Search Results (95)

Bone is a preferred site for disseminated tumor cells, yet the molecular mechanisms that prepare the skeletal microenvironment for metastatic colonization are only beginning to be understood. At the heart of this process are extracellular vesicles (EVs), nano-sized, lipid-encapsulated particles secreted by cancer cells and stromal components. This review consolidates current findings that position EVs as key architects of the bone-metastatic niche. We detail the biogenesis of EVs and their organotropic distribution, focusing on how integrin patterns and bone-specific ligands guide vesicle homing to mineralized tissues. We then outline the sequential establishment of the pre-metastatic niche, driven by EV-mediated processes including fibronectin deposition, stromal cell reprogramming, angiogenesis, neurogenesis, metabolic reconfiguration, and immune modulation, specifically, the expansion of myeloid-derived suppressor cells and impaired lymphocyte function. Within the bone microenvironment, tumor-derived EVs carrying microRNAs and proteins shift the balance toward osteoclastogenesis, inhibit osteoblast differentiation, and disrupt osteocyte signaling. These alterations promote osteolytic destruction or aberrant bone formation depending on tumor type. We also highlight cutting-edge imaging modalities and single-EV omics technologies that resolve EV heterogeneity and identify potential biomarkers detectable in plasma and urine. Finally, we explore therapeutic approaches targeting EVs, such as inhibition of nSMase2 or Rab27A, extracorporeal EV clearance, and delivery of engineered, bone-targeted vesicles, while addressing translational challenges and regulatory considerations. This review offers a roadmap for leveraging EV biology in predicting, preventing, and treating skeletal metastases by integrating advances across basic biology, bioengineering, and translational science. Full article

This research activity proposes to produce composite hydrogel–bioactive glass. The primary purpose of this research is to develop and optimize 3D-printed scaffolds using doped bioglass, aimed at enhancing bone regeneration in bone defects. The bioglass, a bioactive material known for its bone-bonding ability (SiO₂–P₂O₅–CaO–Na₂O), co-doped with europium and silver was synthesized and doped to improve its biological properties. This doped bioglass was then combined with a biocompatible hydrogel, chosen for its adequate cellular response and printability. The composite material was printed to form a scaffold, providing a structure that not only supports the damaged bone but also encourages osteogenesis. A variety of methods were employed to assess the rheological, compositional, and morphological characteristics of the samples: Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) coupled with energy-dispersive X-ray spectroscopy (EDS). Additionally, simulated body fluid (SBF) immersion for bioactivity monitoring and immunocytochemistry for cell viability were used to evaluate the biological response of the scaffolds. Full article

Critical-sized bone defects (CSBDs) are injuries that exceed the body’s natural capacity for repair and require external intervention. These defects are particularly challenging in the mandible, often resulting from trauma, tumor resection, or implant-related complications. Effective treatment involves scaffold designs that support vascularization, bone formation, and sufficient mechanical strength. This systematic review aims to assess whether ceramic-based scaffold properties, including porosity, pore size, and macroscopic characteristics, improve vascularization, bone formation, and the mechanical properties in the treatment of CSBDs in large animal models. A search of databases (PubMed, Embase, and Web of Science) identified 11 in vivo studies involving CSBDs (>2 cm), ceramic scaffolds, and histological analysis. Findings indicate that scaffolds with porosity exceeding 50% yield optimal outcomes by striking a balance between cell infiltration and mechanical stability. Pore sizes ranging from 300 μm to 700 μm are ideal for vascularization and bone ingrowth. Three-dimensional (3D) printing shows promise in creating scaffolds with precise and reproducible features. However, the studies varied significantly in their methodologies and outcomes, with no consensus on the optimal scaffold properties for mandibular CSBDs. Scaffold porosity and pore size play key roles in promoting vascularization and bone regeneration. Various animal models reinforce this finding, suggesting that scaffold architecture is crucial for biological integration and functional outcomes. This review highlights the importance of standardized research protocols and clear design criteria in enhancing the success of bone regeneration. Future research should investigate emerging biomaterials and new scaffold technologies to overcome current limitations in clinical applications. Full article

Inflammatory arthritis, including rheumatoid arthritis (RA) and osteoarthritis (OA), is a group of degenerative joint diseases that result in reduced mobility and a prevalent cause of disability. Despite differing etiologies, both conditions involve inflammation, affecting only the joints in OA and systemic in RA due to its autoimmune nature. Regenerative medicine offers promising alternatives, with a focus on the therapy with mesenchymal stem cell (MSC) and their secreted extracellular vesicles (EVs). MSC-derived EVs have shown great potential in modulating inflammatory pathways and promoting tissue repair in the preclinical models of RA and OA. Additionally, EVs from immune cells exhibit strong anti-inflammatory effects, reducing cartilage and bone degeneration. This review highlights the recent progress in MSC-based and EV-based therapies for OA and RA, discussing the bioengineering approaches that enhance the therapeutic efficacy, stability, and targeting of EV. It also addresses the major challenges in translating EV therapy from the laboratory to clinical practice and discusses strategies to overcome these obstacles in the treatment of inflammatory arthritis. Full article

Artificial intelligence (AI) is revolutionizing the field of orthopedic bioengineering by increasing diagnostic accuracy and surgical precision and improving patient outcomes. This review highlights using AI for orthopedics in preoperative planning, intraoperative robotics, smart implants, and bone regeneration. AI-powered imaging, automated 3D anatomical modeling, and robotic-assisted surgery have dramatically changed orthopedic practices. AI has improved surgical planning by enhancing complex image interpretation and providing augmented reality guidance to create highly accurate surgical strategies. Intraoperatively, robotic-assisted surgeries enhance accuracy and reduce human error while minimizing invasiveness. AI-powered smart implant sensors allow for in vivo monitoring, early complication detection, and individualized rehabilitation. It has also advanced bone regeneration devices and neuroprosthetics, highlighting its innovation capabilities. While AI advancements in orthopedics are exciting, challenges remain, like the need for standardized surgical system validation protocols, assessing ethical consequences of AI-derived decision-making, and using AI with bioprinting for tissue engineering. Future research should focus on proving the reliability and predictability of the performance of AI-pivoted systems and their adoption within clinical practice. This review synthesizes recent developments and highlights the increasing impact of AI in orthopedic bioengineering and its potential future effectiveness in bone care and beyond. Full article

Natural biomaterials have gained significant attention in modern dentistry due to their biocompatibility, biodegradability, and low immunogenicity. These materials, including alginate, cellulose, chitosan, collagen, and hydroxyapatite, have been widely explored for their applications in stomatology. They play a crucial role in periodontal disease treatment, caries prevention, and implantology, providing an alternative to synthetic materials. Natural polymers such as chitosan and cellulose are utilized in drug delivery systems and tissue regeneration, while hydroxyapatite serves as a bone substitute due to its osteoconductive properties. Collagen-based scaffolds and coatings enhance periodontal and bone tissue regeneration. Additionally, bioengineered and chemically modified biomaterials offer improved mechanical and biological characteristics, expanding their clinical applications. This review aims to provide a comprehensive analysis of the biological properties, advantages, and limitations of selected natural biomaterials in dentistry. It explores their applications in various aspects of stomatology, including periodontal disease prevention and regeneration, dental caries prevention, bone substitutes in implantology, and dental implant coating. Although natural biomaterials exhibit promising properties, further research is necessary to refine their performance, enhance stability, and ensure long-term safety. Advancements in nanotechnology and bioengineering continue to drive the development of innovative natural biomaterials, paving the way for more effective and biocompatible dental therapies. Full article

Advanced bioengineering, popularly known as regenerative dentistry, has emerged and is steadily developing with the aim of replacement of lost or injured tissues in the mouth using stem cells and other biomaterials. Conventional therapies for reparative dentistry, for instance fillings or crowns, mainly entail the replenishment of affected tissues without much concern given to the regeneration of tissues. However, these methods do not enable the natural function and aesthetics of the teeth to be maintained in the long term. There are several regenerative strategies that offer the potential to address these limitations to the extent of biologically restoring the function of teeth and their components, like pulp, dentin, bone, and periodontal tissues. Hence, stem cells, especially dental tissue derived stem cells, such as dental pulp stem cells, periodontal ligament stem cells, or apical papilla stem cells, are quite promising in this regard. These stem cells have the potentiality of generating precise dental cell lineages and thus are vital for tissue healing and renewal. Further, hydrogels, growth factors, and synthetic scaffolds help in supporting the stem cells for growth, proliferation, and differentiation into functional tissues. This review aims at describing the process of stem cell-based tissue repair biomaterials in dental regeneration, and also looks into the practice and prospects of regenerative dentistry, analysing several case reports and clinical investigations that demonstrate the efficacy and limitations of the technique. Nonetheless, the tremendous potential for regenerative dentistry is a reality that is currently challenged by biological and technical constraints, such as scarcity of stem cell sources, inadequate vascularization, and the integration of the materials used in the procedure. As we move forward, the prospects for regenerative dentistry are in subsequent developments of stem cell technology, biomaterial optimization, and individualized treatment methods, which might become increasingly integrated in dental practices globally. However, there are regulatory, ethical and economic issues that may pose a hurdle in the further advancement of this discipline. Full article

Current treatment methods for critical bone defects involve the implantation of large bone grafts, which are limited by tissue availability and failure to heal correctly with high complication rates. Bioengineered scaffolds have emerged, which deploy biodegradable, highly osteoconductive materials in porous structures to accommodate the high mass transport requirements of large bone defects. Ideal scaffold biomaterials require a balance between strength, composition, and osteoconduction, a balance which has yet to be discovered. Naturally derived materials like deproteinized bovine bone mineral (DBBM) have seen successful clinical use for decades as bone void fillers, but their granular or putty form lacks the interconnected porosity required to treat large defects. Leveraging the clinical success of DBBM, this paper presents the first fabrication of highly porous scaffolds composed of naturally derived, deproteinized bone mineral, for potential use in large bone defects. Ovine bone mineral powder was prepared from fresh ovine bone, fabricated into a photopolymeric slurry and 3D-printed using a photocasting process into 67% porous gyroid scaffolds. Ovine bone mineral composition, surface microstructure, compressive properties, and failure probability were evaluated and compared to gyroid scaffolds composed of tricalcium phosphate. Both scaffold types were similar, with characteristics in the low range of human cancellous bone. Full article

Scaffolds are critical in regenerative medicine, particularly in bone tissue engineering, where they mimic the extracellular matrix to support tissue regeneration. Scaffold efficacy depends on precise control of 3D printing parameters, which determine geometric and mechanical properties, including Young’s modulus. This study examines the impact of nozzle temperature, printing speed, and feed rate on the Young’s modulus of polylactic acid (PLA) scaffolds. Using a Prusa MINI+ 3D printer (Prusa Research a.s., Prague, Czech Republic), systematic experiments are conducted to explore these correlations. Results show that higher nozzle temperatures decrease Young’s modulus due to reduced viscosity and weaker interlayer bonding, likely caused by thermal degradation and reduced crystallinity. Printing speed exhibits an optimal range, with Young’s modulus peaking at moderate speeds (around 2100 mm/min), suggesting a balance that enhances crystallinity and bonding. Material feed rate positively correlates with Young’s modulus, with increased material deposition improving scaffold density and strength. The integration of an Artificial Neural Network (ANN) model further optimized the printing parameters, successfully predicting the maximum Young’s modulus while maintaining geometric constraints. Notably, the Young’s modulus achieved falls within the typical range for cancellous bone, indicating the model’s potential to meet specific clinical requirements. These findings offer valuable insights for designing patient-specific bone scaffolds, potentially improving clinical outcomes in bone repair. Full article

Background/Objectives: Computer-assisted mandibular reconstruction requires sophisticated technical expertise alongside surgical knowledge. This study aims to establish and validate an efficient collaborative protocol between oral and maxillofacial surgeons and bioengineers for virtual surgical planning in mandibular reconstruction. Methods: We developed a structured protocol with four sequential phases: (1) generation of 3D models from CT data, (2) virtual resection planning, (3) reconstruction design, and (4) surgical guide fabrication. Protocol efficiency was assessed through seven simulation trials measuring planning duration and required revisions. Clinical validation was performed in four mandibular reconstruction cases. Accuracy was evaluated by comparing virtual surgical plans to postoperative outcomes using 3-matic 13.0 software analysis. Results: Protocol implementation showed consistent efficiency across simulations with a mean planning duration of 2.86 working days (SD = 1.35). Only two of seven simulations required design revisions. Clinical application in four cases (three ameloblastomas, one odontogenic myxoma) demonstrated high precision with a mean virtual-to-actual discrepancy of 0.90 mm (SD = 0.34). Successful reconstructions were achieved across varying defect spans (29–53 mm) using both bicortical deep circumflex iliac artery (DCIA) flaps and monocortical iliac block bone grafts. The collaborative workflow resulted in optimized surgical guide design, reduced planning iterations, and improved surgical precision. Conclusions: The established surgeon–bioengineer collaborative protocol enhances the efficiency and accuracy of computer-assisted mandibular reconstruction while making advanced surgical planning techniques more accessible. While initial results are promising, future studies with larger patient cohorts and extended follow-up periods are needed to fully validate the protocol’s long-term benefits and broader applicability. Full article

Transplantation of decellularized uterus tissue showed promise in supporting regeneration following uterine injury in animal models, suggesting an alternative to complete uterus transplantation for uterine factor infertility treatment. However, most animal studies utilized small grafts, limiting their clinical relevance. Hence, we used larger grafts (20 × 10 mm), equivalent to nearly one uterine horn in rats, to better evaluate the bioengineering challenges associated with structural support, revascularization, and tissue regeneration. We analyzed histopathology, employed immunohistochemistry, and investigated gene expression discrepancies in growth-related proteins over four months post-transplantation in acellular grafts and those recellularized (RC) with bone marrow-derived mesenchymal stem cells (bmMSCs). RC grafts exhibited less inflammation and faster epithelialization and migration of endogenous cells into the graft compared with acellular grafts. Despite the lack of a significant difference in the density of CD31 positive blood vessels between groups, the RC group demonstrated a better organized myometrial layer and an overall faster regenerative progress. Elevated gene expression for Vegf, Cd44, and Itgb1 correlated with the enhanced tissue regeneration in this group. Elevated Tgfb expression was noted in both groups, potentially contributing to the rapid revascularization. Our findings suggest that large uterine injuries can be regenerated using decellularized tissue, with bmMSCs enhancing the endogenous repair mechanisms. Full article

With the current state of knowledge regarding disorders of facial bone development, including anodontia, the development of a suitable animal model for preclinical studies is essential. The agenesis of dental buds occurs in about 25% of the human population. Prospects for treatment include the use of growth factors, stem cells, and bioengineering. This study aimed to investigate the influence of a tooth absence on facial bone growth, develop a technique for the application of growth factors to the developing bone, and analyze the comparative effect of the application of selected active proteins on the growth of the maxilla and mandible. Piglets underwent germectomy, followed by computed tomography and X-ray; morphometric and histological analyses of the bones were performed, blood bone morphogenetic protein 2 and platelet-derived growth factor concentrations were determined, and the transcriptomic profile of the dentate ligament was analyzed using DNA microarrays. It was not possible to identify the most effective growth factor application algorithm for achieving normal jaw development. Normal mandibular bone structure and oral mucosa structure were observed in the germectomy groups with growth factor augmentation. The average height of the mandibular alveolar part in the area of the removed dental buds was significantly lower compared with that of the inoperable side, 3 months after surgery. However, no significant differences were found in the serum concentrations of BMP-2 and PDGF between groups. The animal model of bone development disorders (including anodontia) developed in the current study and the scheme for evaluating the efficacy and safety of the application of replacement therapy for craniofacial malformations are important in the development of the discipline and represent an important contribution to the introduction of treatment methods. Full article