Lactate promotes bone healing by regulating the osteogenesis of bone marrow mesenchymal stem cells through activating Olfr1440.

Bone malunion or nonunion leads to functional and esthetic problems and is a major healthcare burden. Activation of bone marrow mesenchymal stem cells (BMSCs) and subsequent induction of osteogenic differentiation by local metabolites are crucial steps for bone healing, which has not yet been completely investigated. Here, we found that lactate levels are rapidly increased at the local injury site during the early phase of bone defect healing, which facilitates the healing process by enhancing BMSCs regenerative capacity. Mechanistically, lactate serves as a ligand for the Olfr1440 olfactory receptor, to trigger an intracellular calcium influx that in turn activates osteogenic phenotype transition of BMSCs. Conversely, ablation of Olfr1440 delays skeletal repair and remodelling, as evidenced by thinner cortical bone and less woven bone formation in vivo. Administration of lactate in the defect area enhanced bone regeneration. These findings thus revealed the key roles of lactate in the osteogenic differentiation of BMSCs, which deepened our understanding of the bone healing process, as well as provided cues for a potential therapeutic option that might greatly improve bone defect treatment.

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.

Glycinamide Facilitates Nanocomplex Formation and Functions Synergistically with Bone Morphogenetic Protein 2 to Promote Osteoblast Differentiation In Vitro and Bone Regeneration in a Mouse Calvarial Defect Model.

BACKGROUND: This study aimed to identify glycine analogs conducive to the formation of cell-absorbable nanocomplexes, enhancing collagen synthesis and subsequent osteogenesis in combination with BMP2 for improved bone regeneration. METHODS: Glycine and its derivatives were assessed for their effects on osteogenic differentiation in MC3T3-E1 cells and human bone marrow mesenchymal stem cells (BMSCs) under osteogenic conditions or with BMP2. Osteogenic differentiation was assessed through alkaline phosphatase staining and real-time quantitative polymerase chain reaction (RT-qPCR). Nanocomplex formation was examined via scanning electron microscopy, circular dichroism, and ultraviolet-visible spectroscopy. In vivo osteogenic effects were validated using a mouse calvarial defect model, and bone regeneration was evaluated through micro-computed tomography and histomorphometric analysis. RESULTS: Glycine, glycine methyl ester, and glycinamide significantly enhanced collagen synthesis and ALP activity in conjunction with an osteogenic medium (OSM). GA emerged as the most effective inducer of osteoblast differentiation marker genes. Combining GA with BMP2 synergistically stimulated ALP activity and the expression of osteoblast markers in both cell lines. GA readily formed nanocomplexes, facilitating cellular uptake through strong electrostatic interactions. In an in vivo calvarial defect mouse model, the GA and BMP2 combination demonstrated enhanced bone volume, bone volume/tissue volume ratio, trabecular numbers, and mature bone formation compared to other combinations. CONCLUSION: GA and BMP2 synergistically promoted in vitro osteoblast differentiation and in vivo bone regeneration through nanocomplex formation. This combination holds therapeutic promise for individuals with bone defects, showcasing its potential for clinical intervention.

Fullerol-reinforced antioxidantive 3D-printed bredigite scaffold for accelerating bone healing.

Reactive oxygen species play a vital role in tissue repair, and nonequilibrium of redox homeostasis around bone defect can compromise osteogenesis. However, insufficient antioxidant capacity and weak osteogenic performance remain major obstacles for bone scaffold materials. Herein, integrating the mussel-inspired polydopamine (PDA) coating and 3D printing technologies, we utilized the merits of both osteogenic bredigite and antioxidative fullerol to construct 3D-printed porous, biodegradable acid-buffering, reactive oxygen species (ROS) -scavenging and robust osteogenic bio-scaffold (denoted "FPBS") for in situ bone defect restoration under oxidative stress microenvironment. Initially, fullerol nanoparticles were attached to the surface of the bredigite scaffold via covalently inter-crosslinking with PDA. Upon injury, extracellular ROS capturing triggered the oxidative degradation of PDA, releasing fullerol nanoparticles to enter into cells for further intracellular ROS scavenging. In vitro, FPBS had good biocompatibility and excellent antioxidative capability. Furthermore, FPBS promoted the osteogenesis of stem cells with significant elevation of osteogenic markers. Finally, in vivo implantation of FPBS remarkably enhanced new bone formation in a rat critical calvarial defect model. Overall, with amelioration of the ROS microenvironment of injured tissue and enhancement of osteogenic differentiation of stem cells simultaneously, FPBS may hold great potential towards bone defect repair.

Adhesion of Candida albicans on PTFE membranes used in guided bone regeneration.

OBJECTIVES: Guided bone regeneration (GBR) is a core procedure used to regenerate bone defects. The aim of the study was to investigate the adherence of Candida albicans on six commercially available polytetrafluoroethylene (PTFE) membranes used in GBR procedures and the subsequent clinical consequences. MATERIALS AND METHODS: Six commercially available PTFE membranes were tested. Two of the membranes had a textured surface and the other four a plane, nontextured one. C. albicans (ATCC 24433) was cultured for 24 h, and its cell surface hydrophobicity was assessed using a modified method. C. albicans adhesion to membrane discs was studied by scanning electron microscopy (SEM) and real-time polymerase chain reaction (PCR). RESULTS: C. albicans was found to be hydrophobic (77.25%). SEM analysis showed that C. albicans adherence to all membranes examined was characterized by patchy, scattered, and small clustered patterns except for one nontextured membrane with a most rough surface in which a thick biofilm was observed. Real-time PCR quantification revealed significantly greater adhesion of C. albicans cells to PTFE membranes than the control membrane (p ≤ .001) with the membranes having a textured surface exhibiting the highest count of 2680 × 104 cells/ml compared to the count of 707 × 104 cells/mL on those with a nontextured one (p ≤ .001). One membrane with nontextured surface, but with most rough surface was found to exhibit the highest count of 3010 × 104 cells/ml (p ≤ .05). CONCLUSION: The results of this study indicate that C. albicans adhesion on membranes' surfaces depends on the degree of surface roughness and/or on the presence of a texture. Textured PTFE membranes and/or membranes high roughness showed significantly more adhered C. albicans cells. These findings can impact the surgeon's choice of GBR membrane and postoperative maintenance.

An injectable and coagulation-independent Tetra-PEG hydrogel bioadhesive for post-extraction hemostasis and alveolar bone regeneration.

Effective control of post-extraction hemorrhage and alveolar bone resorption is critical for successful extraction socket treatment, which remains an unmet clinical challenge. Herein, an injectable Tetra-PEG hydrogel that possesses rapid gelation, firm tissue adhesion, high mechanical strength, suitable degradability, and excellent biocompatibility is developed as a sutureless and coagulation-independent bioadhesive for the management of extraction sockets. Our results demonstrate that the rapid and robust adhesive sealing of the extraction socket by the Tetra-PEG hydrogel can provide reliable protection for the underlying wound and stabilize blood clots to facilitate tissue healing. In vivo experiments using an anticoagulated rat tooth extraction model show that the hydrogel significantly outperformed clinically used cotton and gelatin sponge in hemostatic efficacy, wound closure, alveolar ridge preservation, and in situ alveolar bone regeneration. Histomorphological evaluations reveal the mechanisms for accelerated bone repair through suppressed long-term inflammation, elevated collagen deposition, higher osteoblast activity, and enhanced angiogenesis. Together, our study highlights the clinical potential of the developed injectable Tetra-PEG hydrogel for treating anticoagulant-related post-extraction hemorrhage and improving socket healing.

MXene reinforced microporous bacterial cellulose/sodium alginate dual crosslinked cryogel for bone tissue engineering.

The entangled assembly of bacterial cellulose (BC) nanofibers does not provide a three-dimensional (3D) macroporous structure for cellular infiltration thus hindering its use as a scaffold for bone tissue engineering. In addition, it is difficult to achieve uniform dispersion of bioactive agents in entangled BC nanofibers. To address this, the BC nanofibers were integrated with MXene, a two-dimensional nanomaterial known for its electrical signaling and mechanical strength, along with sodium alginate to form cryogel. The cryogel was fabricated using a cross-linking to enhance its mechanical properties, pores for cellular infilteration. MXene incorporation not only increased water absorption (852% to 1446%) and retention (692% to 973%) ability but also significantly improved the compressive stress (0.85 MPa to 1.43 MPa) and modulus (0.22 MPa to 1.17 MPa) confirming successful MXene reinforcement in cryogel. Biological evaluation revealed that the optimum concentration of MXene increased the cell proliferation and the osteogenic role of fabricated scaffolds was also confirmed through osteogenic gene expressions. The macropores in reconstructed MXene-BC-based cryogel provided ample space for cellular proliferation. The osteogenic role of the scaffold was examined through various gene expressions. The Quantitative polymerase chain reaction (QTPCR) revealed that MXene-loaded scaffolds especially in low concentration, had an obvious osteogenic effect hence concluding that BC can not only be reconstructed into the desired form but osteogenic property can be induced. These findings can open a new way of reconstructing BC into a more optimal structure to overcome its structural limitations and retain its natural bioactivities.

Advancing Bioactive Material for Mandibular Bone Regeneration: Transformation of Fibrous Mat into 3D Matrix Cotton for Enhanced Shape Retention and Rapid Hemostasis.

Transformation of a fibrous mat into a three-dimensional (3D) scaffold opens up abundant innovative prospects in biomedical research, particularly for studying both soft as well as hard tissues. Electrospun nanofibers, which mimic the extracellular matrix have attracted significant attention in various studies. This research focuses on rapidly converting a fibrous mat made of polycaprolactone (PCL)/pluronic F-127 (PF-127) with different percentages of monetite calcium phosphate (MCP) into desirable 3D matrix cotton using a unique gas foaming technology. These matrix cottons possess biomimetic properties and have oriented porous structures. Using this innovative technique, various shapes of 3D matrix cotton, such as squares, hollow tubes, and other customizable forms, were successfully produced. Importantly, these 3D matrix cottons showed a consistent distribution of monetite particles with total porosity ranging from 90% to 98%. The structure of the 3D matrix cotton, its water/blood absorption capacity, the potential for causing non-hemolysis, and rapid hemostatic properties were thoroughly investigated. Additionally, periodontal cells were cultured on the 3D matrix cotton to assess their viability and morphology, revealing promising results. Furthermore, a coculture study involving NIH-3T3 and MG-63 cells on the 3D matrix cotton showed spheroidal formation within 24 h. Notably, in vitro assessments indicated that the matrix cotton containing 15% monetite (PCL-MMC15%) exhibited superior absorbent capabilities, excellent cell viability, and rapid hemostatic characteristics. Subsequently, the effectiveness of PCL-MMC15% in promoting mandibular bone regeneration was evaluated through an in vivo study on rabbits using a mandibular injury model. The results demonstrated that PCL-MMC15% facilitated the resolution of defects in the mandibular region by initiating new bone formation. Therefore, the presented 3D matrix cotton (PCL-MMC15%) shows significant promise for applications in both mandibular bone regeneration and hemostasis.

The role of bone ring technique for bone augmentation in implant surgery: A Narrative Review.

Bone grafting with simultaneous implant placement using the novel bone ring technique was a procedure introduced with the intention of three-dimensional bone augmentation with simultaneous implant placement in both maxilla and mandible. A ring-shaped bone is placed in the socket, which is secured by an implant placed through the ring. The current narrative review was planned to provide a concise summary of the core concepts surrounding bone augmentation, to provide context for understanding the bone ring technique, and to highlight the basics of bone grafting and the origin of the technique to its advancement and its importance in the light of current literature.

Nanofibrous Microspheres: A Biomimetic Platform for Bone Tissue Regeneration.

Bone, a fundamental constituent of the human body, is a vital scaffold for support, protection, and locomotion, underscoring its pivotal role in maintaining skeletal integrity and overall functionality. However, factors such as trauma, disease, or aging can compromise bone structure, necessitating effective strategies for regeneration. Traditional approaches often lack biomimetic environments conducive to efficient tissue repair. Nanofibrous microspheres (NFMS) present a promising biomimetic platform for bone regeneration by mimicking the native extracellular matrix architecture. Through optimized fabrication techniques and the incorporation of active biomolecular components, NFMS can precisely replicate the nanostructure and biochemical cues essential for osteogenesis promotion. Furthermore, NFMS exhibit versatile properties, including tunable morphology, mechanical strength, and controlled release kinetics, augmenting their suitability for tailored bone tissue engineering applications. NFMS enhance cell recruitment, attachment, and proliferation, while promoting osteogenic differentiation and mineralization, thereby accelerating bone healing. This review highlights the pivotal role of NFMS in bone tissue engineering, elucidating their design principles and key attributes. By examining recent preclinical applications, we assess their current clinical status and discuss critical considerations for potential clinical translation. This review offers crucial insights for researchers at the intersection of biomaterials and tissue engineering, highlighting developments in this expanding field.

Bioactive material­sodium alginate-polyvinyl alcohol composite film scaffold for bone tissue engineering application.

Road accidents and infection-causing diseases during bone surgery are serious problems in orthopedics, and thus, addressing these pressing challenges is crucial. In the present study, the 70S30C calcium silicate bioactive material (BM) is synthesized by a sustainable approach employing a precipitation method using recycled rice husk and eggshells as a precursor of silica and calcium. Further, 70S30C BM is composited with sodium alginate (SA) and polyvinyl alcohol (PVA), and the films were prepared by solvent casting method. The composite films were prepared without the addition of acid, binder, and crosslinking agents. Further, the films were characterized by BET, XRD, ATR-FTIR, SEM, and EDS mapping. The in vitro bioactivity and biodegradation study is performed in the simulated body fluid (SBF). The in vitro haemolysis study is executed using human blood and the results demonstrate haemocompatibility of the composite films. The ex ovo CAM assay also exhibits good neovascularization. The in vitro and in vivo biocompatibility assay proves its non-toxic nature. Further, the in vivo study reveals that the engineered composite film demonstrates accelerated osteogenesis. This work broadens the orthopedic potential of the composite film and offers bioactivity, haemocompatibility, angiogenesis, non-toxicity, and in vivo osteogenesis which would serve as a potential candidate for bone tissue engineering application.

Contribution of initial lymphatics to oral wound healing after tooth extraction.

Lymphatics are involved in the resolution of inflammation and wound healing, but their role in the oral wound healing process after tooth extraction has never been investigated. We therefore sought to evaluate the healing process following the extraction of maxillary molars in two transgenic mouse models: K14-VEGFR3-Ig mice, which lack initial mucosal lymphatic vessels, and K14-VEGFC mice, which have hyperplastic mucosal lymphatics. Maxillary molars were extracted from both transgenic mouse types and their corresponding wild-type (WT) controls. Mucosal and alveolar bone healing were evaluated. A delayed epithelialization and bone regeneration were observed in K14-VEGFR3-Ig mice compared with their WT littermates. The hampered wound closure was accompanied by decreased levels of epidermal growth factor (EGF) and persistent inflammation, characterized by infiltrates of immune cells and elevated levels of pro-inflammatory markers in the wounds. Hyperplastic mucosal lymphatics did not enhance the healing process after tooth extraction in K14-VEGFC mice. The findings indicate that initial mucosal lymphatics play a major role in the initial phase of the oral wound healing process.

Antibacterial and Osteogenic Dual-Functional Micronano Composite Scaffold Fabricated via Melt Electrowriting and Solution Electrospinning for Bone Tissue Engineering.

The utilization of micronano composite scaffolds has been extensively demonstrated to confer the superior advantages in bone repair compared to single nano- or micron-sized scaffolds. Nevertheless, the enhancement of bioactivities within these composite scaffolds remains challenging. In this study, we propose a novel approach to combine melt electrowriting (MEW) and solution electrospinning (SES) techniques for the fabrication of a composite scaffold incorporating hydroxyapatite (HAP), an osteogenic component, and roxithromycin (ROX), an antibacterial active component. Scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR) confirmed the hierarchical architecture of the nanofiber-microgrid within the scaffold, as well as the successful loading of HAP and ROX. The incorporation of HAP enhanced the water absorption capacity of the composite scaffold, thus promoting cell adhesion and proliferation, as well as osteogenic differentiation. Furthermore, ROX resulted in effective antibacterial capability without any observable cytotoxicity. Finally, the scaffolds were applied to a rat calvarial defect model, and the results demonstrated that the 20% HAP group exhibited superior new bone formation without causing adverse reactions. Therefore, our findings present a promising strategy for designing and fabricating bioactive scaffolds for bone regeneration.

Feasibility and Preliminary Efficacy of α-Calcium Sulfate Hemihydrate in Socket Preservation: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: Tooth extraction procedures often lead to bone resorption, which can have adverse effects on the dimensions of the alveolar ridge. Research has shown that socket preservation techniques using bone graft substitutes can effectively minimize early bone loss in such cases. α-calcium sulfate hemihydrate (α-CSH) has garnered significant attention as a potential bone graft material due to its favorable properties, including osteoconductivity, angiogenic potential, and biocompatibility. Considering these facts, we developed a preliminary protocol for applying α-CSH in addressing alveolar bone loss following tooth extraction. OBJECTIVE: This research's general objective is to evaluate the feasibility and initial effectiveness of α-CSH as bone-inducing graft material for socket preservation after tooth extraction. METHODS: This preliminary clinical trial will involve 30 fresh extraction sockets from individuals aged 18-35 years. The participants will be divided into 2 groups: one group will receive α-CSH graft material after tooth extraction for socket preservation, while the other group will not receive any graft material. Throughout the study, the participants will be closely monitored for safety measures, which will include clinical examinations, radiographic imaging, and blood tests. Radiographic imaging will be used extensively to assist the progress of bone formation. RESULTS: The study commenced enrollment in August 2022 and is scheduled to conclude post assessments and analyses by the end of 2023. The results of the study are anticipated to be accessible in late 2024. CONCLUSIONS: This clinical study represents the initial investigation in humans to assess the feasibility and efficacy of α-CSH in alveolar bone regeneration. We hypothesize that the inclusion of α-CSH can greatly expedite the process of bone formation within fresh sockets, resulting in a swift restoration of bone height without the disadvantages associated with harvesting autogenous bone graft. TRIAL REGISTRATION: Indonesia Registry Center INA-D02FAHP; https://tinyurl.com/2jnf6n3s. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49922.

Mineral trioxide aggregate in membrane form as a barrier membrane in guided bone regeneration.

Background/purpose: In the field of conservative dentistry and endodontics, mineral trioxide aggregate (MTA), commonly used, possesses advantages such as biocompatibility, antimicrobial properties and osteogenic potential. This study investigated the feasibility of utilizing membrane form mineral trioxide aggregate (MTA) as a barrier membrane in guided bone regeneration (GBR) procedures. Materials and methods: Membranes were electrospun from three different formulations: 15 w/v% Polycaprolactone (PCL), 13 w/v% PCL + 2 w/v% MTA (2MTA), and 11 w/v% PCL + 4 w/v% MTA (4MTA). Physicochemical and mechanical properties of the electrospun membrane were compared, encompassing parameters such as surface morphology, fiber diameter distribution, chemical composition, phase identification, tensile stress, pH variation, and water contact angle. Moreover, the antimicrobial properties against of the electrospun membranes were assessed through direct exposure to streptococcus aureus (S. aureus) and candida albicans (C. albicans). Additionally, on the 7th day, biocompatibility and cell attachment were investigated with respect to L929 (fibroblast) and MC3T3 (pre-osteoblast) cells. Inhibition of L929 cell infiltration and the expression of osteogenic related genes including osteocalcin (OCN), alkaline phosphatase (ALP), and runt related transcription factor 2 (RUNX2) in MC3T3 cells on 7th and 14th days were also investigated. Results: PCL, 2MTA, and 4MTA exhibited no statistically differences in fiber diameter distribution and tensile stress. However, as the MTA content increased, wettability and pH also increased. Due to the elevated pH, 4MTA demonstrated the lowest viability S.aureus and C.albicans. All membranes were highly biocompatibility and promoted cell attachment, while effectively preventing L929 cell infiltration. Lastly 4MTA showed increase in OCN, ALP, and RUNX2 expression on both 7th and 14th day. Conclusion: The membrane form MTA possessed characteristics essential for a novel barrier membrane.

Nano-vibration exciter: Hypoxia-inducible factor 1 signaling pathway-mediated extracellular vesicles as bioactive glass substitutes for bone regeneration.

Bioactive glasses (BG) play a vital role in angiogenesis and osteogenesis through releasing functional ions. However, the rapid ion release in the early stage will cause excessive accumulation of metal ions, which in turn leads to obvious cytotoxicity, long-term inflammation, and bone repair failure. Inspired by the vibration exciter, small extracellular vesicles (sEVs) obtained by treating mesenchymal stem cells with copper-doped bioactive glass (CuBG-sEVs), is prepared as a nano-vibration exciter. The nano-vibration exciter can convert the ion signals of CuBG into biochemical factor signals through hypoxia-inducible factor 1 (HIF-1) signaling pathway and its activated autophagy, so as to better exert the osteogenic activity of BG. The results showed that CuBG extracts could significantly improve the enrichment of key miRNAs and increase the yield of CuBG-sEVs by activating HIF-1 signaling pathway and its activated autophagy. Cell experiments showed that CuBG-sEVs are favor to cell recruitment, vascularization and osteogenesis as the enrichment of key miRNAs. The animal experiments results showed that CuBG-sEVs stimulated angiogenesis mediated by CD31 and promoted bone regeneration by activating signaling pathways related to osteogenesis. These findings underscored the significant potential of sEVs as alternative strategies to better roles of BG.

A Microenvironment-Responsive, Controlled Release Hydrogel Delivering Embelin to Promote Bone Repair of Periodontitis via Anti-Infection and Osteo-Immune Modulation.

Periodontitis, a prevalent chronic inflammatory disease, poses significant challenges for effective treatment due to its complex etiology involving specific bacteria and the inflammatory immune microenvironment. Here, this study presents a novel approach for the targeted treatment of periodontitis utilizing the immunomodulatory and antibacterial properties of Embelin, a plant-derived compound, within an injectable hydrogel system. The developed Carboxymethyl Chitosan-Oxidized Dextran (CMCS-OD) hydrogel formed via dynamic chemical bonds exhibited self-healing capabilities and pH-responsive behavior, thereby facilitating the controlled release of Embelin and enhancing its efficacy in a dynamic oral periodontitis microenvironment. This study demonstrates that this hydrogel system effectively prevents bacterial invasion and mitigates excessive immune response activation. Moreover, it precisely modulates macrophage M1/M2 phenotypes and suppresses inflammatory cytokine expression, thereby fostering a conducive environment for bone regeneration and addressing periodontitis-induced bone loss. These findings highlight the potential of the approach as a promising strategy for the clinical management of periodontitis-induced bone destruction.

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.

Preliminary study on the preparation of antler powder/chitosan/ß-glycerophosphate sodium/polyvinyl alcohol porous hydrogel scaffolds and their osteogenic effects.

Introduction: The production of bone-like structural scaffolds through bone tissue engineering technology is a promising method for bone regeneration to repair bone defects. Deer antler, an easily harvested and abundantly sourced initial bone tissue structure, resembles the composition and structure of human cancellous bone and can serve as a new material for allogeneic bone transplantation. Methods: This study involved the preparation and characterization of antler powder/chitosan/ß-glycerophosphate sodium/polyvinyl alcohol (AP/CS/ß-GP/PVA) porous hydrogel scaffolds to verify their material properties and osteogenic mechanisms. The microstructure, hydrophilicity, and mechanical properties of the scaffolds were studied using Scanning Electron Microscopy (SEM), contact angle measurement, and a universal material testing machine. The interactions between the various components were investigated using Fourier-Transform Infrared Spectroscopy (FTIR). Biocompatibility, osteogenic properties, and expression of osteogenesis-related proteins of the scaffolds were evaluated through Cell Counting Kit-8 (CCK-8) assays, alkaline phosphatase staining, Alizarin Red staining, live/dead cell staining, and Western blot analysis. Results: The results showed that as the content of deer antler powder increased, both the hydrophilicity and mechanical properties of the scaffold materials improved, while the porosity slightly decreased with an increase in deer antler powder content. Cell culture experiments demonstrated that scaffolds with a higher proportion of deer antler powder were beneficial for the proliferation and differentiation of mouse pre-osteoblast (MC3T3-E1) cells, with the scaffolds containing 10% and 8% deer antler powder showing the best effects. The upregulation of RUNX2, OCN, OSX, and OPN protein expression may promote differentiation. Discussion: Therefore, the AP/CS/ß-GP/PVA hydrogel scaffolds have the potential to become a promising biomaterial for bone tissue engineering.

3D-printed bone regeneration scaffolds modulate bone metabolic homeostasis through vascularization for osteoporotic bone defects.

The treatment of osteoporotic bone defects poses a challenge due to the degradation of the skeletal vascular system and the disruption of local bone metabolism within the osteoporotic microenvironment. However, it is feasible to modulate the disrupted local bone metabolism imbalance through enhanced vascularization, a theory termed "vascularization-bone metabolic balance". This study developed a 3D-printed polycaprolactone (PCL) scaffold modified with EPLQLKM and SVVYGLR peptides (PCL-SE). The EPLQLKM peptide attracts bone marrow-derived mesenchymal stem cells (BMSCs), while the SVVYGLR peptide enhances endothelial progenitor cells (EPCs) vascular differentiation, thus regulating bone metabolism and fostering bone regeneration through the paracrine effects of EPCs. Further mechanistic research demonstrated that PCL-SE promoted the vascularization of EPCs, activating the Notch signaling pathway in BMSCs, leading to the upregulation of osteogenesis-related genes and the downregulation of osteoclast-related genes, thereby restoring bone metabolic balance. Furthermore, PCL-SE facilitated the differentiation of EPCs into "H"-type vessels and the recruitment of BMSCs to synergistically enhance osteogenesis, resulting in the regeneration of normal microvessels and bone tissues in cases of femoral condylar bone defects in osteoporotic SD rats. This study suggests that PCL-SE supports in-situ vascularization, remodels bone metabolic translational balance, and offers a promising therapeutic regimen for osteoporotic bone defects.