Search Results (162)

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

Diabetes mellitus is a serious public health problem, mainly due to the difficulty in healing chronic wounds, which present an inflammatory response for long periods of time and are more vulnerable to infections. Hydrogels are a promising therapeutic solution due to their biocompatibility, biodegradability, and ability to allow controlled release of therapeutic agents. The addition of bioactive glasses doped with therapeutic ions to hydrogels can also provide specific biological responses to the system and thus improve tissue regeneration. In this study, a hydrogel based on carboxymethylcellulose and polyethylene glycol with different degrees of crosslinking and enriched with 10% by weight of CeO₂-doped Bioglass 45S5 was developed. Structural, morphological, mechanical, and biological characterizations were performed on bioactive glass, hydrogels, and hydrogels enriched with bioactive glass. Structural analyses confirmed the preservation of the typical amorphous structure of Bioglass 45S5, even after the incorporation of 5% molar CeO₂, as well as the effectiveness of the polymer matrix crosslinking process. Structural analyses demonstrated the preservation of the typical amorphous structure of Bioglass 45S5, even after the incorporation of 5 mol% CeO₂, as well as the effectiveness of the polymer matrix cross-linking process. The hydrogels exhibited distinct behaviours in terms of water absorption and degradation, showing that the sample with the lowest concentration of crosslinkers and bioactive glass allowed for a higher expansion rate and a higher degradation rate. The hydrogel with 10 wt% BG did not compromise cell viability and showed structural integrity after being subjected to cyclic flexible deformations, indicating its safety and suitability for use in tissue engineering. Full article

Bioactive glasses (BGs) are promising materials for enamel remineralization and caries management due to their ion-releasing ability and capacity to promote apatite formation. However, their clinical translation remains limited. Conventional BGs, such as 45S5, exhibit excellent bioactivity but are mechanically weak, prone to rapid ion burst release, and lack long-term stability. Recent advances—including secondary oxide incorporation (e.g., B₂O₃, ZnO), polymer–glass hybrids, and nanostructured systems like mesoporous BGs and RegeSi have improved reactivity, mechanical performance, and remineralization depth, though their durability under oral conditions is not yet established. BGs also display antibacterial activity by elevating local pH and releasing ions that inhibit cariogenic bacteria, but their broader ecological impact on the oral microbiome remains poorly understood. Emerging approaches such as halogen-modified BGs, particularly fluoride- and chloride-doped formulations, show dual benefits for remineralization and antimicrobial action, though supporting evidence is largely confined to in vitro studies. The absence of standardized protocols for assessing remineralization, ion release, and biofilm interaction further complicates cross-study comparisons and slows clinical adoption. Future progress will require interdisciplinary collaboration, standardized evaluation methods, and rigorous clinical validation to ensure that next-generation BGs can be safely and effectively integrated into dental practice. Full article

Estrogen deficiency is a primary cause of osteoporosis, compromising bone mineral density that may impair peri-implant healing. Given the compromised bone environment associated with estrogen deficiency, strategies such as particle reduction via sonochemistry are promising approaches to enhance regenerative outcomes. However, its effects in promoting bone formation remain insufficiently explored. Therefore, this study evaluated the potential of two sonicated biomaterials to improve peri-implant repair in ovariectomized rats. Fifty female rats were allocated into five groups: blood clot (CLOT), Biogran^® (BGN), sonicated Biogran^® (BGS), Bio-Oss^® (BON), and sonicated Bio-Oss^® (BOS). Tibial peri-implant defects were created 30 days after ovariectomy and analyzed 28 days later by removal torque, microcomputed tomography, and confocal microscopy. BGS exhibited the highest removal torque (6.28 Ncm), followed by BON (5.37 Ncm), BOS (3.92 Ncm), BGN (3.15 Ncm), and CLOT (2.58 Ncm). Micro-CT revealed bone volume fraction (BV/TV) values of 8.07% (CLOT), 6.47% (BOS), 6.02% (BGS), 5.55% (BGN), and 2.84% (BON). For the trabecular number (Tb.N), BGS (1.11 mm⁻¹) showed a significant increase compared with BGN (0.69 mm⁻¹), p < 0.05. These findings show that sonochemically modified bioactive glass improves mechanical stability and trabecular microarchitecture under estrogen-deficient conditions. However, further studies are needed to standardize sonication parameters for different biomaterials and expand their translational applicability. Full article

Alginate-hydroxyapatite (AL) scaffolds modified with fibronectin (FN) or bioactive glass (BGMS10) have recently been characterized for their physicochemical properties and proposed as promising candidates for bone regeneration. Here, we present their first systematic biological evaluation, focusing on adhesion, proliferation, osteogenic differentiation, and in vivo host response. We compared FN-, BG-, and unmodified AL scaffolds using an immortalized mesenchymal stromal cell line (M-SOD) and primary human bone marrow-derived (BM-MSCs) and adipose-derived stromal cells (ASCs). FN scaffolds enhanced initial adhesion across all cell types and supported proliferation in M-SODs, but primary BM-MSCs and ASCs showed minimal expansion, regardless of scaffold type. BG scaffolds promoted expression of late-stage osteogenic markers in BM-MSCs, consistent with their ion release profile, but had limited impact on ASCs. In vivo subcutaneous implantation of acellular scaffolds in nude mice revealed robust host cell infiltration and extracellular matrix deposition across all scaffold types, confirming biocompatibility and integration. However, vascularization remained limited and did not differ substantially between formulations. Together, these findings highlight a critical discrepancy between immortalized and primary stromal cell responses to scaffold cues, underscoring the choice of cell source when evaluating the biocompatibility of a novel scaffold. At the same time, the effective in vivo integration observed across scaffold types emphasizes the importance of host tissue responses for translational evaluation of functional biomaterials. Full article

The development of bioactive glasses (BGs) and ceramics, such as β-Tricalcium phosphate (β-TCP), Hydroxyapatite (HAp), and apatite-wollastonite (A-W), has revolutionized regenerative medicine (RM), offering innovative solutions for bone and tissue repair, due to the ability of these materials to bond with living bone tissue. Despite significant advancements, evaluating the bioactivity and biological responsiveness of these biomaterials remains a critical challenge. This review provides a comprehensive synthesis of the available methodologies, critically analyzing their advantages, disadvantages, and the possible gap between in vitro and in vivo assessments, including false positives and false negatives. Classical immersion tests techniques for bioactivity evaluation in simulated physiological solutions, such as simulated body fluid (SBF), Tris-buffer (TRIS), or phosphate-buffered saline (PBS) solutions, are discussed, along with the more innovative Simulated Wound Fluid (SWF). Additionally, traditional standardized methods, such as MTT, BrdU, EdU, and XTT, as well as emerging methods like qPCR and immunocytochemistry, used to study cellular behavior, proliferation, adhesion, and differentiation, are compared. Staining assays, including crystal violet, neutral red, and alizarin red, have also been investigated for their effectiveness in evaluating cellular adhesion and quantification. Notably, while all techniques have shown promise in studies involving BGs and ceramics, a multi-parametric approach remains the most reliable strategy for assessing bioactivity and biological responsiveness, highlighting the need for comprehensive studies to validate the results. Finally, the choice between static and dynamic approaches represents a further critical issue, as it significantly affects assay outcomes. Full article

Osteoarthritis (OA), the most common joint disease, is marked by cartilage degradation and chronic inflammation. While 45S5-bioactive glass (45S5-BG) is well-established in bone regeneration and has been suggested to exert immunomodulatory effects, its impact on OA chondrocytes remains largely unexplored. Therefore, this in vitro study investigated the effects of 45S5-BG microparticles (0.125 mg/mL) on chondrocytes derived from OA patients, evaluating its therapeutic potential in OA. Chondrocytes were cultured with or without 45S5-BG for 1 and 7 days. Gene expression of cartilage markers, cytokines, matrix metalloproteinases (MMPs), and toll-like receptors (TLRs) was analyzed by qPCR. Protein levels were assessed by ELISA. 45S5-BG stimulation significantly altered chondrocyte activity, inducing upregulation of IL-6, IL-1β, TNF-α, MMP-1/-3/-13, and TLR4. Expression of ACAN and COL2A1 was reduced, while COL10A1—a marker of chondrocyte hypertrophy—was significantly increased at day 1. These findings show a catabolic and pro-inflammatory shift in chondrocyte phenotype upon 45S5-BG exposure, showing no therapeutic benefit of 45S5-BG on OA chondrocytes. However, considering the pronounced effects on chondrocyte activity and the well-established bioactivity and biocompatibility of 45S5-BG, our findings suggest that modified BG formulations could be developed to enhance chondroprotective and anti-inflammatory properties, warranting further investigation in co-culture and in vivo models. Full article

Background/Objectives: Gamma irradiation is a promising terminal sterilization method for nanoparticle-based biomedical systems. However, its potential effects on the physicochemical properties and biological performance of multifunctional nanomaterials must be carefully evaluated. This study aimed to assess the structural integrity, sterility, and cytocompatibility of magnetic nanoparticles (MNPs) and bioactive-glass-coated magnetic nanoparticles (MNPBGs), both based on magnetite (Fe₃O₄), after gamma irradiation. Methods: MNPs and MNPBGs were synthesized and subjected to gamma irradiation at 25 kGy, with additional doses explored in preliminary evaluations. Physicochemical characterizations were performed using XRD, TEM, SAED, and Raman spectroscopy. FTIR analyses were conducted on bioactive glass (BG) controls without magnetite. Sterility was evaluated via microbiological assays. Cytocompatibility and nitric oxide (NO) production were assessed using RAW 264.7 macrophages and Saos-2 osteosarcoma cells. Prussian blue staining was used to evaluate cellular uptake. Results: Gamma irradiation preserved the crystal structure, morphology, and size distribution of the nanoparticles. FTIR revealed only minor changes in the silicate network of BG, such as reduced intensity and slight shifting of Si-O-Si and Si-O-NBO bands, indicating limited radiation-induced structural rearrangement without affecting the material’s stability or cytocompatibility. Microbiological assays confirmed complete inhibition of microbial growth. All irradiated samples exhibited high cytocompatibility, with MNPBGs demonstrating enhanced biological responses. Notably, MNPBGs induced a more pronounced NO production in macrophages. Cellular uptake of nanoparticles by Saos-2 cells remained unaffected after irradiation. Conclusions: Gamma irradiation at 25 kGy is an effective sterilization strategy that maintains the structural and functional integrity of MNPs and MNPBGs. These findings support their safe use in sterile biomedical applications, particularly for bone-related therapies involving immunomodulation and drug delivery, with potential relevance for cancer treatment strategies such as osteosarcoma. Full article

Bioactive glass materials have been used for decades in orthopedic surgery, traumatology, and oral and maxillofacial surgery to repair bone defects. This study aimed to evaluate in vitro the survival and proliferation of MG63 human osteosarcoma-derived cells on S53P4 bioactive glass (BonAlive^® granules). Microscopic visualization was performed to directly observe the interactions between the cells and the material. Osteoblast-like cells were examined on non-adherent test plates, on tissue culture (TC)-treated plates and on the surface of the bioglass to assess the differences. Cell survival and proliferation were monitored using a CCK-8 optical density assay. Comparing the mean OD of MG63 cells in MEM on TC-treated plates with cells on BG, we detected a significant difference (p < 0.05), over each time of observation. The sustained cell proliferation confirmed the non-cytotoxic property of the bioglass, as the cell number increased continuously at 48, 72, 96, and 168 h and even did not plateau after 168 h. Since the properties of bioglasses can vary significantly depending on their composition and environment, a thorough characterization of their biocompatibility is crucial to ensure their effective and appropriate application—for example, during hip and knee prosthesis insertion. Full article

UV-cured methacrylated chitosan (MCHIT) hydrogels were achieved in the presence of silanised tellurium-doped silica bioactive glass (BG-Te-Sil) to produce an antimicrobial and osteoconductive scaffold for tissue engineering applications. Methacrylation of chitosan enabled efficient crosslinking, and the curing process was evaluated by means of Fourier-transform infrared spectroscopy (FTIR) and photorheology analyses. Compressive testing on crosslinked hydrogels showed that the silanised, bioactive, doped glass increased the hydrogel’s elastic modulus by up to 200% compared to unreinforced controls. Antibacterial assays against Staphylococcus aureus ATCC 43300 revealed a significant (p < 0.05) reduction in bacterial metabolic activity for hydrogels containing 50 wt% of the Te-doped bioactive glass. In vitro cytocompatibility with human bone-marrow mesenchymal stem cells demonstrated sustained viability and uniform distribution at 72 h (live/dead staining, AlamarBlue). Under H₂O₂-induced oxidative stress, reinforced hydrogels downregulated pro-inflammatory genes (TNF-α, IFN-γ, IL-1β, and PGES-2). These results suggest that the presence of the silanised bioactive glass can significantly enhance mechanical stability, antibacterial properties, and anti-inflammatory responses without affecting cytocompatibility, making these hydrogels promising for tissue engineering applications. Full article

Direct ink writing (DIW) is an attractive, extrusion-based, additive manufacturing method for fabricating scaffold structures with controlled porosity using custom composite inks. Polycaprolactone–bioactive glass (PCL-BG) inks have gained attention for bone applications, but optimizing the formulation and fabrication of PCL-BG-based inks for improved printability and desired mechano-biological properties remains a challenge. This study employs a two-step design to systematically evaluate the effect of three factors in terms of PCL-BG composite printability and mechano-biological properties: ink preparation (acetone or dichloromethane (DCM) as the solvent, and mechanical compounding), the extrusion temperature (90 °C, 110 °C, and 130 °C), and the BG content (0%, 10%, and 20% BG). Pure PCL was used as the control. Rheological, calorimetric, and thermo-gravimetric analyses were conducted before printing. Cylindrical scaffolds and solid wells were printed to evaluate the printability, mechanical properties, and cytocompatibility. The scaffold porosity and pore size were carefully examined. Mechanical tests demonstrated that composite formulations with added BG and higher printing temperatures increased the elastic modulus and yield strength. However, PCL-DCM-BG combinations exhibited increased brittleness with higher BG content. Despite concerns about the toxic solvent DCM, the cytocompatibility was comparable to pure PCL for all ink preparation methods. The results suggest that the interaction between the ink preparation solvent, the BG content, and the printing temperature is critical for material design and fabrication planning in bone tissue engineering applications, providing insights into optimizing PCL-BG composite ink formulations for 3D printing in bone tissue engineering. Full article

Bioactive glass (BG) is a promising material known for its osteogenic, osteoinductive, antimicrobial, and angiogenic properties. For this reason, melt-quench-derived BG powders embedded into composite electrospun poly(ε-caprolactone) (PCL) mats represent an interesting option for the fabrication of bioactive scaffolds. However, incorporating BG into nano-/micro-fibers remains challenging. Our research focused on integrating two BG compositions into the mat structure: 45S5 and 45S5_MS (the former being a well-known, commercially available BG composition, and the latter a magnesium- and strontium-enriched composition based on 45S5). Both BG types were added at concentrations of 10 wt.% and 20 wt.%. A careful grinding process enabled effective dispersion of BG into a PCL solution, resulting in fibers ranging from 500 nm to 2 µm in diameter. The mats’ mechanical properties were not hindered by the inclusion of BG powder within the fibrous structure. Furthermore, our results indicate that BG powders were successfully incorporated into the scaffolds, not only preserving their properties but potentially enhancing their biological performance compared to unloaded PCL electrospun scaffolds. Our findings indicate proper cell differentiation and proliferation, supporting the potential of these devices for tissue regeneration applications. Full article

Delayed or non-healing of bone defects in an aging, multi-morbid population is still a medical challenge. Current replacement materials, like autografts, are limited. Thus, artificial substitutes from biodegradable polymers and bioactive glasses (BGs) are promising alternatives. Here, novel cerium-doped mesoporous BG microparticles (Ce-MBGs) with different cerium content were included in photocrosslinkable, methacrylated gelatin (GelMA) for promoting cellular functions of human mesenchymal stem cells (hBMSCs). The composites were studied for intrinsic morphology and Ce-MBGs distribution by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). They were gravimetrically analyzed for swelling and stability, compressive modulus via Microsquisher^® and bioactivity by Fluitest^® calcium assay and inductively coupled plasma-optical emission spectrometry (ICP-OES), also determining silicon and cerium ion release. Finally, seeding, proliferation, and differentiation of hBMSCs was investigated. Ce-MBGs were evenly distributed within composites. The latter displayed a concentration-dependent but cerium-independent decrease in swelling, while mechanical properties were comparable. A MBG type-dependent bioactivity was shown, while an enhanced osteogenic differentiation of hBMSCs was achieved for Ce-MBG-composites and related to different ion release profiles. These findings show their strong potential in promoting bone regeneration. Still, future work is required, e.g., analyzing the expression of osteogenic genes, providing further evidence for the composites’ osteogenic effect. Full article

Critical-size bone defects do not heal spontaneously and require external support, making bone regeneration a central challenge in tissue engineering. Polymeric/ceramic composite scaffolds offer a promising approach to mimic the structural and biological properties of bone. In this study, we aimed to evaluate the effect of different doping oxides in bioactive glass (BG) on the performance of polycaprolactone (PCL)-based composite scaffolds for bone tissue engineering applications. Composite scaffolds were fabricated using solvent casting, hot pressing, and salt-leaching techniques, combining PCL with 25 wt% of BG or doped BG containing 4 mol% of tantalum, zinc, magnesium, or niobium oxides, and 1 mol% of copper oxide. The scaffolds were characterized in terms of morphology, mechanical properties, and in vitro biological performance. All scaffolds exhibited a highly porous, interconnected structure. Mechanical compression tests indicated that elastic modulus increased with ceramic content, while doping had no measurable effect. Cytotoxicity assays confirmed biocompatibility across all scaffolds. Among the tested materials, the Zn-doped BG/PCL scaffold uniquely supported cell adhesion and proliferation and significantly enhanced alkaline phosphatase (ALP) activity—an early marker of osteogenic differentiation—alongside the Nb-doped scaffold. These results highlight the Zn-doped BG/PCL composite as a promising candidate for bone regeneration applications. Full article

Injuries characterized by significant loss of skeletal muscle tissue volume, known as volumetric muscle loss (VML), lead to substantial impairment in functional capabilities. Natural repair processes and existing medical interventions fall short of fully restoring function post-VML. Despite progress in the VML field, there is an unsatisfactory success rate, donor site morbidity, and inefficient reconstruction of lost muscle tissue. This leads to persistent strength and functional deficits, impacting the quality of life for VML patients. In recent years, studies have explored the potential of bioactive glasses (BGs) as crucial materials in regenerating tissues beyond the skeletal system. BG, used mainly in bone engineering, can aid muscle repair by releasing ions like calcium and phosphate to stimulate cellular response. However, current BG composites struggle to match the mechanical properties of soft tissues, limiting seamless healing. This review summarizes recent advances in various BG structures studied for skeletal muscle tissue regeneration. Full article