Acceleration of bone repairation by BMSCs overexpressing NGF combined with NSA and allograft bone scaffolds.

BACKGROUND: Repairation of bone defects remains a major clinical problem. Constructing bone tissue engineering containing growth factors, stem cells, and material scaffolds to repair bone defects has recently become a hot research topic. Nerve growth factor (NGF) can promote osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but the low survival rate of the BMSCs during transplantation remains an unresolved issue. In this study, we investigated the therapeutic effect of BMSCs overexpression of NGF on bone defect by inhibiting pyroptosis. METHODS: The relationship between the low survival rate and pyroptosis of BMSCs overexpressing NGF in localized inflammation of fractures was explored by detecting pyroptosis protein levels. Then, the NGF+/BMSCs-NSA-Sca bone tissue engineering was constructed by seeding BMSCs overexpressing NGF on the allograft bone scaffold and adding the pyroptosis inhibitor necrosulfonamide(NSA). The femoral condylar defect model in the Sprague-Dawley (SD) rat was studied by micro-CT, histological, WB and PCR analyses in vitro and in vivo to evaluate the regenerative effect of bone repair. RESULTS: The pyroptosis that occurs in BMSCs overexpressing NGF is associated with the nerve growth factor receptor (P75NTR) during osteogenic differentiation. Furthermore, NSA can block pyroptosis in BMSCs overexpression NGF. Notably, the analyses using the critical-size femoral condylar defect model indicated that the NGF+/BMSCs-NSA-Sca group inhibited pyroptosis significantly and had higher osteogenesis in defects. CONCLUSION: NGF+/BMSCs-NSA had strong osteogenic properties in repairing bone defects. Moreover, NGF+/BMSCs-NSA-Sca mixture developed in this study opens new horizons for developing novel tissue engineering constructs.

Prevention of bone dehiscence associated with orthodontic tooth movement by prophylactic injection of bone anabolic agents in mice.

Although bone dehiscence may occur during orthodontic tooth movement into the narrow alveolar ridge, a non-invasive prevention method is yet to be fully established. We show for the first time prevention of bone dehiscence associated with orthodontic tooth movement by prophylactic injection of bone anabolic agents in mice. In this study, we established a bone dehiscence mouse model by applying force application and used the granular type of scaffold materials encapsulated with bone morphogenetic protein (BMP)-2 and OP3-4, the receptor activator of NF-κB ligand (RANKL)-binding peptide, for the prophylactic injection to the alveolar bone. In vivo micro-computed tomography revealed bone dehiscence with decreased buccal alveolar bone thickness and height after force application, whereas no bone dehiscence was observed with the prophylactic injection after force application, and alveolar bone thickness and height were kept at similar levels as those in the control group. Bone histomorphometry analyses revealed that both bone formation and resorption parameters were significantly higher in the injection with force application group than in the force application without the prophylactic injection group. These findings suggest that the prophylactic local delivery of bone anabolic reagents can prevent bone dehiscence with increased bone remodelling activity.

Maxillary sinus lift augmentation: A randomized clinical trial with histological data comparing deproteinized bovine bone grafting vs graftless procedure with a 5-12-year follow-up.

INTRODUCTION: Different protocols and procedures for sinus lift and implant placement are available, generally involving the use of grafts to increase the tissue volume and/or prevent the Schneiderian membrane from collapsing. Among xenografts, deproteinised bovine bone graft (DBBP) is frequently used in sinus lift procedures. Leaving an ungrafted space following membrane elevation has proven to have a bony regenerative potential as well. This study aimed to compare the clinical and histological features of sinus lift surgery performed with or without biomaterials. METHODS: Patients with severe maxillary posterior atrophy (residual bone height 2-6 mm and residual crest thickness ≥4 mm), and in need of sinus lift surgery to allow the placement of three implants were enrolled and randomly divided into two groups. They underwent sinus lifts with DBBP (control) or with a graftless technique (test) and immediate placement of two implants (a mesial and distal one). After 6 months, a bone sample was retrieved from the area between the previously inserted fixtures, and a third, central implant was placed. The collected bone samples were analyzed morphologically and histomorphometrically. The patients were provided with prosthetic restorations after 6 months and followed up for 5-12 years. RESULTS: Ten patients were enrolled in the test and nine in the control group. The 6-month follow-up showed in the control group an average augmentation of 10.31 mm (±2.12), while in the test group it was 8.5 mm (±1.41) and a success rate of 96.3% in the control and 86.7% in the test group (p > 0.05). The histological analysis evidenced the presence of new bone tissue surrounded by immature osteoid matrix in the test group, and a variable number of DBBP particles surrounded by an immature woven bone matrix in the control group. CONCLUSION: The results of the present trial indicate that, with residual bone height of 2-6 mm and residual crest thickness ≥4 mm, sinus lift surgery with or without biomaterials followed by implant restoration, produces similar clinical and histological outcomes.

A Case of Endoscopic Partial Transverse Process and Sacral Alar Resection for Bertolotti's Syndrome and Continued Basketball Playing Two Years After Surgery.

Bertolotti's syndrome is a syndrome in which the transverse process of the most caudal lumbar vertebra becomes enlarged and articulates with the sacral alar, causing back pain. Here, we report a case of an adolescent basketball player with Bertolotti's syndrome who was unable to resume playing despite conservative treatment and underwent an endoscopic partial transverse process and sacral alar resection. A 16-year-old male basketball player presented to our hospital with a chief complaint of left low back pain during exercise and prolonged sitting for over one month. No obvious neurological abnormality was found. X-rays and CT showed lumbosacral transitional vertebrae, and the left transverse process of the sixth lumbar vertebra articulated with the sacrum and iliac, which was the Castellvi classification IIA. A block injection into the articulated surface produced improvement in pain, but the effect was not sustained. Since the patient was refractory to conservative treatments, such as medication and physiotherapy, surgery was performed. During surgery, the articulated transverse process and sacral alar were partially resected endoscopically. Because of the proximity of the resection site to the S1 nerve root, intraoperative electromyography (free-run EMG) was used to detect nerve root irritation symptoms in real time. The patient had no postoperative complications, his low back pain improved immediately, and he returned to play basketball three months after surgery. One year after surgery, the bone resection site showed gradual bone regeneration, and two years after surgery, the transverse process and sacral alar showed a bony bridge. The transverse process was enlarged compared to immediately after surgery but remained smaller than that before surgery. The patient continued to play basketball for two years after surgery without back pain, and no symptoms due to bone regeneration appeared. In the present case, a partial resection of the transverse process and sacral alar was performed with good results. Because the bone resection site was close to the S1 nerve root, the use of an endoscope and intraoperative free-run EMG allowed for a safer procedure during the bone resection. In addition, the patient did not present with symptoms that would affect his basketball performance, although the bone regenerated and bridging occurred between the transverse process and sacral alar over a two-year postoperative course.

Fish scale-derived hydroxyapatite for alveolar ridge preservation.

Alveolar ridge resorption following tooth extraction poses significant challenges for future dental restorations. This study investigated the efficacy of fish scale-derived hydroxyapatite (FSHA) as a socket preservation graft material to maintain alveolar bone volume and architecture. FSHA was extracted from *Labeo rohita* fish scales and characterized using Fourier transform infrared (FTIR) analysis. In vitro, biocompatibility and osteogenic potential were assessed using Saos-2 human osteosarcoma cells. Cell viability, migration, and proliferation were evaluated using MTT and scratch assays. In vivo performance was assessed in a rat model, and FSHA was compared to a commercial xenograft (Osseograft) and ungrafted controls. Histological analysis was performed at 8-week post-implantation to quantify new bone formation. FTIR confirmed the purity and homogeneity of FSHA. In vitro, FSHA enhanced Saos-2 viability, migration, and proliferation compared to controls. In vivo, FSHA demonstrated superior bone regeneration compared to Osseograft and ungrafted sites, with balanced graft resorption and new bone formation. Histological analysis revealed an active incorporation of FSHA into new bone, with minimal gaps and ongoing remodeling. Approximately 50%-60% of FSHA was resorbed by 8 weeks, closely matching the rate of new bone deposition. FSHA stimulated more bone formation in the apical socket region than in coronal areas. In conclusion, FSHA is a promising biomaterial for alveolar ridge preservation, exhibiting excellent biocompatibility, osteogenic potential, and balanced resorption. Its ability to promote robust bone regeneration highlights its potential as an effective alternative to currently used graft materials in socket preservation procedures.

The efficacy of Platelet and Leukocyte Rich Fibrin (L-PRF) in the healing process and bone repair in oral and maxillofacial surgeries: a systematic review.

INTRODUCTION: The search to optimize the healing and bone repair processes in oral and maxillofacial surgeries reflects the constant evolution in clinical practice, driven by the demand for increasingly satisfactory results and the need to minimize postoperative complications. OBJECTIVE: To evaluate the efficacy of Platelet and Leukocyte Rich Fibrin (L-PRF) in the healing and bone repair process in oral and maxillofacial surgeries. MATERIALS AND METHODS: The systematic review protocol for this study included the definition of the research question, the domain of the study, the databases searched, the search strategy, the inclusion and exclusion criteria, the types of studies to be included, the measures of effect, the methods for screening, data extraction and analysis, and the approach to data synthesis. Systematic literature searches were carried out on Cochrane databases, Web of Science, PubMed, ScienceDirect, Embase and Google Scholar. RESULTS: The strategic search in the databases identified 1,159 studies. After removing the duplicates with the Rayyan© software, 946 articles remained. Of these, 30 met the inclusion criteria. After careful evaluation based on the inclusion and exclusion criteria, 8 studies were considered highly relevant and included in the systematic review. CONCLUSION: Platelet and Leukocyte Rich Fibrin (L-PRF) has a positive effect on the healing process and bone repair in oral and maxillofacial surgeries.

Coaxial Electrospun Polycaprolactone/Gelatin Nanofiber Membrane Loaded with Salidroside and Cryptotanshinone Synergistically Promotes Vascularization and Osteogenesis.

Background: Salidroside (SAL) is the most effective component of Rhodiola rosea, a traditional Chinese medicine. Cryptotanshinone (CT) is the main fat-soluble extract of Salvia miltiorrhiza, exhibiting considerable potential for application in osteogenesis. Herein, a polycaprolactone/gelatin nanofiber membrane loaded with CT and SAL (PSGC membrane) was successfully fabricated via coaxial electrospinning and characterized. Methods and Results: This membrane capable of sustained and controlled drug release was employed in this study. Co-culturing the membrane with bone marrow mesenchymal stem cells and human umbilical vein endothelial cells revealed excellent biocompatibility and demonstrated osteogenic and angiogenic capabilities. Furthermore, drug release from the PSGC membrane activated the Wnt/ß-catenin signaling pathway and promoted osteogenic differentiation and vascularization. Evaluation of the membrane's vascularization and osteogenic capacities involved transplantation onto a rat's subcutaneous area and assessing rat cranium defects for bone regeneration, respectively. Microcomputed tomography, histological tests, immunohistochemistry, and immunofluorescence staining confirmed the membrane's outstanding angiogenic capacity two weeks post-operation, with a higher incidence of osteogenesis observed in rat cranial defects eight weeks post-surgery. Conclusion: Overall, the SAL- and CT-loaded coaxial electrospun nanofiber membrane synergistically enhances bone repair and regeneration.

Surgical Management of Radicular Cyst With the Use of Advanced Platelet-Rich Fibrin and Bone Graft: A Case Report.

In addition to helping with wound healing, periapical surgery is performed to remove periapical disease. Concentrates of platelets have been applied extensively in endodontics and other fields of regenerative medicine. A periapical inflammatory lesion was found in a 35-year-old male patient who complained of pain in the maxillary anterior region and displayed slight edema in the same area. The lesion was treated with periapical surgery utilizing advanced platelet-rich fibrin (A-PRF). Mesenchymal stem cell processes of proliferation and differentiation can be induced by several types of platelet concentrates. Growth factors are released at the application site by platelet-rich fibrin (PRF) for a minimum of seven days. The activity of osteoblasts is stimulated by growth factors and secreted cytokines. Furthermore, the release of growth factors promotes fibroblast migration, which quickens tissue regeneration.  In addition to helping with wound healing, periapical surgery is performed to remove periapical disease. The synthesis of fibrin networks laden with platelets and growth factors is made possible by PRF, which is subsequently used to accelerate bone regeneration and, consequently, to improve bone formation. In this instance, the best possible bone regeneration and repair were accomplished. After 12 weeks, 24 weeks, and 36 weeks, the patient was brought back for follow-ups. He was found to be asymptomatic, and the radiograph showed considerable periapical healing with nearly enough bone production.

Photobiomodulation and mesenchymal stem cell-conditioned medium for the repair of experimental critical-size defects.

Orthopedic surgeons face a significant challenge in treating critical-size femoral defects (CSFD) caused by osteoporosis (OP), trauma, infection, or bone tumor resections. In this study for the first time, the application of photobiomodulation (PBM) and bone marrow mesenchymal stem cell-conditioned medium (BM-MSC-CM) to improve the osteogenic characteristics of mineralized bone scaffold (MBS) in ovariectomy-induced osteoporotic (OVX) rats with a CSFD was tested. Five groups of OVX rats with CSFD were created: (1) Control (C); (2) MBS; (3) MBS + CM; (4) MBS + PBM; (5) MBS + CM + PBM. Computed tomography scans (CT scans), compression indentation tests, and histological and stereological analyses were carried out after euthanasia at 12 weeks following implantation surgery. The CT scan results showed that CSFD in the MBS + CM, MBS + PBM, and MBS + CM + PBM groups was significantly smaller compared to the control group (p = 0.01, p = 0.04, and p = 0.000, respectively). Moreover, the CSFD size was substantially smaller in the MBS + CM + PBM treatment group than in the MBS, MBS + CM, and MBS + PBM treatment groups (p = 0.004, p = 0.04, and p = 0.01, respectively). The MBS + PBM and MBS + CM + PBM treatments had significantly increased maximum force relative to the control group (p = 0.01 and p = 0.03, respectively). Bending stiffness significantly increased in MBS (p = 0.006), MBS + CM, MBS + PBM, and MBS + CM + PBM treatments (all p = 0.004) relative to the control group. All treatment groups had considerably higher new trabecular bone volume (NTBV) than the control group (all, p = 0.004). Combined therapies with MBS + PBM and MBS + CM + PBM substantially increased the NTBV relative to the MBS group (all, p = 0.004). The MBS + CM + PBM treatment had a markedly higher NTBV than the MBS + PBM (p = 0.006) and MBS + CM (p = 0.004) treatments. MBS + CM + PBM, MBS + PBM, and MBS + CM treatments significantly accelerated bone regeneration of CSFD in OVX rats. PBM + CM enhanced the osteogenesis of the MBS compared to other treatment groups.

A strip free gingival graft and a xenogeneic collagen matrix to increase keratinized tissue after vertical bone augmentation.

PURPOSE: After vertical bone augmentation (VBA) surgery, loss of both keratinized tissue (KT) and vestibule depth (VD) take place. This article evaluated KT gain, patient satisfaction, and aesthetic outcomes after a modified apically repositioned flap (ARF) in combination with a strip-free gingival graft (FGG) harvested from the palate and a xenogeneic collagen matrix (XCM) to correct mucogingival distortion (MGD) after VBA. This technique minimizes patient morbidity by reducing the need for extensive masticatory mucosa grafts. MATERIALS: The study included 12 patients with ≤3 mm KT after vertical augmentation procedures. KT gain and tissue thickness were measured. Patient morbidity and aesthetic outcomes were also evaluated. RESULTS: Twenty-four months after surgery, significant VD gain was observed, obtaining a vertical KT augmentation of 5.38 ± 2.06 mm, although tissue thickness increase was only 0.42 ± 0.42mm. Regarding patient satisfaction, aesthetic results evaluating tissue color and texture were satisfactory; the pain was slight, obtaining a score of 2.10 ± 1.13 out of 10, measured using a Visual Analogue Scale (VAS). CONCLUSION: The present retrospective case series study shows that using an apically repositioned flap combined with a strip FGG and an XCM might offer a valid means of achieving KT gain.

Potentiating effect of AMD3100 on bone morphogenetic protein-2 induced bone regeneration.

BACKGROUND: AMD3100, a CXCR4 antagonist, is currently prescribed for activating the mobilization of hematopoietic stem cells. Recently, AMD3100 was shown to potentiate bone morphogenetic protein-2 (BMP-2)-induced bone formation by stimulating the trafficking of mesenchymal cells. However, optimization of the strategic combination of AMD3100 and BMP-2 has not yet been clearly established. The purpose of this study was to evaluate the effect of AMD3100 on BMP-2-induced bone regeneration in vitro and in a mouse calvarial defect healing model. METHODS: In vitro osteoblastic differentiation and cell migration after sequential treatments with AMD3100 and BMP-2 were analyzed by alkaline phosphatase (ALP) activity, ALP staining, and calcium accumulation. Migration capacity was evaluated after treating mesenchymal cells with AMD3100 and/or BMP-2. A critical-size calvarial defect model was used to evaluate bone formation after sequential or continuous treatment with AMD3100 and BMP-2. The degree of bone formation in the defect was analyzed using micro-computed tomography (micro-CT) and histological staining. RESULTS: Compared with single treatment using either AMD3100 or BMP-2 alone, sequential treatment with AMD3100 followed by BMP-2 on mesenchymal cells increased osteogenic differentiation. Application of AMD3100 and subsequent BMP-2 significantly activated cell migration on mesenchymal cell than BMP-2 alone or AMD3100 alone. Micro-CT and histomorphometric analysis showed that continuous intraperitoneal (IP) injection of AMD3100 resulted significantly increased new bone formation in BMP-2 loaded scaffold in calvarial defect than control groups without AMD3100 IP injection. Additionally, both single IP injection of AMD3100 and subsequent BMP-2 injection to the scaffold in calvarial defect showed pronounced new bone formation compared to continuous BMP-2 treatment without AMD3100 treatment. CONCLUSION: Our data suggest that single or continuous injection of AMD3100 can potentiate BMP-2-induced osteoblastic differentiation and bone regeneration. This strategic combination of AMD3100 and BMP-2 may be a promising therapy for bone regeneration.

Impact of Resolvin-E1 and Maresin-1 on Bone Marrow Stem Cell Osteogenesis under Inflammatory Stress.

Periodontal disease is characterized by inflammation and bone loss. Central to its pathogenesis is the dysregulated inflammatory response, complicating regenerative therapies. Mesenchymal stem cells (MSCs) hold significant promise in tissue repair and regeneration. This study investigated the effects of specialized pro-resolving mediators (SPMs), Resolvin E1 (RvE1) and Maresin 1 (MaR1), on the osteogenic differentiation of human bone marrow-derived MSCs under inflammatory conditions. The stem cells were treated with SPMs in the presence of lipopolysaccharide (LPS) to simulate an inflammatory environment. Osteogenic differentiation was assessed through alkaline phosphatase activity and alizarin red staining. Proteomic analysis was conducted to characterize the protein expression profile changes, focusing on proteins related to osteogenesis and osteoclastogenesis. Treatment with RvE1 and MaR1, both individually and in combination, significantly enhanced calcified deposit formation. Proteomic analysis revealed the differential expression of proteins associated with osteogenesis and osteoclastogenesis, highlighting the modulatory impact of SPMs on bone metabolism. RvE1 and MaR1 promote osteogenic differentiation of hBMMSCs in an inflammatory environment, with their combined application yielding synergistic effects. This study provides insights into the therapeutic potential of SPMs in enhancing bone regeneration, suggesting a promising avenue for developing regenerative therapies for periodontal disease and other conditions characterized by inflammation-induced bone loss.

Pioneering nanomedicine in orthopedic treatment care: a review of current research and practices.

A developing use of nanotechnology in medicine involves using nanoparticles to administer drugs, genes, biologicals, or other materials to targeted cell types, such as cancer cells. In healthcare, nanotechnology has brought about revolutionary changes in the treatment of various medical and surgical conditions, including in orthopedic. Its clinical applications in surgery range from developing surgical instruments and suture materials to enhancing imaging techniques, targeted drug delivery, visualization methods, and wound healing procedures. Notably, nanotechnology plays a significant role in preventing, diagnosing, and treating orthopedic disorders, which is crucial for patients' functional rehabilitation. The integration of nanotechnology improves standards of patient care, fuels research endeavors, facilitates clinical trials, and eventually improves the patient's quality of life. Looking ahead, nanotechnology holds promise for achieving sustained success in numerous surgical disciplines, including orthopedic surgery, in the years to come. This review aims to focus on the application of nanotechnology in orthopedic surgery, highlighting the recent development and future perspective to bridge the bridge for clinical translation.

Emerging materials and technologies for advancing bioresorbable surgical meshes.

Surgical meshes play a significant role in the treatment of various medical conditions, such as hernias, pelvic floor issues, guided bone regeneration, and wound healing. To date, commercial surgical meshes are typically made of non-absorbable synthetic polymers, notably polypropylene and polytetrafluoroethylene, which are associated with postoperative complications, such as infections. Biological meshes, based on native tissues, have been employed to overcome such complications, though mechanical strength has been a main disadvantage. The right balance in mechanical and biological performances has been achieved by the advent of bioresorbable meshes. Despite improvements, recurrence of clinical complications associated with surgical meshes raises significant concerns regarding the technical adequacy of current materials and designs, pointing to a crucial need for further development. To this end, current research focuses on the design of meshes capable of biomimicking native tissue and facilitating the healing process without post-operative complications. Researchers are actively investigating advanced bioresorbable materials, both synthetic polymers and natural biopolymers, while also exploring the performance of therapeutic agents, surface modification methods and advanced manufacturing technologies such as 4D printing. This review seeks to evaluate emerging biomaterials and technologies for enhancing the performance and clinical applicability of the next-generation surgical meshes. STATEMENT OF SIGNIFICANCE: In the ever-transforming landscape of regenerative medicine, the embracing of engineered bioabsorbable surgical meshes stands as a key milestone in addressing persistent challenges and complications associated with existing treatments. The urgency to move beyond conventional non-absorbable meshes, fraught with post-surgery complications, emphasises the necessity of using advanced biomaterials for engineered tissue regeneration. This review critically examines the growing field of absorbable surgical meshes, considering their potential to transform clinical practice. By strategically combining mechanical strength with bioresorbable characteristics, these innovative meshes hold the promise of mitigating complications and improving patient outcomes across diverse medical applications. As we navigate the complexities of modern medicine, this exploration of engineered absorbable meshes emerges as a promising approach, offering an overall perspective on biomaterials, technologies, and strategies adopted to redefine the future of surgical meshes.

Exploring the biocompatibility and healing activity of actinobacterial-enhanced reduced nano-graphene oxide in in vitro and in vivo model and induce bone regeneration through modulation of OPG/RANKL/RUNX2/ALP pathways.

BACKGROUND: The development of cost-effective, simple, environment-friendly biographene is an area of interest. To accomplish environmentally safe, benign culturing that has advantages over other methods to reduce the graphene oxide (GO), extracellular metabolites from actinobacteria associated with mushrooms were used for the first time. METHODS: Bactericidal effect of GO against methicillin-resistant Staphylococcus aureus, antioxidant activity, and hydroxyapatite-like bone layer formation, gene expression analysis and appropriate biodegradation of the microbe-mediated synthesis of graphene was studied. RESULTS: Isolated extracellular contents Streptomyces achromogenes sub sp rubradiris reduced nano-GO to graphene (rGO), which was further examined by spectrometry and suggested an efficient conversion and significant reduction in the intensity of all oxygen-containing moieties and shifted crystalline peaks. Electron microscopic results also suggested the reduction of GO layer. In addition, absence of significant toxicity in MG-63 cell line, intentional free radical scavenging prowess, liver and kidney histopathology, and Wistar rat bone regeneration through modulation of OPG/RANKL/RUNX2/ALP pathways show the feasibility of the prepared nano GO. CONCLUSIONS: The study demonstrates the successful synthesis of biographene from actinobacterial extracellular metabolites, its potential biomedical applications, and its promising role in addressing health and environmental concerns.

Successful treatment of nasopalatine duct cyst after maxillary anterior implant surgery: a case report.

BACKGROUND: Sporadic studies have reported the occurrence of nasopalatine duct cysts after maxillary anterior implant surgery, and the treatment methods still have clinical uncertainty. PURPOSE: We report a potential therapy method that successfully treated a nasopalatine duct cyst that developed and expanded one year after maxillary anterior implant placement following periodontally hopeless teeth extraction. MATERIALS AND METHODS: The nasopalatine cyst was treated surgically without removing implants. During flap surgery, the cyst was removed intact, and the exposed implant's surface was debrided thoroughly by hydrogen peroxide (H2O2) rinsing, glycine air polishing, and saline rinsing. To deal with the significant bone defect caused by the cyst, a bovine porous bone mineral injected platelet-rich fibrin (BPBM-i-PRF) complex was applied to fill the defect, following a resorbable collagen membrane to cover. RESULTS: 7 years after surgery, no cyst recurrence was observed, and bone regeneration in the bone graft area was stable. The implants functioned well without mobility. CONCLUSIONS: For nasopalatine duct cysts associated with dental implant placement, complete surgical debridement and longitudinal stable bone regeneration are possibly accessible by regenerative surgery without implant removal.

Translational Experimental Basis of Indirect Adenosine Receptor Agonist Stimulation for Bone Regeneration: A Review.

Bone regeneration remains a significant clinical challenge, often necessitating surgical approaches when healing bone defects and fracture nonunions. Within this context, the modulation of adenosine signaling pathways has emerged as a promising therapeutic option, encouraging osteoblast activation and tempering osteoclast differentiation. A literature review of the PubMed database with relevant keywords was conducted. The search criteria involved in vitro or in vivo models, with clear methodological descriptions. Only studies that included the use of indirect adenosine agonists, looking at the effects of bone regeneration, were considered relevant according to the eligibility criteria. A total of 29 articles were identified which met the inclusion and exclusion criteria, and they were reviewed to highlight the preclinical translation of adenosine agonists. While preclinical studies demonstrate the therapeutic potential of adenosine signaling in bone regeneration, its clinical application remains unrealized, underscoring the need for further clinical trials. To date, only large, preclinical animal models using indirect adenosine agonists have been successful in stimulating bone regeneration. The adenosine receptors (A1, A2A, A2B, and A3) stimulate various pathways, inducing different cellular responses. Specifically, indirect adenosine agonists act to increase the extracellular concentration of adenosine, subsequently agonizing the respective adenosine receptors. The agonism of each receptor is dependent on its expression on the cell surface, the extracellular concentration of adenosine, and its affinity for adenosine. This comprehensive review analyzed the multitude of indirect agonists currently being studied preclinically for bone regeneration, discussing the mechanisms of each agonist, their cellular responses in vitro, and their effects on bone formation in vivo.

Role of Adipose-Derived Mesenchymal Stem Cells in Bone Regeneration.

Bone regeneration involves multiple factors such as tissue interactions, an inflammatory response, and vessel formation. In the event of diseases, old age, lifestyle, or trauma, bone regeneration can be impaired which could result in a prolonged healing duration or requiring an external intervention for repair. Currently, bone grafts hold the golden standard for bone regeneration. However, several limitations hinder its clinical applications, e.g., donor site morbidity, an insufficient tissue volume, and uncertain post-operative outcomes. Bone tissue engineering, involving stem cells seeded onto scaffolds, has thus been a promising treatment alternative for bone regeneration. Adipose-derived mesenchymal stem cells (AD-MSCs) are known to hold therapeutic value for the treatment of various clinical conditions and have displayed feasibility and significant effectiveness due to their ease of isolation, non-invasive, abundance in quantity, and osteogenic capacity. Notably, in vitro studies showed AD-MSCs holding a high proliferation capacity, multi-differentiation potential through the release of a variety of factors, and extracellular vesicles, allowing them to repair damaged tissues. In vivo and clinical studies showed AD-MSCs favoring better vascularization and the integration of the scaffolds, while the presence of scaffolds has enhanced the osteogenesis potential of AD-MSCs, thus yielding optimal bone formation outcomes. Effective bone regeneration requires the interplay of both AD-MSCs and scaffolds (material, pore size) to improve the osteogenic and vasculogenic capacity. This review presents the advances and applications of AD-MSCs for bone regeneration and bone tissue engineering, focusing on the in vitro, in vivo, and clinical studies involving AD-MSCs for bone tissue engineering.

Harnessing extracellular vesicles-mediated signaling for enhanced bone regeneration: novel insights into scaffold design.

The increasing prevalence of bone replacements and complications associated with bone replacement procedures underscores the need for innovative tissue restoration approaches. Existing synthetic grafts cannot fully replicate bone vascularization and mechanical characteristics. This study introduces a novel strategy utilizing pectin, chitosan, and polyvinyl alcohol to create interpenetrating polymeric network (IPN) scaffolds incorporated with extracellular vesicles (EVs) isolated from human mesenchymal stem cells (hMSCs). We assess the osteointegration and osteoconduction abilities of these modelsin vitrousing hMSCs and MG-63 osteosarcoma cells. Additionally, we confirm exosome properties through Transmission Electron Microscopy (TEM), immunoblotting, and Dynamic Light Scattering (DLS).In vivo, chick allantoic membrane assay investigates vascularization characteristics. The study did not includein vivoanimal experiments. Our results demonstrate that the IPN scaffold is highly porous and interconnected, potentially suitable for bone implants. EVs, approximately 100 nm in size, enhance cell survival, proliferation, alkaline phosphatase activity, and the expression of osteogenic genes. EVs-mediated IPN scaffolds demonstrate promise as precise drug carriers, enabling customized treatments for bone-related conditions and regeneration efforts. Therefore, the EVs-mediated IPN scaffolds demonstrate promise as precise carriers for the transport of drugs, allowing for customized treatments for conditions connected to bone and efforts in regeneration.

Lithium Promotes Osteogenesis via Rab11a-Facilitated Exosomal Wnt10a Secretion and ß-Catenin Signaling Activation.

Both bone mesenchymal stem cells (BMSCs) and their exosomes suggest promising therapeutic tools for bone regeneration. Lithium has been reported to regulate BMSC function and engineer exosomes to improve bone regeneration in patients with glucocorticoid-induced osteonecrosis of the femoral head. However, the mechanisms by which lithium promotes osteogenesis have not been elucidated. Here, we demonstrated that lithium promotes the osteogenesis of BMSCs via lithium-induced increases in the secretion of exosomal Wnt10a to activate Wnt/ß-catenin signaling, whose secretion is correlated with enhanced MARK2 activation to increase the trafficking of the Rab11a and Rab11FIP1 complexes together with exosomal Wnt10a to the plasma membrane. Then, we compared the proosteogenic effects of exosomes derived from lithium-treated or untreated BMSCs (Li-Exo or Con-Exo) both in vitro and in vivo. We found that, compared with Con-Exo, Li-Exo had superior abilities to promote the uptake and osteogenic differentiation of BMSCs. To optimize the in vivo application of these hydrogels, we fabricated Li-Exo-functionalized gelatin methacrylate (GelMA) hydrogels, which are more effective at promoting osteogenesis and bone repair than Con-Exo. Collectively, these findings demonstrate the mechanism by which lithium promotes osteogenesis and the great promise of lithium for engineering BMSCs and their exosomes for bone regeneration, warranting further exploration in clinical practice.