Search Results (336)

Hydroxyapatite (HAp) is a key bioceramic for biomedical applications, but conventional pressureless sintering (PS) requires high temperatures that can promote phase degradation. Here, we compare PS (1100 °C/180 min) and cold sintering process (CSP) (150 °C/450 MPa/30 min) for pure HAp and an HAp composite containing 4 wt.% niobium–phosphate bioglass (BG), using a 2 M H₃PO₄ transient liquid (10 wt.%). CSP increased relative density from 73.10% to 79.92% for HAp and from 68.43% to 83.54% for HAp/BG, representing up to a 22.1% gain compared with PS. One-way ANOVA confirmed a significant effect of processing route/composition on relative density (F(3,24) = 919.69, p < 0.05), and Tukey HSD indicated that all groups differed statistically. SEM revealed a markedly more consolidated and homogeneous microstructure for CSP, particularly for HAp/BG, consistent with enhanced dissolution–reprecipitation and pore filling. XRD showed that PS at 1100 °C led to partial HAp degradation with β-TCP formation, whereas CSP preserved the HAp phase with broader peaks, smaller crystallite size, and higher specific surface area. These results demonstrate CSP as an efficient low-temperature alternative for densifying HAp-based bioceramics, with BG addition further improving consolidation. Full article

There has been much development of composites of calcium phosphate and polymers for use as artificial bone, with other applications still ongoing, and clarification of the in vivo absorption mechanism is considered an important perspective. In order to clarify the absorption mechanism of bioabsorbable materials used for artificial bones and bone grafts, we prepared composites of calcium phosphate and polymers and conducted in vivo experiments in experimental animals using composites as implantation samples. Two typical types of calcium phosphate, β-tricalcium phosphate (β-TCP) and unsintered hydroxyapatite (uHA), were used as calcium phosphate, and copolymers of poly-dl-lactide-co-glycolide (PDLGA) and poly-l-lactide-co-glycolide (PLGA) were used as polymers. For samples composed of PDLGA and calcium phosphates, the weight ratios of calcium phosphate were set at 40% and 10% for uHA and 40% for β-TCP (uHA(40), uHA(10) and β-TCP(40), respectively). A composite sample of PLGA and uHA was also prepared with a weight ratio of 10% uHA (uHA(10)/PLGA), intending slow degradation of the polymer matrix compared to PDLGA. The samples were implanted in the metaphysis and diaphysis region of rabbits’ femur for up to 48 weeks. In this study, positron emission tomography/X-ray computed tomography (PET/CT) was used to continuously evaluate the changes in the samples and the accumulation of cells in the animals, and histological evaluation was performed, focusing on the time of characteristic changes in the PET/CT to confirm the cell types. The results are summarized as follows: (1) the absorption mechanism of the materials used in this study was suggested to be mainly phagocytosis by macrophages; (2) the disappearance rate was faster for β-TCP(40) compared with uHA(40); and (3) uHA(10), having a lower proportion of uHA, is not prone to aggregation and exhibited a similar disappearance result to β-TCP(40). These results suggest that phagocytosis by macrophages is the dominant path in resorption of the bioresorbable materials, and the resorption period varies depending on the type of polymer. It is important to optimize the type and amount of polymers and calcium phosphate in order to achieve a degradation rate of bioresorbable materials that corresponds to the extent of damage in the healing area. Full article

This study aimed to quantify horizontal and vertical bone gain using superimposition of preoperative and postoperative cone beam computed tomography (CBCT) in severe alveolar ridge defects treated with a modified guided bone regeneration (GBR) technique based on customized titanium occlusive barriers with a window design, combined with autologous blood clot and β-tricalcium phosphate (β-TCP). In this prospective case series, 13 patients (28 defects) were treated. Customized titanium barriers were digitally designed based on CBCT data and manufactured by laser sintering. The barriers were fixed over the defects and filled with a mixture of an autologous blood clot and β-TCP, providing an osteoconductive scaffold within a stable regenerative compartment. A standardized window-based follow-up protocol was applied during healing, including irrigation and controlled deepithelialization. Primary outcomes were horizontal and vertical bone gain, assessed by pre- and postoperative CBCT superimposition. Histological evaluation was performed at the time of implant placement. After 8 months, significant bone gain was observed, with a mean horizontal gain of 4.50 ± 2.02 mm and a mean vertical gain of 4.40 ± 2.82 mm (p < 0.0001), confirmed by linear mixed-effects models and patient-level sensitivity analyses (p < 0.001). Histological analysis revealed well-vascularized newly formed bone with active osteoblasts and no inflammatory response. Keratinized gingiva formation was observed at all sites. One minor complication (mild screw loosening) was recorded and successfully resolved. This study is presented as a prospective case series; therefore, the results should be interpreted as exploratory evidence and do not allow direct comparisons or conclusions regarding equivalence or superiority over other GBR techniques. The present report specifically evaluates the regenerative phase prior to functional loading; therefore, although implants were placed according to protocol, implant survival and long-term functional outcomes were not assessed and cannot be inferred from these data. Within the limitations of this prospective case series, customized titanium occlusive barriers with a window design demonstrated promising results for horizontal and vertical bone augmentation and keratinized gingiva formation, without the need for autologous bone grafts or primary wound closure. Full article

Background: Hyaluronic acid (HA) and β-tricalcium phosphate (β-TCP) are widely used biomaterials in periodontal and alveolar regeneration; however, their complementary biological roles across soft- and hard-tissue healing have not been jointly assessed in a single review. Objective: to systematically evaluate clinical and translational evidence regarding the adjunctive use of HA in periodontal therapy and the regenerative performance of β-TCP in alveolar bone reconstruction. Methods: A systematic search was conducted across PubMed/MEDLINE, Scopus, Web of Science Core Collection, and Embase for studies published between 1 January 2015 and 1 October 2025. Randomized and non-randomized clinical studies evaluating HA as an adjunct to periodontal therapy and β-TCP in ridge preservation or augmentation were included. In vitro studies were considered when providing mechanistic insight relevant to clinical outcomes. Screening, data extraction, and qualitative synthesis were performed according to PRISMA 2020 guidelines. Results: Database searching identified 312 records. After removal of duplicates, 241 records were screened, of which 179 were excluded. Sixty-two full-text articles were assessed for eligibility, and twenty studies met the inclusion criteria (twelve clinical; eight in vitro). Across non-surgical periodontal therapy trials, adjunctive HA demonstrated modest but consistent additional improvements in probing depth reduction (~0.8–1.5 mm) and clinical attachment gain (~0.5–1.2 mm) compared with mechanical therapy alone, particularly in deeper defects and systemically compromised patients. Clinical studies on β-TCP reported predictable dimensional bone preservation and stable implant feasibility, supported by histologic evidence of scaffold-guided new bone formation. In vitro findings indicated that HA modulates biofilm-induced inflammation and supports fibroblast and epithelial cell function, whereas β-TCP promotes osteoblast activity and controlled osteoclast-mediated remodeling. Conclusions: HA and β-TCP demonstrate complementary regenerative roles, with HA primarily enhancing soft-tissue resolution and inflammatory modulation and β-TCP providing osteoconductive structural support for bone regeneration. Current evidence supports their selective integration in personalized regenerative approaches; however, standardized outcome reporting and longer-term trials are required to establish the clinical value of sequential or combined application. Full article

Background/Objectives: Nonunion bone healing results from a critical size defect that fails to bridge a bone injury to produce bony union. Novel approaches are critical for refining therapy in clinically challenging bone injuries, but the complex and coordinated nature of fracture callus tissue development requires study outside of the simple closed murine fracture model. Methods: We have utilized a three-dimensional printing approach to develop a scaffold construct with layers designed to sequentially release small molecule therapy within the tissues of a murine endochondral segmental defect to augment different mechanisms of fracture repair during critical stages of nonunion bone healing. Initially, a sonic hedgehog (SHH) agonist is released from a fibrin layer to promote chondrogenesis. A prolyl-hydroxylase domain (PHD)2 inhibitor is subsequently released from a β-tricalcium phosphate (β-TCP) layer to promote hypoxia-inducible factor (HIF)-1α regulation of angiogenesis. This sequential approach to therapy delivery is assisted by the inclusion of bone marrow stromal cells (BMSCs) to increase the cell substrate available for the small molecule therapy. Results: Immunohistochemistry of fracture callus tissue revealed increased expression of PTCH1 and HIF1α, targets of hedgehog and hypoxia signaling pathways, respectively, in the SAG21k/IOX2-treated mice compared to vehicle control. MicroCT and histology analyses showed increased bone in the fracture callus of mice that received therapy compared to control vehicle scaffolds. Conclusions: While our findings establish feasibility for the use of BMSCs and small molecules in the fibrin gel/β-TCP scaffolds to promote new bone formation for segmental defect healing, further optimization of these approaches is required to develop a fracture callus capable of completing bony union in a large defect. Full article

Bone graft substitutes are extensively investigated for addressing critical-size bone defects; however, their efficacy is limited by inadequate bone regeneration and subpar handling properties. Herein, we compared the bone regenerative capacity of CaO–SiO₂–P₂O₅–B₂O₃-based bioactive glass (BGS-7) macrobeads with that of β-tricalcium phosphate (β-TCP) beads and evaluated their performance when incorporated into hydrogels to improve their handling properties. BGS-7 macrobeads were fabricated via alginate crosslinking and heat treatment, and their physicochemical properties and microstructures were characterized. In a rabbit calvarial defect model, BGS-7 macrobeads, heat-treated at 600 and 800 °C, exhibited superior bone bridging and degradation than size-matched β-TCP macrobeads. To further evaluate their regenerative potential, critical-size defects (6 mm diameter × 10 mm depth) were created in the rabbit femoral condyle. To enhance clinical applicability, BGS-7 beads were incorporated into cellulose-based hydrogels and implanted into the defects. Radiographic and histomorphometric analyses demonstrated that bone formation and stable fixation achieved with hydrogel formulations containing BGS-7 microbeads and Laponite were more pronounced than those with BGS-7 beads alone. The findings suggest that BGS-7 macrobeads, particularly when combined with microbead- and Laponite-containing hydrogels, represent a promising bone graft substitute with improved regenerative and handling properties compared with using BGS-7 beads alone. Full article

Vascularization is one of the key components of tissue engineering and must accompany the ingrowth of new tissues to establish an environment conducive to repair and regeneration of damaged tissue. The overarching objective of this study was to investigate whether the hyper-crosslinked carbohydrate polymer (HCCP) could promote the establishment of new vasculature compared to hydroxyapatite/beta-tricalcium phosphate (HA/β-TCP), which is widely used in orthopedic procedures. Sprague Dawley rats (n = 12) were implanted subcutaneously with HCCP or HA/β-TCP and evaluated histologically for the ingrowth of new vasculature at 3, 14, and 28 days post-implantation. HCCP showed significantly greater levels of vascularization when compared to HA/β-TCP at all time points evaluated (p < 0.05). HA/β-TCP showed transient inflammation at 14 days post-implantation, whereas minimal immune activities were noted in HCCP. These findings suggest that HCCP promotes the establishment of new vasculature without a significant immune response. Full article

New nano-biomaterials for specific dentistry applications have been developed thanks to contributions from materials science. The present work aims to characterize the physicochemical properties of a composite nanomaterial scaffold in block form for maxillofacial bone regeneration applications. The scaffold was composed of block-shaped elements and consisted of a mixture of nano-hydroxyapatite, β-tricalcium phosphate, and type I collagen of bovine origin. Collagen I molecule is biodegradable, biocompatible, easily available, and a natural bone matrix component. The biomaterial was analyzed using a range of methods, including scanning electron microscopy (SEM), transmission electron microscopy (TEM), chemical composition microanalysis, and X-Ray diffractometry (XRD). The wettability was measured. This was carried out by measuring the contact angle of a 0.9% NaCl solution on the surface. Differential scanning calorimetry (DSC) was used to measure the phase transformation temperatures. In the SEM and TEM analyses, it was possible to identify the layers of the materials and, with microanalysis, quantify their chemical composition. The XRD spectra showed the presence of nano-hydroxyapatite and ß-TCP. Wettability testing revealed that the material is highly hydrophilic, and BM-MSC culture analyses demonstrated that the biomaterial can promotes cell adhesion and interaction. The higher wettability is due to the higher density of the porous material observed in the SEM analysis. The results of the DSC testing showed that the sample analyzed undergoes endothermic transitions and transformation between 25 and 150 °C. The first phase transformation during heating occurs at 61.1 °C, which is above body temperature. The findings demonstrated that the composite was devoid of any contamination arising from manufacturing processes. It can be concluded that the n-HA/β-TCP and type 1 collagen are free of manufacturing contaminants. They also have high wettability, which increases the spreading of body fluids on the biomaterial’s surface and its interactions with cells and proteins. This makes them suitable for clinical application. Full article

This study aimed to develop a sustainable route for processing biogenic calcium carbonate from Perna perna mussel shell waste and converting it into hydroxyapatite (HA), as well as to evaluate its potential for bone and dental tissue engineering applications. Mussel shells were decarbonized (400 °C), milled, and converted to HA via wet chemical precipitation using a nominal Ca/P molar ratio of 1.67 during synthesis followed by thermal treatment (900 °C). Comprehensive characterization included SEM, FTIR, XRD, Raman spectroscopy, XRF, TGA, and BET analysis. Biological evaluation involved cytotoxicity assays (MTT), antimicrobial testing, and odontogenic differentiation studies (Alizarin Red) using SHEDs. Statistical analysis by one-way ANOVA and Tukey post hoc tests (α = 0.05). SEM revealed a microstructured morphology composed of agglomerates, favorable for biomedical applications. FTIR and XRD confirmed the conversion of CaCO₃ to hydroxyapatite, while thermal analysis demonstrated the material’s stability. The HA exhibited secondary minor phase (13%) β-TCP form of calcium phosphate (Ca_2.997H_0.006(PO₄)₂), high crystallinity (about 80%), and nanoscale crystallite size (85 nm, 2.5–5.0 m²/g), despite forming larger agglomerates in suspension. The material showed favorable physicochemical properties (neutral pH, −18.5 mV zeta potential), but no inhibition was detected in antimicrobial testing. In vitro assays showed excellent cytocompatibility (viability > 70% at 12.5 µg/mL) and significant osteogenic potential (high mineralization vs. controls, p < 0.05). Mussel shell-derived HA presents a sustainable, clinically relevant biomaterial with ideal properties for bone regeneration. The study establishes a complete waste-to-biomaterial pipeline while addressing key requirements for dental and orthopedic applications. Full article

This study investigates phase formation in the Sr–Zn–Eu³⁺ orthophosphate system, focusing on double- and triple-phosphates. The isomorphisms and phase formation in Sr_3–1.5xEu_1+x(PO₄)₃, Sr_9–1.5xZn_1.5Eu_x(PO₄)₇, Sr_9.5–1.5xZnEu_x(PO₄)₇, Sr_3–xZn_xEu(PO₄)₃, and Sr_3–xZn_x(PO₄)₂ series were studied using powder X-ray diffraction and Rietveld refinement. A ternary phase diagram was constructed, identifying concentration limits for pure phases and multi-phase regions as well as areas of stabilization of strontiowhitlockite-, palmierite-, eulytite-, and strontiohurlbutite-type phases. The combinatorial complexity of Sr-based phosphates is discussed. The β-Sr₃(PO₄)₂ isostructural to whitlockite was found to exhibit the highest isomorphic capacity for Eu³⁺ cations, which is advantageous for its application as a red-emitting phosphor. Photoluminescence properties were studied, and analyzed based on structural data. Photoluminescence studies confirmed intense red-emission dominated by the ⁵D₀ → ⁷F₂ transition of Eu³⁺, with the β-Sr₃(PO₄)₂-based phosphor showing the highest emission intensity. Full article

Tricalcium phosphate (TCP) bioceramics, available as α- and β-polymorphs, are frequently employed in the production of three-dimensionally (3D) printed bone scaffolds. Although hydrothermal immersion processing (HP) and sintering (S) are commonly adopted as post-printing techniques for bioceramics, a comprehensive comparative analysis of their effects on the osteogenic performance of α- and β-polymorphs in vivo remains inadequately investigated. In this study, α-TCP and β-TCP scaffolds were fabricated via direct ink writing and subjected to hydrothermal immersion processing (α-TCP/HP) and sintering (β-TCP/S) prior to implantation in n = 12 skeletally mature sheep (n = 1 scaffold per group per animal), and the outcome variables were evaluated at 3 and 12 weeks postoperatively (n = 6 sheep per time point). The quantitative results showed no significant differences in bone deposition or scaffold resorption at 3 weeks postoperatively (p = 0.618 and p = 0.898, respectively). However, at 12 weeks, there was a significant increase in osteogenesis and scaffold resorption in the β-TCP/S cohort relative to the α-TCP/HP counterparts (p < 0.001 and p = 0.004, respectively). β-TCP scaffolds subjected to post-print sintering exhibited superior osteoconductive and resorptive profiles compared to hydrothermal immersion-processed α-TCP scaffolds over the 12-week healing period. Full article

Epigallocatechin gallate (EGCG)—the most abundant catechin in green tea—is a promising component of advanced composite biomaterials. The pharmacological activity of EGCG is typically attenuated upon thermal processing, although the exact effects of heating free and modified EGCG in air and vacuum are unknown. To bridge this gap, we herein examined the effects of heating free and modified (in gelatin containing beta-tricalcium phosphate granules) EGCG in vacuum and air (100–220 °C, 1–16 h) on its physicochemical and antioxidant properties using water and ethanol solubility measurements, discoloration and antioxidant activity (2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) assays, ultraviolet–visible spectroscopy, mass spectrometry, nuclear magnetic resonance spectroscopy, and attenuated total reflectance Fourier transform infrared spectroscopy. The antioxidant activity of EGCG-modified gelatin sponges was assessed in vitro using the DPPH assay and in vivo using a calvarial bone defect model in eight-week-old male Sprague–Dawley rats. Free and modified EGCG showed antioxidant activities, which were largely retained after heating in vacuum at 150 °C. These findings show that appropriate heating procedures preserve the antioxidant activity of EGCG and provide insights for the development of EGCG-based biomaterials. Full article

Tooth extraction induces changes in both hard and soft tissues, which may compromise implant placement. Leukocyte- and platelet-rich fibrin (L-PRF) is used to promote tissue healing, either alone or in combination with other grafting materials. Objective: This study aimed to compare post-extraction socket healing using L-PRF alone or combined with a biphasic calcium phosphate graft (HA/β-TCP) after eight weeks. Materials and Methods: 15 patients, both sexes, mean age 56.7 ± 8.2 years, requiring alveolar ridge preservation after single-rooted tooth extraction for subsequent implant placement, were included. Sockets were randomly assigned to four groups: control with blood clot only (CTR), autogenous bone graft (AB), L-PRF membrane (LPRF), and L-PRF combined with HA/β-TCP (LPRFHA). The protocol consisted of tooth extraction and immediate graft placement, followed by bone biopsy at 8 weeks for histomorphometric analysis and implant installation. New Bone Formation (NBF) was quantified from ten photomicrographs per sample using ImageJ software (version 1.54, 5 February 2025). One-way ANOVA with Bonferroni post hoc tests was applied, with statistical significance set at p ≤ 0.05. Results: A significant difference in NBF (%) was observed between the control and LPRFHA groups (p = 0.014), with greater bone formation in the control group (62.4 ± 18.6%) compared with LPRFHA (55.8 ± 17.2%; p = 0.012). No significant differences were found among AB, LPRF, and LPRFHA groups. LPRF and AB showed comparable bone formation (60.2 ± 17.5% and 60.1 ± 20.0%, respectively). Conclusions: L-PRF, either alone or combined with HA/β-TCP, can be used for alveolar ridge preservation in maxillary sockets. L-PRF, alone or with synthetic HA/β-TCP graft, effectively preserves the anterior maxillary ridge for early loading at eight weeks. All treatments achieved bone formation for implant placement, with the blood clot alone showing superior results. Full article

Bone graft materials frequently employed in dental implant placement procedures, including hydroxyapatite and β-tricalcium phosphate (β-TCP), are typically granular in form, which complicates their manipulation and contributes to extended treatment durations. A tissue engineering approach utilizing readily manageable biomaterials in conjunction with mesenchymal stem cells (MSCs) represents the most promising approach in dentistry. This study assessed the bone-augmenting capacity at bone defect sites in inbred rats by seeding dedifferentiated fat (DFAT) cells onto a cotton-like bone graft scaffold composed of β-TCP and poly(L-lactic-co- glycolide) (PLGA), which was subsequently wrapped around titanium. As a control, cotton-like bone graft material without cells was used and wrapped around and transplanted. Four weeks post-implantation, computed tomography (CT) images of the DFAT group revealed a 1.25-fold enhancement in hard tissue formation compared to the control group. Histological analysis revealed compact structure in a dark red color surrounding the cotton-like bone graft material was observed on the titanium surface of DFAT group. Histomorphometric analysis revealed that the amount of hard tissue generated in the DFAT group was approximately 2.5 times higher than that observed in the control group. Moreover, this mineralized tissue demonstrated properties analogous to those observed in cortical bone. Collectively, these findings indicate that the composite of DFAT cells and cotton-like bone graft material holds potential for bone augmentation applications and represents a promising approach for regenerative therapies within the orofacial region. Full article

Calcium phosphates are one of the main materials used in biomedicine for bone regeneration purposes. To improve the properties of biocompatible β-Ca₃(PO₄)₂, doping by bioactive, antibacterial is actively used, as well as luminescent ions. Co-doped phosphates Ca_8−xSr_xZnEu(PO₄)₇ with a β-Ca₃(PO₄)₂ (β-TCP)-type structure were synthesized through solid-state synthesis. The β-TCP-type structure was confirmed using X-ray powder diffraction and FTIR spectroscopy. Photoluminescence data, including excitation and emission spectra, decay curves, lifetime values and quantum yields, were collected for all samples. Ca_8−xSr_xZnEu(PO₄)₇ phosphates exhibit strong red-emission due to 4f-4f transitions of Eu³⁺ ions in disordered oxygen surrounding, with quantum yields reaching 54%. The phosphates demonstrated biocompatibility through MTT assay, with successful differentiation of aMSCs into the osteogenic lineage. Antibacterial activity was tested against four bacteria (E. coli, S. aureus, P. aeruginosa, and E. faecalis) and a fungus (C. albicans). It was found that the samples demonstrated antibacterial properties. The growth of E. coli and E. faecalis is significant inhibited by Ca_8−xSr_xZnEu(PO₄)₇ samples with 0 ≤ x ≤ 6.0. Analysis of mixed salt solubility using Eu³⁺ ions as a fluorescent probe showed that increasing Sr²⁺ concentration in Ca_8−xSr_xZnEu(PO₄)₇ delays both β-TCP phase resorption and HAP phase precipitation. These results demonstrate the potential of Ca_8−xSr_xZnEu(PO₄)₇ phosphates for bioimaging and bone healing control. Full article