Search Results (116)

Effective bone tissue regeneration remains pivotal in implant dentistry, particularly for edentulous patients with compromised alveolar bone due to atrophy and sinus pneumatization. Biomaterials are essential for promoting regenerative processes by supporting cellular recruitment, vascularization, and osteogenesis. This study presents the development and characterization of a novel lithography-printed ceramic β-TCP scaffold, with a macro/micro-porous lattice, engineered to optimize osteoconduction and mechanical stability. Morphological, structural, and biomechanical assessments confirmed a reproducible microarchitecture with suitable porosity and load-bearing capacity. The scaffold was also employed for maxillary sinus augmentation, with postoperative evaluation using micro computed tomography, synchrotron imaging, histology, and Fourier Transform Infrared Imaging analysis, demonstrating active bone regeneration, scaffold resorption, and formation of mineralized tissue. Advanced imaging supported by deep learning tools revealed a well-organized osteocyte network and high-quality bone, underscoring the scaffold’s biocompatibility and osteoconductive efficacy. These findings support the application of these 3D-printed β-TCP scaffolds in regenerative dental medicine, facilitating tissue regeneration in complex jawbone deficiencies. Full article

Large segmental bone defects present significant challenges due to the insufficient vascularization of implanted grafts, necessitating advances in vascularized bone tissue engineering. Recent innovations focus primarily on enhancing graft vascularization through advanced biomaterial scaffolds, precise three-dimensional (3D) bioprinting technologies, biochemical interventions, and co-culture techniques. Biomaterial scaffolds featuring microchannels and high-surface-area architectures facilitate endothelial cell infiltration and subsequent vessel formation. Concurrently, sophisticated 3D-bioprinting methods, including inkjet, extrusion, and laser-assisted approaches, enable the precise placement of endothelial and osteogenic cells, promoting anatomically accurate vascular networks. Biochemical strategies that utilize the simultaneous delivery of angiogenic factors (e.g., vascular endothelial growth factor) and osteogenic factors (e.g., bone morphogenetic protein-2) effectively couple angiogenesis and osteogenesis. Additionally, co-culturing mesenchymal stem cells and endothelial progenitors accelerates the development of functional capillary networks. Preclinical studies consistently demonstrate superior outcomes for prevascularized grafts, as evidenced by enhanced vascular inosculation, increased bone formation, and improved mechanical stability compared to non-vascularized controls. These technological advancements collectively represent significant progress toward the clinical translation of engineered vascularized bone grafts capable of addressing complex and previously intractable bone defects. Full article

Cartilage and bone defects as well as osteoarthritis are prevalent worldwide, affecting individuals across all age groups, from young, active populations to older adults. The standard protocol in cartilage regeneration involves knee replacement surgery through the implantation of an endoprosthesis. Current clinical protocols involving cell-based therapies are associated with limitations, including the lack of functional cartilage-like tissue and dedifferentiation of chondrocyte, particularly during monoculture. Similarly, in bone regeneration, the “gold standard” is the use of bone auto- or allografts, which are associated with immunological rejection, inadequate vascularization, and limited osteogenesis. To overcome these limitations, various co-culture techniques have been introduced as promising strategies for cartilage and bone tissue regeneration. These systems aim to mimic native microenvironments by promoting interactions between chondrocytes and mesenchymal stromal cells (MSCs) in cartilage repair and between osteogenic and angiogenic cells in bone regeneration. This paper introduces different co-culture systems focusing on in vitro crosstalk between MSCs derived from various sources and other somatic cell populations in cartilage and bone regeneration. Full article

Background: The immune response is essential for bone regeneration, and macrophages in the immune microenvironment contribute to bone metabolism and angiogenesis. Emerging evidence demonstrates that simvastatin is a promising candidate for bone repair and promotes bone formation both in vitro and in vivo. However, the effect of simvastatin on macrophages and the following outcomes are still unclear. Objectives: This study aimed to investigate the potential immunomodulatory effect of simvastatin on M1 macrophages and its subsequent impact on osteogenesis and angiogenesis. Methods: Cell viability was assessed by CCK-8. Osteogenic and angiogenic markers were evaluated by RT-qPCR, Western blotting, and immunofluorescence. M1 macrophage phenotype was analyzed by flow cytometry. Osteogenesis was examined by histological staining, and angiogenic capacity was assessed using functional assays. Results: The present study found that simvastatin decreased M1 macrophage markers (CD86) and stimulated M1 macrophages to express high levels of pro-regenerative cytokines (BMP-2 and VEGF). In addition, simvastatin promoted osteogenic differentiation in MC3T3-E1 cells and angiogenic gene expression in HUVECs. Importantly, simvastatin enhanced the osteogenic capacity of MC3T3-E1 and the angiogenic potential of HUVECs by inhibiting M1 macrophage polarization in vitro. Conclusions: We demonstrated that simvastatin could confer favorable bone immunomodulatory properties and influence the crosstalk behavior between immune cells and osteoblasts and vascular endothelial cells to promote bone healing. Full article

Background: The rehabilitation of complex bone defects in the anterior maxilla presents significant challenges in restoring both function and esthetics. A multidisciplinary approach integrating guided bone regeneration (GBR) and connective tissue grafting (CTG) has proven effective in addressing such cases. Methods: This report describes the case of a 60-year-old female patient who presented with severe alveolar ridge resorption and peri-implant bone loss, necessitating an advanced regenerative strategy. The treatment protocol involved the use of autologous and xenogeneic bone grafts in combination with hyaluronic acid and polynucleotides to enhance osteogenesis and tissue integration. A six-month healing period was observed before histological and clinical evaluations were conducted. Results: The results demonstrated a significant increase in lamellar bone formation and vascularization in sites treated with biomodulators compared to conventional GBR techniques. Subsequently, CTG was employed to optimize peri-implant soft tissue volume and stability, leading to improved keratinized tissue thickness and enhanced esthetic outcomes. This case underscores the importance of a comprehensive surgical and prosthetic plan that integrates bone regeneration with mucogingival management for optimal results in implant rehabilitation. Additionally, histological analysis revealed that the incorporation of hyaluronic acid and polynucleotides resulted in improved cellular activity, reduced inflammatory responses, and enhanced overall bone quality. Conclusions: These results highlight the potential role of biomodulators in regenerative procedures. While the findings suggest promising clinical applications, further long-term studies are necessary to validate the outcomes and establish standardized protocols for the integration of advanced biomaterials in implantology. 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

The human bone is a dynamic, highly vascularized tissue composed of 60–70% minerals, which include mainly calcium phosphate (CaP) in the form of hydroxyapatite (HA) crystals, 30% organic matrix composed of type I collagen fibers, and less than 5% water and lipids. The crystals are formed inside the matrix vesicles (MVs) and are then released in the organic collagen-based fibrous matrix. Extracellular matrix (ECM) formation and mineralization processes, named osteogenesis, are associated with human mesenchymal stem cells (hMSCs) undergoing differentiation into osteoblasts (osteoblastogenesis). Osteogenesis is regulated by multiple intracellular signaling and genetic pathways and by environmental factors. Calcium flow is finely regulated and plays a key role in both osteoblastogenesis and osteogenesis. The formation and accumulation of CaP, the biogenesis of MVs, their secretion, and the deposition of HA crystals to fill the organic bone matrix are the fundamental events in the biomineralization process. In this paper, I will describe and discuss the recent findings and hypothesis on the molecular mechanism regulating this process. Full article

Osteogenesis–angiogenesis coupling, a dynamic and coordinated interaction between skeletal and vascular cells, is essential for fracture healing. However, the effects of these cell ratios and their interactions under microfluidic perfusion and paracrine signaling on osteogenesis–angiogenesis coupling have rarely been reported. In this study, dynamic and static models of osteogenesis–angiogenesis coupling were developed and the osteogenic and angiogenic effects of the two models were compared. Static co-cultures of MC3T3-E1 and bEnd.3 cells in Transwell inserts showed a cell ratio-dependent reciprocal relation: a ratio of 1:1 (MC3T3-E1:bEnd.3) favored osteogenesis, whereas a ratio of 2:1 (MC3T3-E1:bEnd.3) promoted angiogenesis. On that basis, we developed an osteogenesis–angiogenesis coupling chip based on microfluidic technology. The microfluidic perfusion within the chip further enhanced the mineralizing effect of osteoblasts and the angiogenic effect of endothelial cells, respectively, and increased the secretion of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) compared to the static Transwell insert model. The results suggest that the microfluidic chip enhanced the potential of osteogenesis–angiogenesis coupling mediated by paracrine signaling. Overall, the chip is not only a powerful model for understanding bone–vascular interaction but also a scalable platform for high-throughput drug screening and personalized therapy development for fractures. Full article

Polyetheretherketone (PEEK) is a widely used material in bone tissue engineering due to its favorable mechanical properties and radiolucency. However, its bioinert nature and lack of osteogenic activity restrict its ability to support effective bone regeneration. In this study, a novel APS-coated plasma-treated sulfonated bioactive PEEK scaffold (APS/PSBPK) was developed to overcome these limitations. The scaffold integrates strontium-doped bioactive glass (SrBG) to enhance biocompatibility and osteogenic potential, while astragalus polysaccharide (APS) was incorporated via plasma cleaning to modulate immune responses and promote vascularization. In vitro studies demonstrated that the APS/PSBPK scaffold facilitates M2 macrophage polarization, reduces pro-inflammatory cytokines, and enhances the secretion of anti-inflammatory factors. It also promotes endothelial cell migration and angiogenesis while supporting the adhesion, proliferation, and osteogenic differentiation of rBMSCs. In vivo experiments revealed that the scaffold effectively regulates the immune microenvironment, promotes vascularization, and accelerates bone regeneration. Thus, the APS/PSBPK composite scaffold serves as a multifunctional biomaterial with significant potential for applications in bone repair and regeneration by combining immunomodulation, angiogenesis, and osteogenesis. Full article

Introduction: The physiological process of wound healing is a complex and dynamic series of events that aims to restore damaged tissues to their original structure and function. Platelet-rich plasma (PRP), an autologous blood-derived product, is characterized by a high concentration of platelets suspended in a small volume of plasma, along with a complete array of coagulation factors at physiological concentrations. Beyond platelets, PRP contains a significant quantity of bioactive growth factors, such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-β), all of which are crucial mediators of tissue repair and osteogenesis. Due to these properties, PRP has garnered considerable attention in oral surgery, where the efficient regeneration of both hard and soft tissues is critical for the optimal therapeutic outcomes. Objectives: This systematic review aimed to critically evaluate the efficacy of PRP in oral surgical procedures, with particular emphasis on its role in the regeneration of both soft and hard tissues, as well as its clinical outcomes. Furthermore, the review sought to identify the diverse surgical applications of PRP and assess the impact of its use in conjunction with grafting materials on regenerative outcomes. Methods: A comprehensive systematic review was conducted, analyzing articles published within the last decade regarding the application of PRP in oral surgery, specifically focusing on periodontal, regenerative, and implant-related procedures. Studies were selected based on rigorous inclusion criteria, assessing the utilization of PRP across different clinical settings. Results: Thirteen relevant studies were included, which were categorized as follows: three studies involving implant surgery, three studies focusing on third molar extractions, two studies on regenerative surgery, two studies addressing periodontal surgery, one study examining intrabony periodontal defects, and two studies on ridge augmentation procedures. The majority of studies reported modest improvements in clinical parameters such as periodontal probing depth and clinical attachment level (CAL). Furthermore, significant positive outcomes were observed in soft tissue healing, with notable enhancements in bone density. These results suggest that PRP may facilitate the healing process, particularly in soft tissues, while also promoting bone regeneration to a degree. Conclusions: The findings of this systematic review underscore the potential of PRP as a valuable adjunct in oral surgery, demonstrating significant benefits in the regeneration of soft tissues and, to a lesser extent, hard tissues. Notably, the standalone application of PRP did not yield substantial improvements in regenerative outcomes. However, when PRP was used in combination with grafting materials, more pronounced benefits were observed, indicating a synergistic effect that enhances both soft and hard tissue regeneration. These findings support the rationale for incorporating PRP into clinical practice, particularly in conjunction with grafting materials, to optimize patient outcomes in oral surgery. Further research, particularly involving larger sample sizes and long-term follow-ups, is necessary to fully elucidate the optimal clinical applications and mechanistic pathways of PRP in oral regenerative procedures. Full article

Background/Objectives: A novel 3D-printed, bioresorbable bone graft, made of nanohydroxyapatite (nHAP) covered by poly(lactide-co-glycolide) (PLGA), showed strongly expressed osteoinductive properties in our previous investigations. The current study examines its application in the dual regeneration of bone and cartilage by combining with nHAP gel obtained by nHAP enrichment with hydroxyethyl cellulose, sodium hyaluronate, and chondroitin sulfate. Methods: In the in vitro part of the study, the mitochondrial activity and osteogenic and chondrogenic differentiation of stem cells derived from apical papilla (SCAPs) in the presence of nHAP gel were investigated. For the in vivo part of the study, three rabbits underwent segmental osteotomies of the lateral condyle of the femur, and defects were filled by 3D-printed grafts customized to the defect geometry. Results: In vitro study revealed that nHAP gel displayed significant biocompatibility, substantially increasing mitochondrial activity and facilitating the osteogenic and chondrogenic differentiation of SCAPs. For the in vivo part of the study, after a 12-week healing period, partial resorption of the graft was observed, and lamellar bone tissue with Haversian systems was detected. Histological and stereological evaluations of the implanted grafts indicated successful bone regeneration, marked by the infiltration of new bone and cartilaginous tissue into the graft. The existence of osteocytes and increased vascularization indicated active osteogenesis. The hyaline cartilage near the graft showed numerous new chondrocytes and a significant layer of newly formed cartilage. Conclusions: This study demonstrated that tailored 3D-printed bone grafts could efficiently promote the healing of substantial bone defects and the formation of new cartilage without requiring supplementary biological factors, offering a feasible alternative for clinical bone repair applications. Full article

Hierarchical porous hydrogels possess advantageous characteristics that facilitate cell adhesion, promote tissue growth, and enhance angiogenesis and osteogenesis. In this study, porous composite hydrogels were successfully prepared by a two-step gelation method with sodium alginate (SA), gelatin (GEL), and calcium hydrogen phosphate (DCP) as the main components. The fabricated porous hydrogels initially featured small pores (approximately 60 μm), and gradually evolved to large pores (exceeding 250 μm) during the gradual degradation in the cellular microenvironment. In vitro cell culture experiments indicated that these hydrogels could enhance the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells due to the hierarchical porous structure and the incorporation of DCP. Subcutaneous implantation and cranial defect repair experiments in Sprague−Dawley rats further confirmed that the small initial pore size of hydrogel scaffolds can provide more sites for cell adhesion. Additionally, the gradual degradation to form large pores was conducive to cell/tissue growth and blood vessel formation, ultimately being beneficial for vascularized bone regeneration. In summary, this study proposes an innovative strategy for developing porous hydrogels with gradual degradation for functional bone regeneration. Full article

The reconstruction of long bone defects after the primary traumatic, secondary infectious, or tumor-related loss of substance continues to represent a surgical challenge. Distraction osteogenesis using segmental transport, vascularized bone transfer, and the induced membrane technique (IMT) are established methods of reconstruction. IMT has become increasingly popular in recent decades due to its practicability, reproducibility, and reliability. At the same time, the original technique has undergone numerous modifications. The results are correspondingly heterogeneous. This article is intended to provide an overview of the current principles and modifications of IMT, outline the causes of failure of the IMT, and introduce the pearl-string technique (PST). The PST developed in our hospital is based on the pearl-string-like arrangement of thermodisinfected, decorticated femoral heads (TDFHs) in combination with a mechanically stable osteosynthetic construct. The TDFHs are biologically activated with either an RIA or autologous iliac crest bone graft. To gain a better understanding of these variations, the surgical technique of both procedures is illustrated step-by-step in this article. Full article

Background/Objectives: Limb lengthening and deformity correction techniques, particularly distraction osteogenesis, have significantly evolved in pediatric orthopedics. This study examines the temporal changes of key biochemical markers—vascular endothelial growth factor (VEGF), fibroblast growth factor 1 (FGF-1), and the propeptide of type I collagen (P1NP)—during the limb lengthening process. Methods: Twenty pediatric patients (aged 13–16) underwent distraction osteogenesis using the Circular Hexapod External Fixator. Peripheral blood samples were collected pre-treatment, three weeks after initiating distraction, and one month post-lengthening. Marker levels were measured using ELISA. Results: Serum VEGF concentrations significantly increased during treatment, peaking at T2 (T1 35.91 ± SD 5.54 vs. T2 293.47 ± SD 69.57, p < 0.0001), then declined at T3 (293.47 ± SD 69.57 vs. 40.86 ± SD 6.26, p < 0.0001). FGF-1 showed minor fluctuations initially but significantly increased by T3 (18.14 ± SD 4.57 vs. 41.56 ± SD 17.15, p < 0.01), about 2.3 times higher than baseline. P1NP concentrations exhibited a linear increase, with a significant rise from T2 to T3 (234.06 ± SD 36.57 vs. 280.68 ± SD 35.63, p < 0.05), while the T1 to T2 increase was not statistically significant, indicating ongoing osteoblastic activity and bone formation. Conclusions: This study highlights the dynamic changes in VEGF, FGF-1, and P1NP during distraction osteogenesis, emphasizing their roles as biomarkers of bone regeneration. These findings enhance the understanding of bone healing mechanisms and could inform future therapeutic strategies for pediatric limb lengthening. Further research is warranted to explore their clinical utility. Full article

This narrative review explores the potential effects of Propolis and its bioactive compounds on bone health. Propolis, a resinous product collected by bees, is renowned for its antimicrobial, anti-inflammatory, and antioxidant properties. Recent research emphasizes its positive role in osteogenesis, primarily through the modulation of osteoclast and osteoblast activity via molecular pathways. Key mechanisms include reducing inflammatory cytokines, protecting against oxidative stress, and upregulating growth factor essential for bone formation. While compounds such as Caffeic Acid Phenethyl Ester, Apigenin, Quercetin, and Ferulic Acid have been well-documented, emerging evidence points to the significant roles of less-studied compounds like Pinocembrin, Kaempferol, p-Coumaric acid, and Galangin. This review synthesizes the current literature, focusing on the mechanisms by which these bioactive compounds influence osteogenesis. Firstly, it explores the techniques for characterizing bioactive compounds presented in propolis, the chemogeographic variations in its composition, and the effects of both crude extracts and isolated compounds on bone tissue, offering a comprehensive analysis of recent findings across different experimental models. Further, it discusses the effects of Propolis compounds on bone health. In summary, these compounds modulate signaling pathways, including nuclear factor kappa beta, wingless-related integration site, mitogen-activated protein kinase, vascular endothelial growth factor, and reactive oxygen species. These pathways influence the receptor activator of nuclear factor kappa-β/receptor activator of nuclear factor kappa-β ligand/osteoprotegerin system, fostering bone cell differentiation. This regulation mitigates excessive osteoclast formation, stimulates osteoblast activity, and ultimately contributes to the restoration of bone homeostasis by maintaining a balanced bone remodeling process. Full article