Search Results (506)

Mesoporous bioactive glasses (MBGs) represent a significant advancement in bioactive glass technology, combining the well-established osteoconductive and osteoinductive properties of traditional bioactive glasses with the structural precision provided by highly ordered mesoporosity. Their characteristic architecture, defined by uniform pores typically ranging from a few to several tens of nanometers and exceptionally high surface areas reaching several hundred m²/g, enables enhanced drug-loading capacity, controlled therapeutic ion release, and accelerated tissue regeneration. In this work, we emphasize how the synthesis of these materials is predominantly governed by structure-directing agents, which critically influence the pore size, mesophase ordering, surface area, and structural stability. Additionally, we discuss how compositional tailoring, particularly through therapeutic ion doping with elements such as Sr, Cu, Zn, or B, can impart osteogenic, angiogenic, antibacterial, or antioxidant functionalities. Moreover, we illustrate how these functionalities can be further expanded and enhanced by employing a comprehensive suite of characterization tools to establish robust correlations between synthesis parameters, mesostructural features, and biological performance. Improving the above functionalities enables the MBGs to exhibit exceptional versatility across biomedical applications, notably in bone tissue engineering (as hierarchical or composite scaffolds), controlled drug delivery (anticancer, antibiotic, and anti-inflammatory agents), wound healing, dental therapy, and bioactive implant coatings. Finally, we acknowledge that despite their broad potential, several associated challenges remain, including the synthesis scalability, batch-to-batch reproducibility, mechanical fragility of pure MBGs, and the complexity of predicting in vivo degradation and ion-release behaviors. We believe that emerging research directions, including eco-friendly synthesis routes, stimuli-responsive smart MBGs, multifunctional theranostic platforms, and patient-specific additive manufacturing, are poised to overcome current limitations and drive the next generation of MBG-based biomedical technologies. Full article

Recombinant human bone morphogenic protein-2 (rhBMP-2) use in spinal fusion is limited by dose-dependent complications. Peptide amphiphile (PA) supramolecular polymers presenting a BMP-2–binding epitope have previously been developed to reduce the rhBMP-2 dose required for successful fusion. We evaluated PA implant biodegradation and tissue clearance in a rat posterolateral spinal fusion model as a prerequisite to clinical safety studies. Twenty-three female Sprague–Dawley rats underwent L4–L5 fusion with gadolinium (Gd)-labeled PA implants. Longitudinal magnetic resonance imaging (MRI) was performed up to 13 weeks postoperatively, while the spine and filter organs were harvested for inductively coupled plasma mass spectrometry (ICP-MS) quantification of Gd at multiple time points. Gd concentration at the fusion site decreased from 71% of maximum to 19.5% at 13 weeks, and MRI showed a complete loss of Gd signal enhancement by 8 weeks. In peripheral organs, peak Gd accumulation was 3% in the liver at 4 weeks, declining to 1.4% at 13 weeks, while Gd remained below 0.05% in the spleen, lung, and blood at all time points. These data indicate PA implant localization, with robust degradation and clearance and minimal off-target accumulation, supporting its translational potential for spinal fusion applications. Full article

Bone regeneration in critical-size defects requires biomaterials that provide both structural support and appropriate osteoinductive cues. Natural nacre contains an organic matrix rich in acidic macromolecules with reported osteogenic activity; however, its in vivo regenerative potential remains insufficiently explored. This study evaluated the bone regenerative capacity of nacre-derived materials alone and combined with oxidized porous silicon microparticles (pSi-MP), a bioactive material known to release silicic acid and support mineralized tissue formation. Critical-size defects were created in four caudal vertebrae of Wistar rats and filled with nacre, pSi-MP, a nacre–pSi composite, or left empty. After 60 days, bone formation was assessed using micro-computed tomography and non-decalcified histology. Empty defects failed to regenerate, whereas nacre and pSi-MP individually promoted partial mineralized tissue deposition. The nacre–pSi composite produced the most extensive repair, showing near-complete defect bridging, higher bone mineral density, and seamless integration of particles within newly formed bone. No inflammation or adverse reactions were observed, and osteoid deposition occurred directly on material surfaces. These findings demonstrate that nacre-derived materials exert intrinsic osteogenic effects in vivo and that combining nacre with porous silicon yields a synergistic response that significantly enhances bone regeneration. The composite represents a promising candidate for future bone repair strategies. Full article

Background: Delayed or non-union fractures comprise 5–10% of cases, indicating the need for biologic interventions. Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a potent osteoinductive agent; yet, collagen carrier-based uncontrolled release causes adverse events. We evaluated the safety and efficacy of a hydroxyapatite (HA) carrier-based rhBMP-2 delivery system for acute traumatic upper and lower fractures exhibiting bone defects. Methods: This prospective, multicenter, single-arm clinical trial enrolled 90 patients who underwent surgery using a hydroxyapatite (HA) carrier-based rhBMP-2 delivery system (Novosis^TM). Radiographically validated union at 6 and 12 months post-surgery and treatment success (union without additional surgery) were used to assess efficacy. The incidence, type, and severity of all device-related adverse events during follow-up were monitored by investigators to evaluate safety. Results: Of the 90 patients enrolled, 81 were included in the full analysis set. The mean age was 58.5 years, and 18.6% (15/81) had open fractures. At 6 months post-surgery, radiographically validated union was achieved in 81.5% (66/81) of patients, increasing to 96.2% (77/81) at 12 months after surgery. Treatment success was 95.0% (76/81). Adverse events were rare (1/81, 1.2%). No ectopic ossification, systemic complications, or severe inflammatory responses were observed. Conclusions: HA-based rhBMP-2 intervention demonstrated favorable union rates and safety with minimal complications in acute upper and lower fractures with bone defects. The biocompatibility and controlled-release properties of HA likely improved efficacy and reduced complications. Results should be interpreted as feasibility data from a heterogeneous case series without a control group. Larger randomized controlled comparative trials are warranted for optimal dosing and evaluating efficacy and cost-effectiveness. Full article

This study investigates the effect of three-dimensional (3D) bioprinted collagen (Col) scaffolds (2% w/v collagen) loaded with autologous bone marrow stromal cells (BMSCs) and enriched with bone morphogenetic protein-2 (BMP-2) and hydroxyapatite-based particles (HAPPs) on bone regeneration in calvarial defects in rabbits. Three implant formulations, Col-(BMP-2) (at a concentration of 80 ng/mL), Col-HAPP (1% w/v) and a mixture of the two—Col-(BMP-2)-HAPP (40 ng/mL final concentration and 0.5% HAPP), were compared with a control group C-Per containing only periosteum to assess the influence of material structure, biochemical signals and cell component on osteogenesis. Histological analysis and quantitative computed tomography (CT) imaging parameters (HU values and residual defect diameter) showed significant differences between the groups, highlighting the role of combined strategies for optimal bone repair. The control group demonstrated the weakest regeneration, expressed by minimal lamellar bone and the largest residual defect. Col-(BMP-2) stimulated moderate osteoinduction with active osteoblasts but without a fully organised lamellar structure. Col-HAΡΡ provided more advanced regeneration, with histologically observed thick osteoid lamellae, early calcification, and structured lamellar architecture, emphasising the osteoconductive role of HAΡΡs. The strongest regeneration was reported with Col-(BMP-2)-HAΡΡ, where the synergy between BMP-2, HAΡΡs and BMSCs resulted in formed osteons, well-developed cancellous bone and minimal residual defects. The established negative correlation between bone density and residual calvarial defects emphasises the relationship between mineralisation and the degree of defect filling. The new data presented demonstrate that the combination of the abovementioned structural, biochemical and cellular factors in 3D bioprinted scaffolds offers a promising strategy for osteoregeneration of complex bone defects. Full article

In this study, the osteoinductive activity of a small-molecule NOTCH1 activator, Yhhu3792, and Poloxamer 407, an FDA-approved hydrogel, was evaluated independently regarding osteoblast functions in vitro using primary cultures of osteoblasts derived from C57BL/6J mice. We found that treatment with Yhhu3792 increased the number of NOTCH1-positive osteoblasts (36%) compared to the vehicle control (19%) after antibody staining, suggesting increased NOTCH1 signaling after Yhhu3792 treatment. Osteoblasts treated with varying doses (5, 10, and 20 μM) of Yhhu3792 and P407 (1–25%) stimulated both osteoblast proliferation and differentiation by 25–45% (p < 0.05) compared to the vehicle control. Accordingly, 10 µM Yhhu3792 treatment for 9 days increased the alizarin red-stained mineralized nodule area (8.69 ± 0.97 vs. 4.05 ± 1.51 arbitrary units; p < 0.05) compared to the vehicle treatment. Similarly, osteoblasts treated with 10% P407 also significantly increased mineralized nodule formation. The Cell Tox Green dye assay revealed that the dosage of Yhhu3792 used was not cytotoxic. Gene expression studies measured by real-time PCR revealed that a 24 h treatment with 10 µM Yhhu3792 significantly increased expression levels of bone formation markers (Vegf, Osteocalcin) and NOTCH1 targets (c-myc, Cox2, and Hes1) in osteoblasts. A low dose of P407 in combination with 10 µM Yhhu3792 stimulated a significant increase (>40%) in the proliferation of bone marrow stromal cells. In conclusion, our in vitro findings showing osteogenic effects of the small molecule Yhhu3792 and P407 hydrogel should be confirmed in vivo in animal fracture healing models. Full article

Bone tissue engineering offers a promising alternative to autografts and allografts for treating critical bone defects. Hydrogels, three-dimensional hydrophilic polymer networks, have emerged as leading scaffold materials due to their ability to mimic native extracellular matrix properties while providing tunable biocompatibility, biodegradability, mechanical characteristics, and high water content, enabling nutrient transport and cell viability. These scaffolds can be loaded with bioactive cues, including growth factors, peptides, and nanoparticles, and can deliver stem cells, supporting localised and sustained bone regeneration. Recent advances in hydrogel design have improved osteoinductivity and osteoconductivity through controlled physical, chemical, and mechanical properties, and sophisticated fabrication strategies such as 3D bioprinting and nanostructuring. This review provides a comprehensive overview of hydrogel-based scaffolds for bone tissue engineering, discussing material types, bioactive factor delivery, host tissue interactions, including immune modulation and osteogenic differentiation, and the latest preclinical and clinical applications. Finally, we highlight the remaining challenges and critical design requirements for developing next-generation hydrogels that integrate structural integrity with biological functionality. Full article

The design of biomaterial scaffolds for bone tissue engineering requires a balance between bioactivity, porosity, mechanical stability, and osteoinductivity. Kappa- (KC) and iota-carrageenan (IC) have been explored for scaffold fabrication due to their biocompatibility and structural similarity to glycosaminoglycans. However, there are limited reports on how their distinct sulfation degree affects the osteogenic differentiation of cells cultured on them. While laponite has been reported as an osteoinductive nanoclay, its combined effect with different carrageenan types and its concentration-dependent effect on scaffold functionality remain unexplored. Therefore, we developed composite scaffolds comprising poly(vinyl alcohol) (PVA) and gelatin (GEL), reinforced with kappa- or iota-carrageenan (KC, IC) and functionalized with two different concentrations of laponite (LAP), 0.5 and 1% w/v, to monitor composition-structure-function relationships. The scaffolds were fabricated via lyophilization and dual crosslinking, and characterized for their physicochemical, structural, mechanical, and biological properties. The incorporation of both carrageenans into scaffolds, maintained high swelling ratios of 600% after 24 h, and increased porosity without altering their apparent density (0.09–0.11 g/cm³), whereas LAP preserved interconnectivity, densified pore walls, raised their compressive modulus at >220 kPa, and improved stability (>60% mass retained after 40 days). In vitro validation using MC3T3-E1 pre-osteoblastic cells demonstrated robust cytocompatibility, with the LAP-containing scaffolds significantly promoting cell adhesion, proliferation, and osteogenic differentiation, evidenced by elevated alkaline phosphatase activity, calcium production and collagen secretion. Direct comparison between KC and IC scaffolds confirmed that differences in sulfate substitution modulated scaffold stiffness, swelling, and degradation, while variation in LAP concentration affected the biological response, with the 0.5 wt% concentration favoring early cell proliferation, whereas the 1 wt% significantly promoted the osteogenic differentiation. This compositional strategy demonstrates how tuning the interplay between carrageenan and laponite can balance scaffold hydration, mechanical and biological properties, thereby guiding the design of scaffolds for bone repair. Full article

In the context of guided bone regeneration (GBR), the selection of an appropriate resorbable membrane plays a crucial role in the clinical success of the procedure. Precise knowledge about the distinct differences in properties is fundamental for correct selection of the membrane. This article presents an integrated comparative analysis between membranes, conducted for this given purpose and one step beyond: to fabricate a novel membrane with dedicated enhanced properties according to the targeted function. Our previous analysis showed that polymer membranes that met most histopathological criteria also produced the most remarkable results when radiologically observed. The most effective scaffolds were those containing active macromolecules released conditionally and staged. The PLGA and polycaprolactone scaffolds were found in this category and they granted a marked increase in bone density and improvement in osteoinduction. Based on these results, we decided to create a new polycaprolactone membrane in order to compare it with a standard currently on the market, the Jason membrane. The Jason^® membrane is a natural collagen scaffold derived from porcine pericardium. Due to the unique production process, the membrane shows a natural honeycomb-like, multilayered collagen structure with an increased content of collagen type III, leading to remarkable tear resistance and a slow degradation rate. Also, the low thickness of 0.05–0.35 mm facilitates the soft tissue management. The Jason scaffold was compared to an innovative synthetic membrane based on polycaprolactone (PCL), focusing on their physicochemical characteristics, biological behavior, and clinical applicability. The Jason^® membrane was distinguished by its high biocompatibility and rapid integration, while PCL offered superior mechanical stability and long-term durability, making it a preferred option for complex or customized 3D regenerations. Based on this integrated analysis, we fabricated an innovative electrospun PCL membrane, enriched with a novel synthesized nanohydroxyapatite, in order to enhance its specific properties for the beneficial use in targeted reconstructions. Full article

Multiple myeloma (MM) is a plasma cell malignancy that disrupts bone homeostasis by suppressing osteogenesis and promoting osteoclast activity. While most therapeutic interventions to date have focused on targeting tumor cells and reducing osteolysis, we investigate whether osteoinductive strategies can restore bone formation and counteract disease progression. Using a human bone marrow-like scaffold model that enables direct in vivo evaluation of tumor–stroma interactions and human bone formation, we demonstrate that MM-derived mesenchymal stromal cells (MSCs) retain osteogenic potential but are functionally suppressed by MM cells. Transcriptomic profiling of MM-primed MSCs revealed the downregulation of small leucine-rich proteoglycans (SLRPs), ASPN, OGN, and OMD, key mediators of bone morphogenetic protein (BMP) signaling, which governs osteoblast differentiation. Among the BMPs analyzed, BMP6 emerged as a potent inducer of osteogenesis and regulator of the expression of these SLRPs. Notably, BMP6 selectively promoted bone formation without enhancing osteoclastogenesis and attenuated inflammatory and tumor-supportive MSC phenotypes. BMP6 also directly inhibited MM cell proliferation and suppressed IL6-induced growth. These findings highlight BMP6 as a distinct multifunctional regulator warranting further investigation as a potential therapeutic approach, while establishing the humanized model as a valuable platform for dissecting tumor–bone interactions in MM. Full article

Chitosan, a naturally derived polysaccharide obtained by chitin deacetylation, has attracted considerable attention in dentistry as a multifunctional biomaterial owing to its excellent biocompatibility, biodegradability, and tunable physicochemical properties. This narrative review provides an up-to-date overview of the use of chitosan-based sponges in dental tissue engineering, bone regeneration, post-extraction wound management, and periodontal therapy. Chitosan sponges, characterized by high porosity, flexibility, and superior absorbency, serve as effective wound dressings, drug delivery carriers, and scaffolds that promote cell proliferation and tissue regeneration. Their intrinsic antibacterial, antifungal, hemostatic, and immunomodulatory properties further enhance their therapeutic value in managing complex oral conditions. In periodontal treatment, they enable localized drug delivery and support soft and hard tissue healing, while in post-extraction care, they aid hemostasis and reduce complications such as alveolar osteitis. Moreover, their osteoconductive and osteoinductive potential positions them as promising materials for alveolar bone repair and implantology. Chemical modification of chitosan and the incorporation of bioactive compounds allow customization of sponge formulations to meet specific clinical needs. Despite encouraging preclinical findings, challenges remain due to variability in chitosan sources, differences in the degree of deacetylation, and limited clinical validation. This review highlights the potential of chitosan sponges as innovative tools in regenerative dentistry and underscores the need for further standardization, mechanistic studies, and long-term clinical trials to ensure their safe and effective translation into dental practice. Moreover, the broad clinical applications of chitosan sponges beyond dentistry confirm their potential as a universal biomaterial platform in regenerative medicine. Full article

Ferroptosis, a form of regulated cell death triggered by lipid peroxidation, is implicated in various degenerative diseases and bone regeneration. In this study, we hypothesized that the ferroptosis inhibitors Liproxstatin-1 (Lip-1) and Coenzyme Q10 (CoQ10) play a dual role in protecting cells against ferroptotic damage and promoting osteogenic differentiation in MC3T3-E1 cells. Erastin-induced ferroptosis significantly reduced cell viability and increased lipid peroxidation, as evidenced by BODIPY™ 581/591 C11 staining. Both Lip-1 and CoQ10 decreased lipid peroxidation and restored cell viability, particularly at early treatment points. Post-treatment recovery experiments showed that both agents reversed erastin-induced damage, with Lip-1 having a stronger and more sustained effect. ALP activity assays on day 14 revealed dose-dependent increases with Lip-1 and moderate stimulation with CoQ10, indicating additional osteoinductive properties. Moreover, cell density affected sensitivity to lipid peroxidation, with higher cell densities providing protection through antioxidant pooling. These results highlight CoQ10 and Lip-1 as promising candidates for bone tissue engineering, as they offer protection against ferroptosis and promote osteoblast differentiation. Overall, this study emphasizes the therapeutic potential of ferroptosis modulators for bone regeneration. Full article

Bone Morphogenetic Protein-2 (BMP2) is a growth factor that maintains bone homeostasis through the BMP receptor type Ia (BMPRIa) and type II (BMPRII). BMP2 promotes osteogenesis by inducing the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts; however, it can also trigger BMSC differentiation into adipocytes. BMP2’s osteo-inductive ability has made it a potential treatment for osteoporosis, yet its dual role in BMSC differentiation complicates its efficacy. High BMP2 levels cause BMPRIa cleavage, but the downstream effects and the mechanisms governing BMP2-induced osteogenesis or adipogenesis are unresolved. Here, we identify Caspase-1 as a key mediator of BMPRIa cleavage and its downstream effects on adipogenesis. We used primary BMSCs from C57BL/6 mice, stimulated with varying BMP2 concentrations, to explore BMP2-induced BMPRIa cleavage and its impact on PPARγ—a key regulator of adipogenesis. Western blotting and immunostaining using antibodies against BMPRIa and PPARγ uncovered BMPRIa cleavage and revealed the nuclear translocation of the cleaved segment, colocalizing with PPARγ. Caspase-1 inhibition significantly reduced BMPRIa cleavage and PPARγ expression, highlighting its pivotal role in adipogenic differentiation. Understanding the molecular mechanisms of BMP2-induced adipogenesis and Caspase-1 inhibition could improve BMP2 therapeutic efficacy for osteoporosis by promoting osteogenesis over adipogenesis. Full article

Objectives: Bone defects, resulting from many causes, represent a challenge in maxillofacial and orthopedic surgery. Regenerative medicine offers promising strategies by introducing exogenous materials to modify the tissue environment and modulate the body’s natural healing mechanisms. Dental pulp stem cells (DPSCs) are considered an effective source for tissue repair. Small molecules such as caffeic acid phenethyl ester (CAPE), although having promising effects in promoting bone regeneration, are characterized by low chemical stability, which impairs their clinical application. This study aimed to investigate the bone regenerative capability of four CAPE derivatives, recently synthesized in our laboratory and selected based on previous studies. Methods: DPSCs were induced to osteogenic differentiation in the presence of these compounds (0–5 μM), and cell viability, matrix deposition, alkaline phosphatase activity, and osteogenic marker gene expression were evaluated. In addition, bone biomaterials composed of a chitosan/agarose matrix reinforced with nanohydroxyapatite and enriched with these CAPE derivatives were fabricated and assessed for cytotoxicity and cell adhesion. Results: Two of the tested compounds effectively enhanced DPSC differentiation toward the osteogenic lineage. The fabricated bone biomaterials showed no cytotoxicity and supported cell adhesion. Furthermore, these compounds demonstrated stability under various conditions, confirming their suitability for incorporation into bone biomaterials. Conclusions: The tested CAPE derivatives exhibit promising osteoinductive properties and stability, offering a valid alternative to traditional therapeutic strategies in regenerative medicine. Full article