Search Results (482)

Background: Autologous tooth-derived grafts have recently gained attention as an innovative alternative to conventional biomaterials for alveolar ridge preservation (ARP) and augmentation (ARA). Their structural similarity to bone and osteoinductive potential support clinical use. Methods: This systematic review was conducted according to PRISMA 2020 guidelines and registered in PROSPERO (CRD420251108128). A comprehensive search was performed in PubMed, Scopus, and Web of Science (2010–2025). Randomized controlled trials (RCTs), split-mouth, and prospective clinical studies evaluating autologous dentin-derived grafts were included. Two reviewers independently extracted data and assessed risk of bias using Cochrane RoB 2.0 (for RCTs) and ROBINS-I (for non-randomized studies). Results: Nine studies involving 321 patients were included. Autologous dentin grafts effectively preserved ridge dimensions, with horizontal and vertical bone loss significantly reduced compared to controls. Histomorphometric analyses reported 42–56% new bone formation within 4–6 months, with minimal residual graft particles and favorable vascularization. Implant survival ranged from 96–100%, with stable marginal bone levels and no major complications. Conclusions: Autologous tooth-derived biomaterials represent a safe, biologically active, and cost-effective option for alveolar bone regeneration, showing comparable or superior results to xenografts and autologous bone. Further standardized, long-term RCTs are warranted to confirm their role in clinical practice. Full article

Background/Objectives: Human ovarian granulosa cells (hGCs) are crucial to ovarian follicle development and function, exhibiting multipotency and the ability to differentiate into neuronal cells, chondrocytes, and osteoblasts in vitro. 3,4,5,4′-tetramethoxystilbene (DMU-212) is a methylated derivative of resveratrol, a natural polyphenol found in grapes and berries, with a wide spectrum of biological activities, including notable anticancer properties. Interestingly, DMU-212 exhibits cytotoxic effects predominantly on cancer cells while sparing non-cancerous ones, and evidence suggests that similar to resveratrol, it may also promote hGC differentiation. This study aimed to investigate the effects of the liposomal formulation of this methylated resveratrol analog—lipDMU-212—on the osteogenic differentiation ability of hGCs in a primary three-dimensional cell culture model. Methods: lipDMU-212 was formulated using the thin-film hydration method. GC spheroids’ viability was evaluated after exposure to lipDMU-212, an osteoinductive medium, or both. Osteogenic differentiation was confirmed using Alizarin Red staining and quantified by measuring Alkaline Phosphatase (ALP) activity on days 1, 7, and 15. RNA sequencing (RNA-seq) was performed to explore molecular mechanisms underlying lipDMU-212-induced differentiation. Results: lipDMU-212 promoted osteogenic differentiation of hGCs in the 3D cell culture model, as evidenced by increased mineralization and a ~4-fold increase in ALP activity compared with the control. RNA-seq revealed up-regulation of genes related to cell differentiation and cellular identity. Furthermore, JUN (+2.82, p = 0.003), LRP1 (+2.06, p = 0.05), AXIN1 (+3.02, p = 0.03), and FYN (+3.30, p = 0.01) were up-regulated, indicating modulation of the Wnt/β-catenin signaling pathway, a key regulator of osteoblast differentiation. Conclusions: The ability of GCs to differentiate into diverse tissue-specific cell types underscores their potential in regenerative medicine. This study contributes to the understanding of lipDMU-212’s role in osteogenic differentiation and highlights its potential in developing future therapies for degenerative bone diseases. Full article

Heterotopic ossification (HO) is a disease characterized by ectopic bone formation, which can occur following severe traumatic brain injury (TBI). However, the underlying mechanisms remain poorly understood. In this study, we established a stem cell model using adipose-derived stem cells (ADSCs) and skeletal stem cells (SSCs) to examine osteogenic factors present in the sera of TBI patients. Incubation of ADSCs and SSCs with osteoinductive medium supplemented with TBI serum significantly enhanced osteogenic differentiation, particularly in male ADSCs and both female and male SSCs, with male SSCs exhibiting the highest osteogenic potential. Furthermore, we identified TGF-β1 as an important factor involved in these osteogenic processes. Elevated levels of TGF-β1 were detected in the serum of male TBI patients 14 days post-injury. Cellular assays revealed a sexual dimorphism in response to TGF-β1 neutralization: osteogenic differentiation in male SSCs was significantly reduced, while no effect was detectable in female SSCs. These findings, together with the rarity of HO in female patients, suggest that TGF-β1 plays a central role in the development of HO in males. Furthermore, this study highlights the importance of considering sex-specific mechanisms in traumatic HO for the development of sex-specific therapy options. Full article

Metallic nanoparticles (MNPs) have emerged as leading candidates in biomedical applications owing to their unique physicochemical properties and dual functionality, combining potent bactericidal and osteoinductive effects. These bioactivities are intricately governed by structural parameters such as size, shape, crystallinity, and chemical composition, which collectively dictate their interactions with biological systems. These interactions affect key mechanisms including oxidative stress induction, membrane disruption, and modulation of cellular signaling pathways. Despite considerable progress, a comprehensive understanding of the structure property–activity-specific structural relationship in MNPs remains incomplete, hindering the rational design of optimized nanomaterials. This review critically examines recent advances in elucidating the bactericidal and osteoinductive mechanisms of MNPs, with a particular focus on the role of structural determinants. Furthermore, current challenges and future directions for tailoring nanoparticle architecture to enhance clinical performance are discussed. To address this, we conducted a systematic review of the literature published between 2005 and 2024 using Web and Web of Science direct and Scopus databases. Our analysis is structured around a structure →mechanism→outcome perspective, linking nanoparticle features to biological responses. Key insights include the following: (i) nanoparticles below ~20 nm generally enhance bacterial efficiency through enhanced membrane disruption; (ii) surface hydroxyl density above critical thresholds promotes osteogenic signaling; and (iii) safe concentration windows remain narrow, highlighting the importance of dose optimization. We conclude by discussing the translational challenges and future directions for tailoring nanoparticle architectures to advance clinical applications. 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

Successful arthrodesis is a crucial factor in spinal fusion surgery, maximizing the likelihood of improved quality of life. The incorporation of metals into bone grafts has been demonstrated to enhance fusion rates through various osteoinductive and osteoconductive pathways. A systematic review was conducted to investigate the utility of metal composite bone grafts in promoting arthrodesis in spinal fusion preclinical studies. PubMed/MEDLINE was queried to identify studies investigating metal composite bone grafts in animal models of spinal fusion. Non-spinal fusion animal models were excluded. Risk of bias was assessed using the SYRCLE risk of bias tool. After screening a total of 1554 articles, 17 articles were included in our review. Metal composite bone grafts with bioactive agents had significantly greater fusion rates than metal composite only bone grafts (p < 0.001) and similar fusion rates compared to non-metal comparator bone grafts (p = 0.172). Bone grafts containing strontium and magnesium had the greatest fusion rates compared to other metals and had significantly greater fusion rates than those of silicon-containing bone grafts (p = 0.02 and p = 0.04, respectively). Bone quality and bone volume percentages of fusion masses formed by metal composite bone grafts were enhanced via the addition of bioactive agents such as stem cells, rhBMP-2, autograft, and poly (lactic-co-glycolic acid). The adverse event rate was 3.0% in all animal surgeries. Metal composite bone grafts show promise as osteoinductive agents to promote arthrodesis in spinal fusion, and their osteoinductive capability is enhanced with the synergistic addition of osteogenic factors such as stem cells and autograft. Full article

In regenerative medicine, orthobiologics, particularly platelet-rich plasma (PRP), are widely used due to their ability to enhance natural tissue repair mechanisms. PRP contains a concentrated pool of growth factors and cytokines that enhance regeneration while also acting as a biomimetic scaffold, thereby optimizing the microenvironment for tissue healing. In bone tissue engineering, PRP is commonly combined with synthetic or natural biomaterials, as its fibrin matrix alone lacks sufficient mechanical stability. However, even such composite systems frequently exhibit limited osteoinductive capacity, necessitating further supplementation with bioactive components. This review evaluates the regenerative potential of PRP in bone defect healing when combined with osteoinductive agents in preclinical in vivo models. We present compelling experimental evidence supporting the efficacy of this combined therapeutic approach. Full article

Sim, a potent HMG-CoA reductase inhibitor, exhibits notable anabolic effects on bone and can upregulate osteogenic genes such as BMP-2, thereby promoting bone formation. An ideal drug delivery system for Sim involves its controlled and sustained release at the defect site to minimize adverse side effects. In this study, Sim was first modified via HP-γ-CD to form a hydrophilic Sim/HP-γ-CD inclusion complex, thereby improving drug solubility and dispersion in aqueous systems. A gelatin–sodium alginate (Gel/SA) hydrogel was then employed as the drug delivery matrix to construct a Gel-SA-Sim/HP-γ-CD hydrogel sustained release system. This hydrogel system exhibited a high water content (82%), along with enhanced mechanical properties, including a compressive strength of 0.284 MPa and a compressive modulus of 0.277 MPa, suggesting strong load-bearing capacity and favorable stiffness. Importantly, Sim was released in a controlled and sustained manner over 7 days, without exhibiting burst release behavior. In vitro osteogenic differentiation assays demonstrated that optimal concentrations of Sim effectively enhanced cellular bioactivity and osteoinductive performance, offering a promising approach to enhance the bioactivity, osteogenesis, and osseointegration of orthopedic implants. Full article

This review article provides a comprehensive evaluation of Infuse^® and InductOs^®, two ground-breaking recombinant human Bone Morphogenetic Protein-2 (rhBMP-2)-based bone graft products, focusing on their tissue-level regenerative responses, clinical applications, and associated costs. Preclinical and clinical studies demonstrate that rhBMP-2 induces strong osteoinductive activity, effectively promoting mesenchymal stem cell differentiation and vascularized bone remodeling. While generally well-tolerated, these osteoinductive effects are dose-dependent, and excessive dosing or off-label use may result in adverse outcomes, such as ectopic bone formation or soft tissue inflammation. Histological and imaging analyses in craniofacial, orthopedic, and spinal fusion models confirm significant bone regeneration, positioning rhBMP-2 as a viable alternative to autologous grafts. Notably, advances in delivery systems and scaffold design have enhanced the stability, bioavailability, and targeted release of rhBMP-2, leading to improved fusion rates and reduced healing times in selected patient populations. These innovations, alongside its proven regenerative efficacy, underscore its potential to expand treatment options in cases where autografts are limited or unsuitable. However, the high initial cost, primarily driven by rhBMP-2, remains a critical limitation. Although some studies suggest overall treatment costs might be comparable to autografts when factoring in reduced complications and operative time, autografts often remain more cost-effective. Infuse^® has not substantially reduced the cost of bone regeneration and presents additional safety concerns due to the rapid (burst) release of growth factors and limited mechanical scaffold support. Despite representing a significant advancement in synthetic bone grafting, further innovation is essential to overcome limitations related to cost, mechanical properties, and controlled growth factor delivery. Full article

Background/Objectives: Hydrogels have emerged as strategic biomaterials in bone tissue engineering, especially in the peri-implant context, due to their high biocompatibility, water retention capacity, three-dimensional defect filling, and ability to mimic the extracellular matrix. These properties allow physical support for regeneration and the incorporation and controlled release of bioactive, immunomodulatory, and osteoinductive agents. Methods: This narrative review aimed to summarize recent advances in developing and applying hydrogels for the repair of peri-implant bone defects. The selection of studies was performed in PubMed, Web of Science, and EBSCO databases, covering the period from 2010 to 2025. Thus, 14 preclinical and clinical studies were included in this review. Results and Conclusions: Hydrogels show great potential for peri-implant bone regeneration due to their biocompatibility and ability to deliver bioactive agents. While preclinical results are promising, clinical validation remains limited. Further studies are needed to confirm their efficacy and ensure the safe translation of these findings into clinical practice. Full article

Background: A trilayered collagen/collagen–magnesium–hydroxyapatite (Col/Col-Mg-HA) scaffold is used in clinical practice to treat osteochondral lesions, but the regeneration of the subchondral bone is still not satisfactory. Objective: The aim of this study was to test, in vitro, the osteoinductivity induced by the addition of bone morphogenetic protein-2 (BMP-2) or amorphous calcium phosphate granules with strontium ions (Sr-ACP), in order to improve the clinical regeneration of subchondral bone, still incomplete. Methodology: Normal human osteoblasts (NHOsts) were seeded on the scaffolds and grown for 14 days in the presence of human osteoclasts and conditioned medium of human endothelial cells. NHOst adhesion and morphology were observed with transmission electron microscopy, and metabolic activity was tested by Alamar blue assay. The expression of osteoblast- and osteoclast-typical markers was evaluated by RT-PCR on scaffolds modified by enrichment with BPM-2 or Sr-ACP, as well as on unmodified material used as a control. Results: NHOsts adhered well to all types of scaffolds, maintained their typical morphology, and secreted abundant extracellular matrix. On the modified materials, COL1A1, SPARC, SPP1, and BGLAP were more expressed than on the unmodified ones, showing the highest expression in the presence of BMP-2. On Sr-ACP-enriched scaffolds, NHOsts had a lower proliferation rate and a lower expression of RUNX2, SP7, and ALPL compared to the other materials. The modified scaffolds, particularly the one containing Sr-ACP, increased the expression of the osteoclasts’ typical markers and decreased the OPG/RANKL ratio. Both types of scaffold modification were able to increase the osteoinductivity with respect to the original scaffold used in clinical practice. BMP-2 modification seemed to be more slightly oriented to sustain NHOst activity, and Sr-ACP seemed to be more slightly oriented to sustain the osteoclast activity. These could provide a concerted action toward better regeneration of the entire osteochondral unit. Full article

Osteoporosis compromises bone quality and impairs implant osseointegration. Since an adequate bone bed is essential for implant stability and success, this study evaluated the effects of implant surface functionalization with zoledronic acid (ZOL), alone or combined with ruterpy (TERPY), on peri-implant bone healing in healthy (SHAM) and osteoporotic (OVX) rats. ZOL has antiresorptive properties, while TERPY exhibits osteoinductive potential. The hypothesis was that ZOL + TERPY would act synergistically by inhibiting bone resorption and promoting new bone formation. Sixty-six female Wistar rats (3 months old) were divided into six groups (n = 11) according to systemic condition (SHAM or OVX) and implant type: conventional (CONV), ZOL, or ZOL + TERPY. Surgeries (sham or bilateral ovariectomy) were performed on day 0, and implants were placed in the tibial metaphysis on day 90. Fluorochromes were administered on days 104 (calcein) and 114 (alizarin), and euthanasia was performed on day 118. Samples were analyzed histologically via confocal microscopy and micro-computed tomography (Micro-CT). The ZOL + TERPY groups demonstrated significantly accelerated peri-implant bone repair, showing greater bone formation and organization; improved BV/TV, Tb.N, and I.S.; and reduced Tb.Sp and Po.Tot compared to CONV and ZOL-alone groups. In conclusion, ZOL + TERPY enhances and speeds bone healing, even under osteoporotic conditions. Full article

In this study, a shape-changeable 3D scaffold with photothermal effects was developed to address the clinical challenges of complex bone defects. The multifunctional construct was fabricated via in situ polymerization combined with a gas foaming technique, creating hierarchical porous architectures that mimic the native bone extracellular matrix. By incorporating polydopamine (PDA)-modified amorphous calcium phosphate (CA) into poly(propylene glycol) (PPG)- and poly(ԑ-caprolactone) (PCL)-based polyurethane (PU). The obtained scaffolds achieved osteoinductive potential for bone tissue engineering. The surface PDA modification of CA enabled efficient photothermal shape conversion under near-infrared (NIR) irradiation, facilitating non-invasive remote control of localized hyperthermia. The optimized scaffolds exhibited interconnected porosity (approximately 70%) with osteoconductive pore channels (200–500 μm), resulting in good osteoinduction in cell culture, and precise shape-memory recovery at physiological temperatures (~40 °C) under NIR for minimally invasive delivery. The synergistic effect of osteogenesis promotion and photothermal transition demonstrated this programmable scaffold as a promising solution for integrated minimally invasive bone repair and defect reconstruction. Full article

Staphylococcus species are often the cause of implant-related infections, posing a significant clinical challenge in orthopedics. Antimicrobial peptides (AMPs) like LL-37-derived FK-16 and GF-17 offer promising alternatives to conventional antibiotics; however, they require suitable delivery systems to overcome rapid degradation. The aim of this study was to develop and evaluate silk fibroin (SF) and osteoinductive peptide-enriched silk fibroin (PSF) sponges that can be used locally for FK-16 and GF-17 delivery. Two concentrations of FK-16 or GF-17 were loaded into SF and PSF sponges. Swelling behavior and AMP release profiles were analyzed for 72 h. Time-kill assays were conducted on MRSE and MRSA clinical strains to assess antimicrobial activity. FK-16 released quickly (>90% within 24 h) and then maintained a stable plateau from both SF and PSF matrices, which was associated with bactericidal activity against MRSE strains. In contrast, the release efficiency of GF-17 was lower and did not achieve significant antimicrobial effects. Neither peptide exhibited effective activity against MRSA under the tested conditions. PSF sponges showed higher swelling and enhanced FK-16-mediated antibacterial performance compared to SF counterparts. FK-16-loaded PSF sponges are a promising biomaterial for treating local orthopedic infections related to MRSE. The findings underscore the significance of peptide–matrix interactions in determining therapeutic outcomes and suggest the need for more in vivo evaluation of AMP-functionalized PSF scaffolds. Full article