Search Results (89)

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

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

Patient-specific cutting guides are used for safe and accurate jaw resection during oral and maxillofacial surgery. This study investigated the effect of shavings from 3D-printed cutting guide materials during surgery on bone healing. The biocompatibility of commercially available biocompatible polymers including photopolymer resin (PP) and polyamide resin (PA) materials was assessed in the present study. The viability of mouse osteoblast-like MC3T3E-1 cells was evaluated upon coculture with the materials. Furthermore, the effects of PP and PA as additives on bone formation were investigated in a rat calvarial bone defect model. Both PP and PA were biocompatible and allowed cells to attach to them. However, both materials could be damaged when cutting devices were used, and their shavings impaired osteoblast proliferation and bone formation. Cutting guide materials are designed to be biocompatible when they are fabricated according to the manufacturer’s protocol. Nevertheless, the polymer shavings generated during jaw cutting might adversely affect bone healing. Full article

Background: Three-dimensional (3D) printed scaffolds have emerged as promising tools for bone regeneration, but the optimal structural design and pore size remain unclear. Polylactic acid (PLA) reinforced with graphene oxide (GO) offers enhanced mechanical and biological performance, yet systematic evaluation of architecture and pore size is limited. Methods: Two scaffold architectures (lattice-type and dode-type) with multiple pore sizes were fabricated using UV-curable PLA/GO resin. Physical accuracy, porosity, and mechanical properties were assessed through compression and fatigue testing. Based on in vitro screening, four pore sizes (930 μm, 690 μm, 558 μm, 562 μm) within the dode-type structure were analyzed. The 558 μm and 562 μm scaffolds, showing distinct fracture thresholds, were further evaluated in rat and rabbit calvarial defect models for inflammation and bone regeneration. Results: In vitro testing revealed that while 930 μm and 690 μm scaffolds exhibited superior compressive strength, the 562 μm scaffold showed a unique critical fracture behavior, and the 558 μm scaffold offered comparable stability with higher resistance to premature failure. In vivo studies confirmed excellent biocompatibility in both groups, with early bone formation favored in the 558 μm scaffold and more continuous and mature bone observed in the 562 μm scaffold at later stages. Conclusions: This stepwise strategy—from structural design to pore size screening and preclinical validation—demonstrates that threshold-level mechanical properties can influence osteogenesis. PLA/GO scaffolds optimized at 558 μm and 562 μm provide a translationally relevant balance between mechanical stability and biological performance for bone tissue engineering. Full article

Calvarial suture skeletal stem cells (Su-SSCs) are a distinct stem cell population for craniofacial bone formation by intramembranous ossification, compared to long bone periosteal SSCs (LB-PSSCs) with endochondral (osteochondrogenic) ossification. However, whether SSC intrinsic or extrinsic factors affect their differentiation process has not been well elucidated. Here, using an inducible Prx1-CreER-EGFP^+/−;Rosa26-tdTomato mouse model, we observed that endogenous Prx1⁺ Su-SSCs and their orthotopic transplantation into calvarial injury do not form cartilage intermediates at the injury sites, while the transplantation of Prx1⁺ LB-PSSCs into LB injury induces osteochondrogenic differentiation, respectively. However, the heterotopic transplantation of Prx1⁺ Su-SSCs (Su-SSCs into LB injury) showed some surprising findings that the transplanted Su-SSCs acquire new chondrocyte differentiation properties at the LB injury sites, although the heterotopic-transplanted Prx1⁺ LB-PSSCs maintained their endochondral ossification properties at the calvarial injury sites. Further, a comparative single-cell transcriptomic analysis of LB-PSSCs and Su-SSCs revealed that Su-SSCs express a higher set of anti-chondrogenic genes, such as Wnt5b, Twist1 while LB-PSSCs highly express chondrogenic Hoxa-9, Hoxc-9, Hoxa-10, Hoxc-10, and Comp genes. We also found that the heterotopic transplantation of LB-PSSCs into calvarial injury enhances bone healing in vivo. Taken together, these findings suggest that LB-PSSCs have high regenerative capability with invariable endochondral ossification even after the heterotopic transplantation but Su-SSCs are more flexible and regulated by the local bone environment. The transplantation of periosteal SSCs will be a promising method for large craniofacial bone defects. Full article

In the present study, we evaluated the usefulness of a porous sintered calcium carbonate body with CaSiO₃ by comparing its osteogenic capacity with that of calcium carbonate without CaSiO₃ and that of β-tricalcium phosphate (TP). A cranial defect model of eight-week-old male Wistar rats was divided into three groups: calcium carbonate (CC), calcium carbonate-CaSiO₃ composite (CC+CS), and TP. Micro-computed tomography (CT) and histological analysis were performed at four and eight weeks postoperatively. Upon quantitative evaluation of newly formed bone volume by radiography, the CC+CS group demonstrated the highest value at eight weeks postoperatively and exhibited significantly more new bone formations than the CC group (p < 0.05). Upon histological evaluation, the CC+CS group demonstrated significantly higher new bone formation than the CC group (p < 0.05). Furthermore, in terms of residual graft material ratio, at eight weeks postoperatively, the amount of residual graft material in the CC+CS group was significantly higher than that in the TP group (p < 0.05). Therefore, the addition of CaSiO₃ enhances the functional regulation of calcium carbonate-based artificial bone and can be incorporated in bone graft materials. Full article

This study sought to evaluate the inhibitory effect of pulsed electromagnetic field (PEMF) therapy on bone resorption in a mouse model of lipopolysaccharide (LPS)-induced osteoporosis. A total of 40 mice were divided into four groups: control, LPS, LPS + alendronate, and LPS + PEMF. Blood and spleen samples were analyzed using RT-PCR and ELISA, while calvaria and femurs were assessed by micro-computed tomography (CT) and histological analysis. Serum analysis revealed that, compared with the control group, calcium levels in the PEMF group showed no significant difference, but alkaline phosphatase (ALP) levels were significantly increased, whereas tartrate-resistant acid phosphatase (TRAP) levels were significantly decreased. Moreover, blood cytokine analysis showed reduced expression of TNF-α and IL-1β and increased expression of BMP-2 in the PEMF group. Spleen tissue analysis further demonstrated significant upregulation of IFN-γ and IL-10 expression in the PEMF group. Micro-CT confirmed that PEMF inhibited femoral bone loss and promoted bone regeneration in calvarial defects. Histological evaluation with hematoxylin and eosin and Masson–Goldner trichrome staining confirmed enhanced bone formation in both the femur and calvaria. In conclusion, PEMF effectively alleviates bone loss and promotes bone regeneration in LPS-induced osteoporosis. Furthermore, PEMF exhibits anti-osteoclastogenic activity by reducing inflammatory cytokines and enhancing IFN-γ and IL-10 expression in the spleen. Full article

This systematic review aimed to evaluate the effectiveness of teriparatide (TP) in guided bone regeneration (GBR). An electronic search without language or date restrictions was performed in PubMed, Web of Science, Scopus, Scielo, and gray literature for articles published until June 2025. Inclusion criteria considered studies evaluating the effect of TP on bone regeneration, analyzed using SYRCLE’s Risk of Bias tool. Twenty-four preclinical studies were included, covering diverse craniofacial models (mandibular, calvarial, extraction sockets, sinus augmentation, distraction osteogenesis, segmental defects) and employing systemic or local TP administration. Teriparatide consistently enhanced osteogenesis, graft integration, angiogenesis, and mineralization, with potentiated effects when combined with various biomaterials, including polyethylene glycol (PEG), hydroxyapatite/tricalcium phosphate (HA/TCP), biphasic calcium phosphate (BCP), octacalcium phosphate collagen (OCP/Col), enamel matrix derivatives (EMDs), autografts, allografts, xenografts (Bio-Oss), strontium ranelate, and bioactive glass. Critically, most studies presented a moderate-to-high risk of bias, with insufficient randomization, allocation concealment, and blinding, which limited the internal validity of the findings. TP shows promising osteoanabolic potential in guided bone regeneration, enhancing bone formation, angiogenesis, and scaffold integration across preclinical models. Nonetheless, its translation to clinical practice requires well-designed human randomized controlled trials to define optimal dosing strategies, long-term safety, and its role in oral and craniomaxillofacial surgical applications. Full article

Purpose: Collagen membranes with biomimetic mineralization are emerging as promising materials for bone regeneration, owing to their high biocompatibility. In this study, we developed a biogenic collagen membrane by combining citrate (C) pretreatment and carboxymethyl chitosan (CMC)-mediated mineralization and further evaluated its bone healing potential. Methods: C-CMC collagen membranes were prepared by lyophilization. The mineral composition and content were tested through X-ray diffraction (XRD), Fourier transform infrared (FTIR), and thermogravimetric analysis (TGA). The micromorphology was observed using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and scanning probe microscopy (SPM). Physical and mechanical properties, including the swelling rate, porosity, hydrophilicity, tensile strength, Young’s modulus, degradation, and barrier function, were also evaluated. Bone mesenchymal stem cells (BMSCs) were cultured in vitro to observe their behavior. An in vivo critical-size rat calvarial defect model was used to validate the effects of the membrane on bone regeneration. Results: The C-CMC collagen membrane was successfully synthesized as a collagen–hydroxyapatite complex with intrafibrillar mineralization, exhibiting improved mechanical properties and an optimal swelling rate, porosity, hydrophilicity, and degradation rate. Additionally, the C-CMC collagen membrane promoted BMSC proliferation, adhesion, and osteogenesis while preventing epithelial cell infiltration. In vivo experiments indicated that C-CMC collagen membranes significantly stimulated bone regeneration without causing systemic toxicity. Conclusions: Our findings suggest that the C-CMC collagen membrane possesses satisfactory physical and mechanical properties, along with good biocompatibility and efficacy in bone defect regeneration, making it a potential candidate for a bioactive guided bone regeneration membrane in clinical applications. Full article

Alveolar bone loss due to trauma, extraction, or periodontal disease often requires bone grafting prior to implant placement. Although human allograft bone is widely used as an alternative to autograft, it has limited osteoinductive potential and a prolonged healing time. Mesenchymal stem cell–conditioned media (MSC-CM), rich in paracrine factors, has emerged as a promising adjunct to enhance bone regeneration. This study evaluated the regenerative effect of MSC-CM combined with human allograft bone in a rabbit calvarial defect model. Bilateral 8 mm defects were created in eight rabbits. Each animal received a human allograft alone (HB group) on one side and an allograft mixed with MSC-CM (HB+GF group) on the other. Histological and histomorphometric analyses were performed at 2 and 8 weeks postoperatively. Both groups showed new bone formation, but the HB+GF group demonstrated significantly greater bone regeneration at both time points (p < 0.05). New bone extended into the defect center in the HB+GF group. Additionally, greater graft resorption and marrow formation were observed in this group at 8 weeks. These findings suggest that MSC-CM enhances the osteogenic performance of human allograft bone and may serve as a biologically active adjunct for bone regeneration. Full article

Aim: to evaluate the bone regeneration capacity of two alloplastic biomaterials in a critical-size rat calvarial defect model. Methods: A total of 80 rats were randomized into 8 groups of 10 animals each. An Ø8 mm, critical-size calvarial defect was created, and the following treatments were randomly allocated: sham surgery, deproteinized bovine bone mineral (DBBM) + collagen membrane (CM), poly-(lactic-co-glycolic-acid) (PLGA)-coated pure phase β-tricalcium phosphate (β-TCP), or PLGA-coated 60% hydroxyapatite (HA):40%β-TCP. Animals were allowed to heal for 2 and 6 weeks. Microcomputed tomography (μCT) was used to evaluate mineralized tissue and biomaterial displacement. Histological samples were used to evaluate new bone formation. Results: μCT analysis showed no significant differences among groups for total volume of mineralized tissue or residual biomaterials. DBBM + CM showed significantly increased horizontal biomaterial displacement at 2 weeks but not at 6 weeks. Histological analysis showed that sham surgery had a significantly higher percentage of bone area fraction than the DBBM + CM and PLGA + β-TCP at 2 weeks, but not at 6 weeks. Residual biomaterial area fraction showed no significant differences among experimental groups at any healing time. Conclusions: The alloplastic biomaterials showed suitable construct integrity and retention in the defect. All biomaterials were associated with limited new bone formation comparable to the sham surgery control. Full article

This study developed electrosprayed deferoxamine (DFO)-loaded poly(lactic-co-glycolic acid) microspheres (DFO-MS) combined with a sucrose acetate isobutyrate (SAIB) depot (DFO-MS@SAIB) for bone-defect repair, targeting the coordinated regulation of angiogenesis and osteogenesis in vascularized bone regeneration—where new blood vessels support functional bone integration. In vitro/in vivo evaluations confirmed its dual pro-angiogenic and pro-osteogenic effects via HIF-1α pathway activation. Background/Objectives: Emerging evidence underscores the indispensability of vascularization in bone-defect repair, a clinical challenge exacerbated by limited intrinsic healing capacity. While autologous grafts and growth-factor-based strategies remain mainstream, their utility is constrained by donor-site morbidity, transient bioactivity, and poor spatiotemporal control over angiogenic–osteogenic coupling. Here, we leveraged DFO, a hypoxia-mimetic HIF-1α stabilizer with angiogenic potential, to engineer an injectable DFO-MS@SAIB depot. This system was designed to achieve sustained DFO release, thereby synchronizing vascular network formation with mineralized tissue regeneration in critical-sized defects. Methods: DFO-MS were fabricated via electrospraying and combined with SAIB (DFO-MS@S) to form an injectable sustained-release depot. Their physicochemical properties, including morphology, encapsulation efficiency, degradation, release kinetics, and rheology, were systematically characterized. In vitro, the angiogenic capacity of HUVECs co-cultured with DFO-MS was evaluated; conditioned HUVECs were then co-cultured with BMSCs to assess the BMSCs’ cytocompatibility and osteogenic differentiation. In vivo bone regeneration in a rat calvarial defect model was evaluated using micro-CT, histology, and immunohistochemistry. Results: The DFO-MS@SAIB system achieved sustained DFO release, stimulating HUVEC proliferation, migration, and tubulogenesis. In a Transwell co-culture model, pretreated HUVECs promoted BMSC migration and osteogenic differentiation via paracrine signaling involving endothelial-secreted factors (e.g., VEGF). HIF-1α pathway activation upregulated osteogenic markers (ALP, Col1a1, OCN), while in vivo experiments demonstrated enhanced vascularized bone regeneration, with significantly increased bone volume/total volume (BV/TV) and new bone area compared with controls. Conclusion: The DFO-MS@SAIB system promotes bone regeneration via sustained deferoxamine release and HIF-1α-mediated signaling. Its angiogenesis–osteogenesis coupling effect facilitates vascularized bone regeneration, thereby offering a translatable strategy for critical-sized bone-defect repair. Full article

Background/Objectives: Bone regeneration using nanomaterial-based approaches shows promise for treating critical bone defects. However, developing sustainable and cost-effective therapeutic materials remains challenging. This study investigates the osteogenic potential of clove-derived carbon dots (C-CDs) for bone regeneration applications. Methods: C-CDs were synthesized using a green hydrothermal method. The osteogenic potential was evaluated in human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and validated using ectopic bone formation and calvarial defect models. Results: C-CDs demonstrated uniform morphology (~10 nm) with efficient cellular uptake. In vitro studies showed successful osteogenic differentiation through the upregulation of RUNX2, ALP, COL1A1, and BMP-2 mediated by Wnt/β-catenin/GSK3β and BMP signaling pathways. In vivo models have also demonstrated that C-CDs are effective in promoting bone regeneration. Conclusions: These findings establish C-CDs as promising candidates for bone regeneration therapy, offering a sustainable alternative to current treatments. While optimization is needed, their demonstrated osteogenic properties warrant further development for regenerative medicine applications. Full article

Background/Objectives: Delays in bone healing and complications of remodeling constitute a major medical problem—particularly in older adults and patients with comorbidities. Current therapeutic approaches are based on strategies that promote bone regeneration. We recently identified a disaccharide compound (DP2) that enhances in vitro mineralization in human osteoblast cells via the early activation of Runx2 and the induction of osteoblast differentiation. Methods: First, a calcium quantification assay was performed to assess mineralization in MC3T3-E1 cells. Next, microcomputed tomography and histological analyses were used to examine in vivo bone repair in a rat 5 mm cranial defect model following the implantation of DP2 coupled to a micro/macroporous biphasic CaP ceramic (MBCP⁺) or collagen scaffold. Results: Here, we demonstrated that DP2 induced osteogenic differentiation and significantly elevated calcium matrix deposition in the murine preosteoblast cell line MC3T3-E1. We found that treatment with DP2 coupled to MBCP⁺ repaired the calvarial defect on post-implantation day 91. It significantly increased bone mineral density starting on day 29 post-treatment. In addition, DP2 did not induce ectopic bone formation. Conclusions: Taken as a whole, these results show that DP2 is a promising candidate treatment for delayed bone healing. Full article

Under benign conditions, bone tissue can regenerate itself without external intervention. However, this regenerative capacity can be compromised by various factors, most importantly related with the extent of the injury. Critical-sized defects, exceeding the body’s natural healing ability, demand the use of temporary or permanent devices like artificial joints or bone substitutes. While titanium is a widely used material for bone replacement, its integration into the body remains limited. This often leads to the progressive loosening of the implant and the need for revision surgeries, which are technically challenging, are commonly associated with high complication rates, and impose a significant economic burden. To enhance implant osseointegration, numerous studies have focused on the development of surface functionalization techniques to improve the response of the body to the implant. Yet, the challenge of achieving reliable and long-lasting prostheses persists. In this work, we address this challenge by applying a robust and versatile biofunctionalization process followed by the decoration of the material with oligopeptides. We immobilize four different peptides (RGD, CS-1, IKVAV, PHSRN) on R-THAB^® functionalized surfaces and find them to be highly stable in the long term. We also find that RGD is the best-performing peptide in in vitro cell cultures, enhancing adhesion, proliferation, and osteogenic differentiation of mesenchymal stem cells. To assess the in vivo effect of RGD-decorated Ti-6Al-4V implants, we develop a calvarial model in murine hosts. We find that the RGD-decoration remains stable for 1 week after the surgical procedure and reduces post-implantation macrophage-related inflammation. These results highlight the potential of peptide decoration on R-THAB^® functionalized surfaces to expedite the development of novel metallic biomaterials with enhanced biocompatibility properties, thereby advancing the field of regenerative medicine. Full article