Search Results (766)

Background: The role of collagen membrane fixation during guided bone regeneration (GBR) remains debatable, particularly in post-extraction sockets with buccal defects and concomitant immediate implant placement. This study evaluated whether or not fixation with titanium pins improved regenerative outcomes. Methods: Six adult Beagle dogs received bilateral extractions of the fourth mandibular premolars. An implant was immediately placed in both the distal alveoli, and standardized buccal bone defects (5 mm height, 3–2 mm width) were prepared. All defects were filled with a slowly resorbing equine xenograft and covered by a resorbable pericardium membrane. At the test sites, the membrane was apically fixed with pins, while no fixation was applied to the control sites. After 3 months of healing, histomorphometric analyses were performed. Results: The vertical bone gain of the buccal crest was 3.2 mm in the test sites (pin group) and 2.9 mm in the control sites (no-pin) (p > 0.754). No significant difference was found in terms of bone-to-implant contact (BIC). However, residual graft particles were located significantly more coronally in the pin group compared to the no-pin group (p = 0.021). Morphometric analyses revealed similar new bone formation within the groups, but with higher amounts of residual xenograft and soft tissue in the pin group. Conclusions: Membrane fixation did not significantly enhance vertical bone gain, and although the slightly higher regeneration in the pin group (3.2 mm vs. 2.9 mm) may hold clinical relevance in esthetically sensitive areas and osseointegration, it appeared to limit coronal migration of the grafting material. Full article

This study evaluated the effects of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) coating in combination with vacuum plasma treatment on titanium implants, aiming to enhance osseointegration and bone regeneration while minimizing the adverse effects associated with high-dose rhBMP-2. In vitro analyses demonstrated that plasma treatment increased surface energy, promoting cell adhesion and proliferation. Additionally, it facilitated sustained rhBMP-2 release by enhancing protein binding to the implant surface. In vivo experiments using the four-beagle mandibular defect model were conducted with the following four groups: un-treated implants, rhBMP-2–coated implants, plasma-treated implants, and implants treated with both rhBMP-2 and plasma. Micro-computed tomography (micro-CT) and medical CT analyses revealed a significantly greater volume of newly formed bone in the combined treatment group (p < 0.05). Histological evaluation further confirmed superior outcomes in the combined group, showing significantly higher bone-to-implant contact (BIC), new bone area (NBA), and inter-thread bone density (ITBD) compared to the other groups (p < 0.05). These findings indicate that vacuum plasma treatment enhances the biological efficacy of low-dose rhBMP-2, representing a promising strategy to improve implant integration in compromised conditions. Further studies are warranted to determine the optimal clinical dosage. Full article

This study evaluated the bone regeneration effect and mechanical properties of “Sticky bone”, a mixture of platelet-rich fibrin (PRF) and synthetic bone grafts (SBGs), in the repair of large femoral bone defects in rabbits. Eighteen New Zealand white rabbits were included and randomly divided into a Sticky bone group and an SBG alone group. Bone graft samples were collected and analyzed at 4, 8, and 12 weeks after surgery. Micro- computed tomography (CT) analysis showed that the amount of the Sticky bone group in the grayscale ranges of 255–140 (highly mineralized tissue or unabsorbed bone powder) and 140–90 (representing new cancellous bone) was higher than that of the SBG group at each time point and decreased with the number of weeks. The compression strength test showed that the average compression strength of the Sticky bone group reached 5.17 MPa at the 12th week, which was 1.62 times that of the intact bone (3.19 MPa) and was significantly better than that of the SBG group (about 4.12 MPa). This study also confirmed for the first time that the use of a new polyethylene terephthalate (PET) blood collection tube to prepare PRF can stably release key growth factors such as platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor (VEGF), which are conducive to early bone vascularization and cell proliferation. In summary, Sticky bone has the potential to promote bone formation, enhance tissue integration and mechanical stability, and can be used as an effective alternative material for repairing large-scale bone defects in clinical practice in the future. Full article

Plant-derived vesicle-like nanoparticles (PDVLNs) are bioactive nanovesicles secreted by plant cells, emerging as a novel therapeutic tool for tissue repair and regeneration due to their low immunogenicity, intrinsic bioactivity, and potential as drug delivery carriers. This review examines PDVLNs’ biogenesis mechanisms, isolation techniques, and compositional diversity, emphasizing their roles in promoting essential regenerative processes—cell proliferation, differentiation, migration, immune modulation, and angiogenesis. We explore their therapeutic applications across multiple tissue types, including skin, bone, neural, liver, gastrointestinal, cardiovascular, and dental tissues, using both natural and engineered PDVLNs in various disease models. Compared to mammalian exosomes, PDVLNs offer advantages such as reduced immune rejection and ethical concerns, enhancing their sustainability and appeal for regenerative medicine. However, challenges in clinical translation, including scalability, standardization, and safety remain. This paper consolidates current knowledge on PDVLNs, highlighting their versatility and providing insights into engineering strategies to optimize efficacy, ultimately outlining future research directions to advance their clinical potential. Plant vesicle-like nanoparticles (PDVLNs) may become a new avenue for the treatment of tissue injury, promoting tissue repair and regeneration through their intrinsic bioactivity or as drug delivery carriers. In addition, PDVLNs can be engineered and modified to achieve better results. Full article

Plasma-derived fibrin hydrogels are widely used in tissue engineering because of their excellent biological properties. Specifically, human plasma-derived fibrin hydrogels serve as 3D matrices for autologous skin graft production, skeletal muscle repair, and bone regeneration. Nevertheless, for advanced applications such as in vitro skin equivalents and engineered grafts, the intrinsic limitations of native fibrin hydrogels in terms of long-term mechanical stability and resistance to degradation need to be addressed to enhance the usefulness and application of these hydrogels in tissue engineering. In this study, we chemically modified plasma-derived fibrin by incorporating succinimidyl alginate (SA), a version of alginate chemically modified to introduce reactive succinimidyl groups. These NHS ester groups (N-hydroxysuccinimide esters), attached to the alginate backbone, are highly reactive toward the primary amine groups present in plasma proteins such as fibrinogen. When mixed with plasma, the NHS groups covalently bond to the amine groups in fibrin, forming stable amide linkages that reinforce the fibrin network during hydrogel formation. This chemical modification improved mechanical properties, reduces contraction, and enhanced the stability of the resulting hydrogels. Hydrogels were prepared with a final fibrinogen concentration of 1.2 mg/mL and SA concentrations of 0.5, 1, 2, and 3 mg/mL. The objective was to evaluate whether this modification could create a more stable matrix suitable for supporting skin tissue development. The mechanical and microstructure properties of these new hydrogels were evaluated, as were their biocompatibility and potential to create 3D skin models in vitro. Dermo-epidermal skin cultures with primary human fibroblast and keratinocyte cells on these matrices showed improved dermal stability and better tissue structure, particularly SA concentrations of 0.5 and 1 mg/mL, as confirmed by H&E (Hematoxylin and Eosin) staining and immunostaining assays. Overall, these results suggest that SA-functionalized fibrin hydrogels are promising candidates for creating more stable in vitro skin models and engineered skin grafts, as well as for other types of engineered tissues, potentially. 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

The increasing incidence of osteoporotic fractures determines ongoing research on new methods and strategies for improving the difficult healing process of this type of fracture. Osteoporotic patients suffer from the intense side effects of accustomed drug treatment and its systemic distribution in the body. To overcome these drawbacks, besides searching for new drugs, 3D-printed scaffolds and drug delivery systems have started to be increasingly seen as the main strategy employed against osteoporosis. Three-dimensionally printed scaffolds can be tailored in intricate designs and make use of nanoscale topographical and biochemical cues able to enhance bone tissue regeneration. Research regarding drug delivery systems is exploring bold new ways of targeting bone tissue, making use of designs involving nanoparticles and intricate encapsulation and support methods. The local administration of treatment with the help of a scaffold-based drug delivery system looks like the best option through its use of the advantages of both structures. Biomimetic systems are considered the future norm in the field, while stimuli-responsiveness opens the door for the next level of efficiency, patient compliance, and a drastic reduction in side effects. The successful approval of these products still requires numerous challenges throughout the development and regulatory processes, but the interest and effort in this direction are high. This review explored various strategies for managing osteoporosis, emphasizing the use of scaffolds for targeted drug delivery to bone tissue. Instead of covering the whole subject, we focused on the most important aspects, with the intention to provide an up-to-date and useful introduction to the management of osteoporosis. Full article

A varied family of polyphenolic chemicals, flavonoids, are becoming more and more important in bone tissue engineering because of their osteogenic, anti-inflammatory, and antioxidant effects. Recent developments incorporating flavonoids into different biomaterial platforms to improve bone regeneration are emphasized in this study. Osteocalcin (OCN) expression was 2.1-fold greater in scaffolds loaded with flavonoids—such as those made of polycaprolactone (PCL)—greatly increasing human mesenchymal stem cell (hMSC) proliferation and mineralization. Comparably, a threefold increase in calcium deposition indicates increased mineralization when hydroxyapatite (HA) was functionalized with flavonoids such as quercetin. These HA scaffolds with flavonoids also showed a 45% decrease in osteoclast activity, therefore promoting balanced bone remodeling. Concurrent with flavonoids like EGCG and quercetin, chitosan-based scaffolds encouraged osteogenic differentiation with increases in osteogenic markers like osteopontin (OPN) and alkaline phosphatase (ALP) expression by up to 82%. These scaffolds also showed 82% bone defect repair after six weeks in vivo, suggesting their promise in rapid bone regeneration. With an increase of up to 32% in the bone volume-to-total volume ratio (BV/TV) and 28% greater bone–implant contact (BIC), flavonoid coatings on titanium implants enhanced osteointegration in implantology. Displaying successful osteogenesis and immunomodulation, the addition of flavonoids into metal–organic frameworks (MOFs) and injectable hydrogels demonstrated a 72% increase in new bone formation in vivo. Though further research is required to confirm long-term clinical effectiveness, these findings show the great promise of flavonoid-functionalized biomaterials in bone regeneration. Full article

Background: The combination of polynucleotides and hyaluronic acid with bovine bone grafts in maxillary sinus lift procedures appears to be a promising strategy to enhance bone regeneration. This study aimed to analyze implant osseointegration, bone repair and sinus mucosa integrity using Bio-Oss^® and Hyaluronic Acid-Polynucleotide Gel (Regenfast^®) in maxillary sinus augmentation in rabbits. Methods: Sinus floor elevation was performed in 12 rabbits, with one implant placed per sinus simultaneously. In the control group, sinuses were grafted with deproteinized bovine bone mineral (Bio-Oss^®) alone; in the test group, Bio-Oss^® was combined with Regenfast^®. Two histological slides were obtained per sinus after 2 weeks (six animals) and 10 weeks (six animals): one from the grafted area alone (non-implant sites), and one from the implant site. Primary outcome variables included the percentage of newly formed bone, the extent of implant osseointegration, and the number of sinus mucosa perforations caused by contact with graft granules. Results: After 10 weeks of healing, the test group showed a significantly higher percentage of new bone formation (37.2 ± 6.7%) compared to the control group (26.8 ± 10.0%; p = 0.031); osseointegration extended to the implant apex in both groups; fewer sinus mucosa perforations were observed in the test group (n = 5) than in the control group (n = 14). Conclusions: The addition of Regenfast^® to Bio-Oss^® granules promoted enhanced bone regeneration within the elevated sinus area and was associated with a lower incidence of sinus membrane perforations compared to the use of Bio-Oss^® alone. 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

Background/Objectives: Angiogenesis is the multistep process of the formation of new blood vessels. It is beneficial in scenarios that require tissue repair and regeneration, such as wound healing, bone fracture repair, and recovery from ischemic injuries like stroke, where new blood vessel formation restores oxygen and nutrient supply to damaged areas. Extremely low-frequency electromagnetic stimulation (ELF-EMS), which involves electromagnetic fields in the frequency range of 0–300 Hz, have been shown to reduce ischemic stroke volume by improving cerebral blood flow and recovery effects that are dependent on eNOS. Based on previous results, we herein explore the effects of ELF-EMS treatment (13.5 mT/10 and 60 Hz) on the activation of angiogenic processes in vitro in homeostatic conditions. Methods: Using human microvascular endothelial cells (HMEC-1), we studied cell proliferation, migration, and tube formation in vitro, as well as nitric oxide production and the effect of calcium and nitric oxide (NO) on these processes. Moreover, blood vessel formation was studied using a chicken chorioallantoic membrane (CAM) assay. Results: Our results showed that ELF-EMS increases proliferation, tube formation, and both the migration and transmigration of these cells, the latter of which was mediated via NO. In turn, calcium inhibition decreased ELF-EMF-induced NO production. Furthermore, ELF-EMS significantly increased blood vessel formation in the CAM assay. Conclusions: Our results indicated that ELF-EMS exposure (13.5 mT/10 and 60 Hz) significantly induces angiogenesis in vitro and in ovo, underscoring its potential application in the treatment of conditions characterized by insufficient blood supply. Full article

Background: Resorbable biopolymers are increasingly explored for use in regenerative procedures within dental surgery. Their ability to degrade naturally, minimize surgical reinterventions, and potentially reduce immunogenicity makes them appealing in guided bone and tissue regeneration applications. However, despite these advantages, uncertainties persist regarding their comparative effectiveness and associated risks. For example, polyethylene glycol (PEG)-based membranes have shown comparable outcomes to porcine-derived collagen membranes in bone regeneration procedures, yet studies have reported a higher incidence of soft tissue healing complications associated with PEG-based materials. Similarly, while polycaprolactone (PCL) and dextrin-based hydrogels have demonstrated promising clinical handling and bone fill capabilities, their long-term performance and consistency across different anatomical sites remain under investigation. These findings highlight the need for further well-powered clinical trials to establish standardized guidelines for their safe and effective use. Methods: A systematic review protocol was registered with the PROSPERO database and developed in alignment with PRISMA guidelines. Database searches were conducted in PubMed, Medline, Scopus, and Cochrane from June to December 2024. Only randomized controlled trials (RCTs) focusing on synthetic resorbable biopolymers in bone augmentation procedures were considered. Bias was evaluated using the Cochrane Risk of Bias tool. Results: Eleven RCTs were included, totaling 188 patients. The findings suggest that materials such as polylactic acid (PLA), polycaprolactone (PCL), and polyethylene glycol (PEG) contributed effectively to new bone formation. PEG-based membranes were found to perform on par with or occasionally better than traditional collagen membranes derived from porcine sources. Additionally, the application of 3D-printable polymers demonstrated promise in site-specific healing. Conclusions: Resorbable biopolymers are effective and safe for GBR procedures, with clinical outcomes comparable to traditional materials. Advances in 3D-printing technology and bioactive coatings may further enhance their regenerative potential. However, the incidence of soft tissue healing complications suggests the need for further long-term studies to optimize material properties and clinical application. Full article

Background and Clinical Significance: To describe the effectiveness of alveolar ridge preservation under the radiological and histological analysis of a customized resorbable scaffold three-dimensionally printed with polycaprolactone (PCL) reinforced with a coating of a copolymer of polycaprolactone-block-polyethylene glycol (PCL–PEG) by electrospray. Case Presentation: A 62-year-old male with vertical root fractures of teeth #14 and #15. From the cone beam CT (CBCT) image, the scaffold root replicas were designed with the shape of the roots and printed with PCL coated with PCL–PEG by electrospray. The scaffold was inserted into the alveolar bone and maintained with a tension-free flap closure. After six months, a CBCT of the surgical site and histological analysis of a bone sample at the dental implant installation site were performed. After 6 months, the wound in tooth #14 was closed, clinically proving no adverse reaction or complications. The histological analysis of the bone sample showed new bone formation with lamellar structure, Haversian canal structure, and osteocyte spaces. However, the scaffold in tooth #15 was exposed and not osseointegrated, and it was covered with membranous tissue. Histologically, the sample showed tissue compatible with lax connective tissue with mixed inflammatory infiltrate. In tooth #14, the dental implant presented an insertion torque >35 Ncm and was rehabilitated three months after its installation. Conclusions: Three-dimensional printed PCL scaffolds showed the ability to regenerate vital and functional bone with osseointegration capability for maxillary bone regeneration and oral rehabilitation based on dental implants. A case of inadequate scaffold osseointegration accompanied by lax connective tissue formation is shown. Full article

The fundamental goal of endodontic surgery is to remove the infection cause and create an ideal environment for periapical tissue and bone recovery. This systematic review aims to present evidence-based findings regarding the healing ability of endodontic materials in retrograde treatment. The study evaluates the advantages and drawbacks of commonly utilized materials, empowering clinicians with valuable insights for preoperative planning in endodontic surgery. A comprehensive search was conducted across multiple databases, including MEDLINE, Scielo, Web of Science, Scopus, Embase, and Google Scholar, using the PIOT framework. A total of 3124 papers were identified, of which 2534 remained after removing duplicates. Following a stringent selection process, 35 clinical studies were included for qualitative assessment. The risk of bias was assessed using the Risk of Bias in Non-randomized Studies—of Interventions (ROBINS-I) tool for non-randomized trials, the Newcastle–Ottawa Scale for cohort studies, and the Joanna Briggs Institute (JBI) critical appraisal checklist for cross-sectional studies. Due to high heterogeneity in study designs and outcomes, a meta-analysis could not be performed. The review identified Super Ethoxybenzoic Acid (Super EBA), Mineral Trioxide Aggregate (MTA), and Intermediate Restorative Material (IRM^®), Retroplast, Endosequence^®, and gutta-percha as the primary retrograde root filling materials. Follow-up periods ranged from 6 months to 17.5 years. Although the materials showed varying degrees of success, the overall findings highlighted that no single material demonstrated universally superior healing ability. The review also emphasized the need for standardization in future clinical trials to facilitate better comparisons. The selection of retrograde filling materials plays a pivotal role in the success of endodontic surgery. New bioceramic materials like MTA and Biodentine offer improved sealing, biocompatibility, and tissue regeneration compared to traditional materials, leading to better clinical outcomes. Full article

Every year, millions of people worldwide suffer from bone tissue damage caused by bone trauma and surgical operations, as well as diseases such as osteoporosis, osteoarthritis, osteomyelitis, and periodontitis. Bone defect repair is one of the major challenges in the field of regenerative medicine. Although bone grafts are the gold standard for treating bone defects, factors such as donor sources and immune responses limit their application. Functionalized nanomaterials have become an effective means of treating bone diseases due to their good biocompatibility and osteoinductivity, anti-inflammatory, and antibacterial properties. Metal–organic frameworks (MOFs) are porous coordination polymers composed of metal ions and organic ligands, featuring unique physical properties, including a high surface area–volume ratio and porosity. In regenerative medicine, MOFs function as the functions of drug carriers, metal ion donors, nanozymes, and photosensitizers. When combined with other functional materials, they regulate cellular reactive oxygen species, macrophage phenotypic transformation, bone resorption, osteogenesis, and mineralization, providing a new paradigm for bone tissue engineering. This study reviews the classification of functionalized MOF composites in biomedicine and the application of their synthesis techniques in bone diseases. The unique in vivo and in vitro applications of MOFs in bone diseases, including osteoarthritis, osteoporosis, bone tumors, osteomyelitis, and periodontitis, are explored. Their properties include excellent drug loading and sustained release abilities, high antibacterial activity, and bone induction abilities. This review enables readers to better understand the cutting-edge progress of MOFs in bone regeneration applications, which is crucial for the design of and functional research on MOF-related nanomaterials. Full article