay and alkaline phosphatase (ALP) assay. Results from in vitro protein loading and releasing experiments showed that H-MnO₂ can load significantly higher proteins and release more proteins compared to S-MnO₂ nanoparticles. When they were doped into β-TCP, MnO₂ nanoparticles did not significantly change the surface wettability and mechanical properties of porous β-TCP scaffolds. In vitro cell viability results showed that MnO₂ nanoparticles promoted cell proliferation in a low dose, but inhibited cell growth when the added concentration went beyond 0.5%. At a range of lower than 0.5%, H-MnO₂ doped β-TCP scaffolds promoted the early osteogenesis of hBMSCs. These results suggested that H-MnO₂ in the porous β-TCP scaffold has promising potential to stimulate osteogenesis. More studies would be performed to demonstrate the other functions of urchin-like H-MnO₂ nanoparticles in the porous β-TCP. Full article

Implant-associated infections, particularly those linked to Staphylococcus aureus (S. aureus), continue to compromise the clinical success of β-tricalcium phosphate (β-TCP) implants despite their excellent biocompatibility and osteoconductivity. This investigation aims to tackle these challenges by integrating femtosecond (fs)-laser surface processing with two complementary strategies: ion doping and functionalization with green-synthesized silver nanoparticles (AgNPs). AgNPs were produced via fs-laser photoreduction using green tea leaf extract (GTLE), noted for its anti-inflammatory and antioxidant properties. Fs-laser processing was applied to modify β-TCP scaffolds by systematically varying scanning velocities, fluences, and patterns. Lower scanning velocities generated organized nanostructures with enhanced roughness and wettability, as confirmed by scanning electron microscopy (SEM), optical profilometry, and contact angle measurements, whereas higher laser energies induced significant phase transitions between hydroxyapatite (HA) and α-tricalcium phosphate (α-TCP), as revealed by X-ray diffraction (XRD). AgNP-functionalized scaffolds demonstrated markedly superior antibacterial activity against S. aureus compared to the ion-doped variants, attributed to the synergistic interplay of nanostructure-mediated surface disruption and AgNP-induced bactericidal mechanisms. Although ion-doped scaffolds exhibited limited direct antibacterial effects, they showed concentration-dependent activity in indirect assays, likely due to controlled ion release. Both strategies promoted osteogenic differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) under defined conditions, albeit with transient cytotoxicity at higher fluences and excessive ion doping. Overall, this approach holds promise for markedly improving antibacterial efficacy and osteogenic compatibility, potentially transforming bone regeneration therapies. Full article

Background/Objectives: Mandibular reconstruction following trauma or oncologic resection is crucial for restoring function and aesthetics. While autologous bone grafting remains the gold standard, it presents challenges such as donor site morbidity and graft availability. Bone tissue engineering (BTE) offers an innovative alternative, integrating scaffolds, osteogenic cells, and bioactive factors to regenerate functional bone. This systematic review evaluates BTE strategies for mandibular reconstruction, focusing on critical-sized defects in large animal models and their translational potential for clinical applications. Methods: A systematic review was performed following PRISMA guidelines. Eligible studies involved large animal models and critical-sized mandibular defects treated with at least two BTE components (scaffold, osteogenic cells, or growth factors). Quality and bias assessments were conducted using ARRIVE guidelines and SYRCLE tools. Results: Of the 6088 studies screened, 27 met the inclusion criteria, focusing on critical-sized mandibular defects in large animal models such as pigs, sheep, and dogs. Common scaffolds included β-tricalcium phosphate (β-TCP), poly-lactic-co-glycolic acid (PLGA), and polycaprolactone (PCL), frequently combined with bone marrow-derived mesenchymal stem cells (BMSCs) and growth factors like recombinant human bone morphogenetic protein-2 (rhBMP-2). Preclinical outcomes demonstrated effective bone regeneration, vascularization, and biomechanical restoration. Advanced strategies, including in vivo bioreactors and 3D-printed scaffolds, further enhanced regeneration. However, challenges such as incomplete scaffold degradation, hypoxic conditions within constructs, and variability in growth factor efficacy and dose optimization were observed, emphasizing the need for further refinement to ensure consistent outcomes. Conclusions: BTE shows promise in mandibular reconstruction, achieving bone regeneration and functional restoration in preclinical models of critical-sized defects. However, challenges such as scaffold optimization, vascularization enhancement, and protocol standardization require further investigation to facilitate clinical translation. These findings emphasize the need for refinement to achieve consistent, scalable outcomes for clinical use. Full article

The expansion of fisheries and aquaculture in recent decades has led to a substantial increase in fish by-products. This study investigates the extraction and characterization of calcium phosphates from the by-products of representative species in these industries, aiming to identify potential sources for biotechnological and pharmaceutical applications. Clean bones obtained by enzyme hydrolysis from the heads, central skeletons, and/or tails of Atlantic horse mackerel, blue whiting, hake, mackerel, and farmed turbot were subjected to calcination to obtain calcium phosphates. The clean bone content in terms of nitrogen, lipids, organic matter, total protein, and amino acids was evaluated together with the chemical bonds, structures, and elemental composition of calcium phosphates. Results indicated a significantly higher yield of wet bone recovery (23%, p < 0.05) for the central skeleton of Atlantic horse mackerel and the highest mineral fraction for the heads of Atlantic horse mackerel (73.2%), followed by that of blue whiting (72.6%). Hake and turbot presented the lowest mineral fractions and, therefore, the highest protein content (27–31%, p < 0.05), with significant levels of collagen-related amino acids (p < 0.05). X-ray diffraction (XRD) and Fourier-transform Raman spectroscopy (FT-Raman) confirmed the biphasic calcium phosphate composition for most samples based on hydroxyapatite with contributions of whitlockite/β-tricalcium phosphate. The highest contribution to the non-apatite phase was made by the central skeletons of both mackerel and Atlantic horse mackerel. Full article

Background: Sinus-lift (SL) is a pre-prosthetic procedure with the objective of increasing bone height to achieve implant insertion primary stability in implant-supported prostheses. The biomechanical properties of SL augmentation materials are influenced by their origin, manufacture, bioactive substances addition, receiver, and surgical procedure. This systematic review provides insights into state-of-the-art SL biomaterials, focusing on autologous bone grafting as the gold standard. Methods: The study followed the PRISMA flow diagram, searching WoS (Web of Science), Embase, Cochrane, and PubMed databases using the search terms «sinus lift» OR «sinus augmentation» OR «bone graft» OR «bovine» OR «porcine» OR «autologous» OR «allogenic» OR «xenogeneic» OR «alloplastic» OR «hydroxyapatite» OR «β-tricalcium phosphate (β-TCP)» OR «equine» OR «PRF». Results: The highest bone gain was provided by Bioglass at 42%. Articles written between 2014 and 2024 in English or French, containing human studies and with full text available, were included. Participants were required to be in good general health, without acute, chronic, or congenital diseases, or substance abuse (drugs, alcohol, or nicotine). SL surgery was performed using the lateral approach, with no Schneiderian membrane perforation or postoperative complications. The network meta-analysis was conducted using the R statistical computing environment. To assess the inconsistency between direct and indirect evidence, we used a net heat plot. To evaluate heterogeneity across studies, we used the chi-squared-based Q-test and I² statistic. A significance level of 0.05 was applied throughout all analyses. Results: Allogeneic bovine bone and hydrox yapatite demonstrated the lowest resorption rates. Significant differences were found for residual graft and connective tissue between allogenous bovine bone (ABB) + AlB vs. β-TCP + PRF (p = 0.028); ABB + AlB vs. β-TCP (p = 0.034); ABB + AlB vs. BCP (p = 0.037). Meta-analysis showed that the overall heterogeneity was 51.8% (6.9–75%; p = 0.019), with significant heterogeneity within designs (p = 0.007) and no significant heterogeneity between designs (p = 0.39). AB had a better bone regeneration ratio compared to many of the other interventions, but only two passed the threshold of significance: A1B and B-TCP + AB. Conclusions: A grafting material’s superiority is determined by its new bone formation ratio, connective tissue integration, residual graft content, and bone resorptionratio. Although autologous bone grafting has exhibited superior bone regeneration compared to other biomaterials, it was not favored due to its unpredictable connective tissue concentration and bone resorption ratio. Additionally, autologous bone exhibited the fastest metabolic turnover among all grafting materials. Full article

Current research in bone tissue engineering is focused not only on basic parameters of the materials, such as biocompatibility and degradation rate but also on intrinsic osteogenic and antimicrobial properties, essential to provide a rapid tissue regeneration without negative effects due to periprosthetic infections, that may result in revision surgeries. One of the major strategies to enhance the osteogenic and antimicrobial performance of calcium phosphates is the ionic substitution, in particular, with magnesium and borates. In this study, we focused on the synthesis of boron-substituted tricalcium phosphate (B-TCP) with a target of 5 mol.% substitution via the solid-state synthesis with mechano-activation. Synthesis from raw precursors, without the preliminary brushite wet precipitation, led to the primary phase of β-TCP, which was proved by the XRD analysis. According to the IR-spectroscopy and ³¹P NMR analysis, boron substitution occurred in the synthesized sample. The developed material showed a modest antibacterial performance against E. coli, with 13.5 ± 5.0% growth inhibition, and E. faecalis, with 16.7 ± 5.5% inhibition. The biocompatibility of β-TCP and B-TCP was tested through the MTT assay and osteogenic differentiation of the mesenchymal stromal cells. The proposed synthesis approach can be useful for the fabrication of B-TCP ceramics for bone tissue engineering. Full article

Octacalcium phosphate (OCP) has been shown to exhibit an osteogenic property and, therefore, has been utilized recently as a bone substitute, clinically. However, the stimulatory capacity for induced pluripotent stem (iPS) cells is not known. This study investigated whether OCP enhances osteoblastic differentiation of three-dimensionally cultured spheroids of iPS cells compared to hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP). Mouse iPS cells were mixed with smaller (less than 53 μm) or larger (300–500 μm) sizes of calcium phosphate (CaP) granules and cultured in a laboratory-developed oxygen-permeable culture chip under minimizing hypoxia for up to 21 days. Osteoblastic differentiation was estimated by the cellular alkaline phosphatase (ALP) activities. The degree of supersaturation (DS) with respect to CaP phases was determined from the media chemical compositions. Incubated CaP materials were characterized by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The culture promoted well the formation of hybrid spheroids of CaP materials and iPS cells regardless of the type of materials and their granule sizes. The ALP activity of OCP was about 1.5 times higher than that of β-TCP and HA in smaller granule sizes. FTIR, XRD, and DS analyses showed that larger OCP granules tended to hydrolyze to HA slightly faster than smaller granules with time while HA and β-TCP materials tended to remain unchanged. In conclusion, the results suggest that OCP enhances the osteogenic differentiation of iPS cells more than HA and β-TCP through a mechanism of hydrolyzing to HA. This inherent material property of OCP is essential for enhancing the osteoblastic differentiation of iPS cells. Full article