Search Results (65)

The development of multifunctional biomaterials for bone repair requires precursors that combine bioactivity, moderate antimicrobial growth-inhibitory effect, and imaging. This study demonstrates the multifunctional versatility of a single family of rare-earth-doped β-tricalcium phosphates (β-TCPs), Ca₉Eu(PO₄)₇ and Ca₉Dy(PO₄)₇, across three distinct formats: bioactive thin films (for implant coatings), brushite cements (for injectable bone fillers), and radiopaque PMMA bone composites (for load-bearing applications). This work serves as a proof-of-concept that the same doped phosphate precursors can address different clinical needs while retaining bioactivity, antimicrobial properties, and radiopacity. The phosphate precursors were synthesized via solid-state reaction. Pulsed laser deposition (PLD) was used to form amorphous, dense, and crack-free coatings, which exhibited excellent in vitro bioactivity through the rapid dissolution–reprecipitation of a carbonated apatite layer in simulated body fluid. The brushite-based bone cements were produced from doped β-TCPs. These cements demonstrated high cytocompatibility with mesenchymal stromal cells (>89% viability) and significantly enhanced osteogenic differentiation with antimicrobial activity against common pathogens (S. aureus, E. coli, P. aeruginosa). Furthermore, incorporation of these phosphates as fillers into PMMA bone cement resulted in a homogeneous particle distribution with reduced agglomeration compared to undoped β-TCPs, achieving clinically relevant radiopacity values (913 ± 22.4 HU for Dy-doped sample). Post-mortem studies by the CT method were performed on the vertebrae with PMMA–phosphate composites and brushite cements. It was shown that brushite cement in ovine lumbar vertebrae defects exhibited the highest radiopacity (1450–1550 ± 25 HU). The findings establish rare-earth-doped β-TCP as a unified multifunctional precursor that imparts bioactivity, the ability to support in vitro mineralization, antimicrobial properties, and enhanced radiopacity to thin films, phosphate cements, and polymer composite materials. Full article

The design of implant surfaces that support bone integration while limiting bacterial colonization remains a central challenge in biomaterials science and engineering. In this work, zinc-doped biomimetic calcium phosphate (CaP-Zn) coatings were fabricated on Ti6Al4V through surface activation followed by deposition in supersaturated simulated body fluid (SBF). Acid and alkali–calcium treatments produced a porous, calcium-rich interface that enabled the uniform formation of apatite-like CaP layers. Zinc incorporation was achieved without suppressing the formation of CaP phases and led to systematic changes in coating microstructure and surface chemistry. Spectroscopic and structural analyses indicated Zn incorporation within the CaP matrix, consistent with partial Ca²⁺ substitution and its association with poorly crystalline domains. These features promoted controlled ionic release and localized dissolution–reprecipitation behavior. Antibacterial testing against Streptococcus mutans revealed a clear Zn-dependent reduction in bacterial viability, while cytocompatibility remained within acceptable limits at moderate Zn levels. Finally, the coatings combine intrinsic bioactivity with ion-mediated antibacterial functionality, offering a multifunctional surface strategy for advanced titanium-based implants. Full article

Bioactive glass (BAG) S53P4 is a clinically approved bone substitute with antibacterial, osteoconductive and osteostimulatory properties. Its antibacterial effect is associated with ion release, local pH elevation and osmolality, but the precise biochemical and biophysical mode-of-action is unclear. This study investigates the antibacterial mechanism of BAG S53P4 eluates. BAG eluates, collected at 2, 4, 8, and 24 h, eradicated Staphylococcus aureus. Elemental analysis revealed an early increase in concentrations of Si and Na, a later rise in Ca, depletion of P over time and rapid loss of Mg. Membrane disturbances occurred within 5 min, evident by permeability for SYTOX, aligning with time-kill kinetics for S. aureus and Bacillus subtilis. In B. subtilis, 2h-BAG-eluate induced rapid delocalization of marker proteins for cell division and DNA repair, signaling membrane potential collapse and nucleoid condensation. Transcriptomics revealed early transcription remodeling reflecting ionic and energetic imbalance, including disruption of central metabolism, redox homeostasis, and translational stability. Scanning electron microscopy revealed severe cell surface damage and particulate deposits on S. aureus. Transmission electron microscopy showed cell envelop disruptions and cytoplasmic leakage. Energy dispersive X-ray analysis identified Si on bacterial cell surface at 4 h and intracellular accumulation in punctured, empty cells at 24 h. Overall, BAG ionic dissolution products kill bacteria through a stepwise mechanism involving membrane damage, protein delocalization and metabolic impairment, accompanied by Si deposition on bacterial surfaces and loss of Mg. This finally leads to cell wall degradation, cytoplasmic content leakage and further Si deposition on the cells and inside cell ghosts. Full article

Nanostructured calcium phosphate-based (CaP) biocomposites have proven to be ideal candidates for the creation of multifunctional systems with applications in biomedicine. This review presents a critical and integrative overview of recent advances in the synthesis of CaP nanocomposites with applications in bone tissue regeneration. An analysis of calcium phosphate-based nanocomposites is thus provided by correlating their composition, synthesis routes and biological properties, guiding the rational development of next-generation biomaterials for bone tissue engineering. The first section presents calcium phosphates, such as hydroxyapatite (HAp) or β-tricalcium phosphate (β-TCP), used in the preparation of nanocomposite materials. Next, the main biocomposite materials are analyzed as a result of the functionalization of calcium phosphates by metal ion substitutions or by the addition of polymers, bioglass or metal additives. Thus, biomaterials with excellent properties in applications such as tissue engineering have been obtained. The synergistic effect of materials in the composition of biocomposites favored the improvement of properties such as bioactivity, mechanical strength, antimicrobial activity, structure and porosity. Beyond classical osteoconductivity, CaP-based nanocomposites demonstrate a broad spectrum of biological activities like immunomodulatory effects, pro-healing signaling, anti-inflammatory pathways, antibacterial and antifungal mechanisms, and capabilities for precise drug delivery or theranostic applications. Full article

Tetracyclines are broad-spectrum bacteriostatic agents with well-established antimicrobial efficacy and a shared core chemical structure, differentiated by distinct functional substitutions across generations. Beyond their antibacterial action, tetracyclines also exhibit pleiotropic biological effects, including modulation of bone metabolism. Nevertheless, the selection of agents and dosing for local bone applications remains largely empirical. Therefore, this study compares the tissue-level osteogenic potential of four tetracyclines from distinct generations using a translational ex vivo embryonic chick femur model. Organotypic femur cultures were maintained for 11 days and exposed to tetracycline (TC), doxycycline (DC), minocycline (MC), or sarecycline (SC), at 1 and 10 µg/mL, concentrations corresponding to clinically relevant local and systemic exposures. Osteogenic outcomes included microcomputed tomography, histological analyses, and quantitative gene expression. At 1 µg/mL, tetracyclines promoted osteogenic effects, increasing collagen deposition by approximately 30%, enhancing matrix maturation by 100%, stimulating tissue mineralization by 20–50%, and upregulating osteogenic marker expression, with TC exhibiting weaker activity. At 10 µg/mL, osteogenic stimulation was notably reduced across all groups. This study provides the first tissue-level, head-to-head comparison of four tetracyclines and their effects on bone biology. The findings indicate that tetracycline-induced osteogenic activity is both agent-specific and concentration-dependent, underscoring the importance of using lower doses to maximize osteogenic responses and supporting the preferential use of DC, MC, and SC in bone regeneration and adjunctive therapeutic applications. Full article

During recent decades, bone cancer-related diseases have remained hard to treat because of poor diagnosis, systemic toxicity, and restricted conventional treatments. Hence, the fabrication of functionalised nanoparticles offers a promising alternative by limiting side effects and improving therapeutic outcomes. In this study, zinc-substituted hydroxyapatite (Zn-HA) nanoparticles were fabricated from biogenic tuna fish bone waste via a thermal decomposition method and subsequently functionalised with Catharanthus roseus (CR) flower extract to synthesise a Zn-HA/CR nanocomposite. Structural and compositional characterisations verified Zn ions incorporation into the HA lattice and efficient CR-derived phytochemical functionalisation without altering the hexagonal HA phase. Compared to pure hydroxyapatite, the Zn-HA/CR nanocomposite exhibited improved surface morphology, enhanced swelling behaviour and degradation, and increased microhardness. The nanocomposite demonstrated significantly enhanced antibacterial activity against Staphylococcus aureus and Escherichia coli. The Zn-HA/CR nanocomposite also showed strong, dose-dependent antioxidant activity in DPPH assays. Furthermore, in vitro cytotoxicity studies using MG-63 (HOS) osteosarcoma cancer cells revealed that the proposed nanocomposite leads to pronounced morphological alterations and reduced cell viability. The prepared Zn-HA/CR nanocomposite would be a potential nanocomposite for enhanced antioxidant and anticancer activity, which highlights this composite as a multifunctional biomaterial platform for therapeutic applications. Full article

The development of effective bone substitutes remains a central goal in regenerative medicine. In this study, lithium-modified bioglass-ceramics based on the 47.5S5 silicate oxide system were synthesized using the sol–gel method, followed by calcination and axial pressing to form cylindrical samples. These materials were sintered at 700 and 800 °C and subsequently examined to evaluate their structural, mechanical, and biological performance. Structural and microstructural analyses confirmed the presence of crystalline phases such as combeite (Na₆Ca₃Si₆O₁₈), NaLiSiO₄, Li₂SiO₃, and calcium silicates, indicating the successful incorporation of lithium within the glass-ceramic network. The bioceramics exhibited improved densification, deformability, and compressive strength with increasing sintering temperature. In vitro degradation in simulated body fluid revealed a consistent increase in mass loss with higher lithium content, suggesting enhanced resorbability linked to lithium oxide. Antibacterial testing indicated moderate antimicrobial activity, with slightly better results observed at higher sintering temperatures. Cell viability assays further supported the materials cytocompatibility. Taken together, these findings suggest that lithium substitution contributes positively to both mechanical robustness and biological behaviour, positioning these ceramics as promising bioresorbable bone substitutes with controlled degradation, suitable for bone tissue engineering where durability, bioactivity, and antimicrobial function are required. 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

Biodegradable magnesium (Mg) alloys hold promising application prospects in the field of guided bone regeneration (GBR) membranes, particularly for oral and maxillofacial applications. However, their corrosion resistance requires further improvement. Additionally, Mg alloys are susceptible to bacterial infection upon implantation, while copper (Cu) is known for its excellent antibacterial properties. Introducing Cu into the micro-arc oxidation (MAO) coating can enhance both the corrosion resistance and antibacterial performance of Mg alloys. However, the sealing effect of such coatings remains suboptimal. Hydroxyapatite (HA), which possesses outstanding bioactivity, is a promising bone substitute material. This study investigates the influence of HA content on the microstructure, corrosion resistance, cytotoxicity, and antibacterial properties of Cu-containing MAO coatings. The results demonstrate that as the HA concentration increases, the corrosion resistance of the composite coating is significantly enhanced. The corrosion rate decreased from 0.32 mm/y for the untreated MAO coating to 0.27 mm/y and 0.23 mm/y for the HA-treated samples with EDTA–Ca concentrations of 125 mmol/L and 175 mmol/L, respectively. Cytotoxicity assessment indicates that the incorporation of an HA layer significantly improves cell compatibility compared to the bare MAO coating. However, the enhanced corrosion resistance provided by the denser HA layer (at 175 mmol/L EDTA–Ca) unfortunately acts as a barrier, limiting the release of antibacterial Cu²⁺. Among the coatings tested, the one with 125 mmol/L EDTA–Ca exhibited the best overall performance, demonstrating good corrosion resistance, cytocompatibility, and effective antibacterial properties. Full article

Applying therapeutic elements to prevent injury from potential infections is a promising avenue in the development of novel bone substitutes; however, achieving controllable delivery of therapeutic ions is crucial to realizing their expected functions. In this study, a Ag nanoparticle core wrapped in an MSN shell was successfully synthesized using a one-pot sol–gel process. Subsequently, the produced Ag@MSN was functionalized with amino and carboxylic groups. The experimental results indicated that these core–shell-structured Ag@MSN spheres had a uniform size of ~60 nm and a specific area of 904.6 m²/g. Their release profiles, influenced by different surface charges, were investigated, with the aim of achieving sustainable release of Ag ions. The concentration-dependent biological effects of Ag@MSNs, including their anti-infection properties and biocompatibility, were comprehensively characterized in vitro, considering their potential for use as bioactive bone substitutes. Functionalized mesoporous silica nanoparticles significantly enhanced the sustained release profile of silver ions, achieving a cumulative release efficiency greater than 50% within 24 h. These nanoparticles also demonstrated exceptional antibacterial efficacy, with an inhibition rate surpassing 98% at a concentration of 30 μg/mL, while concurrently maintaining cell viability above 88%, indicating high biocompatibility. We achieved our goal of effectively decreasing the burst release of Ag to satisfy the intrinsic need for long-term resistance to bacteria in bone substitutes and stimulate osteoblast proliferation. Full article

Bone tissue restoration requires biomaterials, which combine osteoinductivity and the capability to prevent surgical site infections. Magnesium-substituted biphasic calcium phosphate (Mg-BCP) represents a promising solution, as magnesium substitution increases the biodegradation rate of calcium phosphate ceramics and provides inherent antibacterial properties. This study aimed to achieve wet precipitation synthesis of magnesium-substituted (1–10 mol%) biphasic calcium phosphate and to evaluate its drug delivery potential and antibacterial performance. Porous Mg-BCP granules were fabricated via the gelation of Mg-BCP suspension in sodium alginate followed by polymer removal. Drug delivery potential was evaluated using methylene blue as a model compound, with methylcellulose encapsulation implemented to ensure prolonged release. Magnesium content directly ruled the phase composition: low concentrations (1%) favored hydroxyapatite phase prevalence, while higher concentrations led to the β-tricalcium phosphate formation. Further assessment of drug delivery potential revealed that direct drug loading resulted in burst release, whereas methylcellulose encapsulation successfully enabled prolonged drug delivery. Mg-5BCP formulation demonstrated significant antimicrobial activity with growth inhibition of 17.7 ± 4.1% against C. albicans, 20.8 ± 7.0% against E. faecalis, and 12.9 ± 7.5% against E. coli. Therefore, Mg-5BCP–methylcellulose composite granules present a versatile platform for antibacterial drug delivery for bone tissue engineering applications. Full article

Novel three-dimensional porous composites of alginate–pectin (A/P) with zinc- or manganese-substituted hydroxyapatites (A/P-ZnHA and A/P-MnHA) were synthesized via lyophilization and calcium cross-linking. Powder X-ray diffraction and infrared spectroscopy analyses confirmed single-phase apatite formation (crystallite sizes < 1 µm), with ZnHA exhibiting lattice contraction (*c*-axis: 6.881 Å vs. 6.893 Å for HA). Mechanical testing revealed tunable properties: pristine A/P sponges exhibited an elastic modulus of 4.7 MPa and a tensile strength of 0.10 MPa, reduced by 30–70% by HA incorporation due to increased porosity (pore sizes: 112 ± 18 µm in the case of MnHA vs. 148 ± 23 µm-ZnHA). Swelling capacity increased 2.3–2.8-fold (125–155% vs. 55% for A/P), governed by polysaccharide interactions. Scanning electron microscopy investigation showed microstructural evolution from layered A/P (<100 µm) to tridimensional architectures with embedded mineral particles. The A/P-MnHA composites demonstrated minimal cytotoxicity for the NCTC cells and good viability of dental pulp stem cells, while A/P-ZnHA caused ≈20% metabolic suppression, attributed to hydrolysis-induced acidification. Antibacterial assays highlighted A/P-MnHA′s broad-spectrum efficacy against Gram-positive (Bacillus atrophaeus) and Gram-negative (Pseudomonas protegens) strains, whereas A/P-ZnHA targeted only the Gram-positive strain. The developed composite sponges combine cytocompatibility and antimicrobial activity, potentially advancing osteoplastic materials for bone regeneration and infection control in orthopedic/dental applications. 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

Background: Pathological bone fracturing is an escalating problem driven by increasing aging and obesity. Bioceramics, particularly tricalcium-phosphate-based materials (TCP), are renowned for their exceptional biocompatibility, osteoconductivity, and ability to promote biomineralization. In the present study, we designed and characterized TCP porous granules doped with strontium (Sr) and copper (Cu) (CuSr TCP). Sr²⁺ ions were selected as Sr plays a crucial role in early bone formation, osteogenesis, and angiogenesis; Cu²⁺ ions possess antibacterial properties. Materials: The synthesized CuSr TCP granules were characterized by X-ray diffraction. Cytotoxicity and cell proliferation analyses’ assays were performed through the lactate dehydrogenase (LDH) activity and CCK-8 viability tests in rat bone marrow-derived mesenchymal stem cells (BM-MSCs). Hemolytic activity was carried out with human red blood cells (RBCs). Early and late osteogenesis were assessed with alkaline phosphatase (ALP) and Alizarin Red S activity in human osteoblast progenitor cells and rat BM-MSCs. The influence of CuSr TCP on angiogenesis was investigated in human umbilical vein endothelial cells (HUVECs). Results: We have demonstrated that media enriched with CuSr TCP in concentrations ranging from 0.1 mg/mL to 1 mg/mL were not cytotoxic and did not significantly affect cell proliferation rate motility. Moreover, a concentration of 0.5 mg/mL showed a 2.5-fold increase in the migration potential of BM-MSCs. We also found that CuSr TCP-enriched media slightly increased early osteogenesis. We also found that Sr and Cu substitutions in TCP particles significantly enhanced the measured angiogenic parameters compared to control and unsubstituted TCP granules. Conclusion: Our results demonstrate that TCP porous granules doped with Sr and Cu are biocompatible, promote osteodifferentiation and angiogenesis, and could be recommended for further in vivo studies. Full article

Bone defects are commonly addressed with bone graft substitutes; however, surgical procedures, particularly for open and complex fractures, may pose a risk of infection. As such, a course of antibiotics combined with a drug carrier is often administered to mitigate potential exacerbations. This study involved the preparation and modification of emulsified (Em) crosslinking-gelatin (gel) microspheres (m-Em) to reduce their toxicity. The antibiotic gentamicin was impregnated into gel microspheres (m-EmG), which were incorporated into calcium phosphate bone cement (CPC). The study investigated the effects of m-EmG@CPC on antibacterial activity, mechanical properties, biocompatibility, and proliferation and mineralization of mouse progenitor osteoblasts (D1 cells). The average size of the gel microspheres ranged from 22.5 to 16.1 μm, with no significant difference between the groups (p > 0.05). Most of the oil content within the microspheres was transferred through modification, resulting in reduced cytotoxicity. Furthermore, antibiotic-impregnated m-EmG did not compromise the intrinsic properties of the microspheres and exhibited remarkably antibacterial effects. After combining with CPC (m-EmG@CPC), the microspheres did not significantly hinder the CPC reaction and produced the main product, hydroxyapatite (HA). However, the compressive strength of the largest microsphere content of 0.5 wt.% m-EmG in CPC decreased significantly from 59.8 MPa of CPC alone to 38.7 MPa of 0.5m-EmG@CPC (p < 0.05). The 0.5m-EmG@CPC composite was effective against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) in drug release and antibacterial tests. Compared with m-EmG alone, the 0.5m-EmG@CPC composite showed no toxicity to mouse fibroblast cells (L929). Additionally, the proliferation and mineralization of mouse osteoblastic osteoprogenitor cells (D1 cells) did not have a negative impact on the 0.5m-EmG@CPC composite over time in culture compared with CPC alone. Results suggest that the newly developed antibacterial 0.5m-EmG@CPC composite bone cement did not negatively affect the performance of osteoprogenitor cells and could be a new option for bone graft replacement in surgeries. Full article