Bioactive nanocomposite hydrogel enhances postoperative immunotherapy and bone reconstruction for osteosarcoma treatment.

Osteosarcoma, a malignant bone tumor often characterized by high hedgehog signaling activity, residual tumor cells, and substantial bone defects, poses significant challenges to both treatment response and postsurgical recovery. Here, we developed a nanocomposite hydrogel for the sustained co-delivery of bioactive magnesium ions, anti-PD-L1 antibody (αPD-L1), and hedgehog pathway antagonist vismodegib, to eradicate residual tumor cells while promoting bone regeneration post-surgery. In a mouse model of tibia osteosarcoma, this hydrogel-mediated combination therapy led to remarkable tumor growth inhibition and hence increased animal survival by enhancing the activity of tumor-suppressed CD8+ T cells. Meanwhile, the implanted hydrogel improved the microenvironment of osteogenesis through long-term sustained release of Mg2+, facilitating bone defect repair by upregulating the expression of osteogenic genes. After 21 days, the expression levels of ALP, COL1, RUNX2, and BGLAP in the Vis-αPD-L1-Gel group were approximately 4.1, 5.1, 5.5, and 3.4 times higher than those of the control, respectively. We believe that this hydrogel-based combination therapy offers a potentially valuable strategy for treating osteosarcoma and addressing the tumor-related complex bone diseases.

Photothermal switch by gallic acid-calcium grafts synthesized by coordination chemistry for sequential treatment of bone tumor and regeneration.

The residual bone tumor and defects which is caused by surgical therapy of bone tumor is a major and important problem in clinicals. And the sequential treatment for irradiating residual tumor and repairing bone defects has wildly prospects. In this study, we developed a general modification strategy by gallic acid (GA)-assisted coordination chemistry to prepare black calcium-based materials, which combines the sequential photothermal therapy of bone tumor and bone defects. The GA modification endows the materials remarkable photothermal properties. Under the near-infrared (NIR) irradiation with different power densities, the black GA-modified bone matrix (GBM) did not merely display an excellent performance in eliminating bone tumor with high temperature, but showed a facile effect of the mild-heat stimulation to accelerate bone regeneration. GBM can efficiently regulate the microenvironments of bone regeneration in a spatial-temporal manner, including inflammation/immune response, vascularization and osteogenic differentiation. Meanwhile, the integrin/PI3K/Akt signaling pathway of bone marrow mesenchymal stem cells (BMSCs) was revealed to be involved in the effect of osteogenesis induced by the mild-heat stimulation. The outcome of this study not only provides a serial of new multifunctional biomaterials, but also demonstrates a general strategy for designing novel blacked calcium-based biomaterials with great potential for clinical use.

Injectable double-crosslinked bone cement with enhanced bone adhesion and improved osteoporotic pathophysiological microenvironment for osteoregeneration in osteoporosis.

The osteoporotic bone defect caused by excessive activity of osteoclasts has posed a challenge for public healthcare. However, most existing bioinert bone cement fails to effectively regulate the pathological bone microenvironment and reconstruct bone homeostasis in the presence of osteoclast overactivity and osteoblast suppression. Herein, inspired by natural bone tissue, an in-situ modulation system for osteoporotic bone regeneration is developed by fabricating an injectable double-crosslinked PEGylated poly(glycerol sebacate) (PEGS)/calcium phosphate cement (CPC) loaded with sodium alendronate (ALN) (PEGS/CPC@ALN) adhesive bone cement. By incorporating ALN, the organic-inorganic interconnection within PEGS/CPC@ALN results in a 100 % increase in compression modulus and energy dissipation efficiency. Additionally, PEGS/CPC@ALN effectively adheres to the bone by bonding with amine and calcium ions present on the bone surface. Moreover, this in-situ regulation system comprehensively mitigates excessive bone resorption through the buffering effect of CPC to improve the acidic microenvironment of osteoporotic bone and the release of ALN to inhibit hyperactive osteoclasts, and facilitates stem cell proliferation and differentiation into osteoblasts through calcium ion release. Overall, the PEGS/CPC@ALN effectively regulates the pathological microenvironment of osteoporosis while promoting bone regeneration through synergistic effects of drugs and materials, thereby improving bone homeostasis and enabling minimally invasive treatment for osteoporotic defects.

3D-Printed-Cryogel-Impregnated Functionalized Scaffold Augments Bone Regeneration in Critical Tibia Fracture in Goat.

Critical-size bone trauma injuries present a significant clinical challenge because of the limited availability of autografts. In this study, a photocurable composite comprising of polycaprolactone, polypropylene fumarate, and nano-hydroxyapatite (nHAP) (P─P─H) is printed, which shows good osteoconduction in a rat model. A cryogel composed of gelatin-nHAP (GH) is developed to incorporate osteogenic components, specifically bone morphogenetic protein-2 (BMP-2) and zoledronic acid (ZA), termed as GH+B+Z, which is investigated for osteoinductive property in a rat model. Further, a 3D-printed P─P─H scaffold impregnated with GH+B+Z is designed and implanted in a critical-size defect (25 × 10 × 5 mm) in goat tibia. After 4 months, the scaffold is well-integrated with adjacent native bone, with osteoinduction observed in the cryogel-filled region and osteoconduction over the printed scaffold. X-ray radiography and micro-CT analysis showed bone in-growth in the treatment group with 45 ± 1.4% bone volume/tissue volume (BV/TV), while the defect remained unhealed in the control group with BV/TV of 10.5 ± 0.5%. Histology showed significant cell infiltration and matrix deposition over the printed P─P─H scaffold and within the GH cryogel site in the treatment group. Immunohistochemical staining depicted significantly higher normalized collagen I intensity in the treatment group (34.45 ± 2.61%) compared to the control group (4.22 ± 0.78).

Clinical and radiographic changes following transcrestal sinus augmentation: A scoping review of the last 25 years.

INTRODUCTION: Maxillary sinus floor elevation is a surgical procedure intended to increase the volume of the bone vertically to accommodate dental implant placement. This intervention is frequently required for implant installation in the posterior maxilla, where the bone may be insufficient for securing implants of necessary length and stability. Sinus floor elevation can be completed either through a direct approach with a "window" through the lateral wall of the alveolar ridge or an indirect "transcrestal/transalveolar" sinus floor elevation (TSFE), which accesses the sinus floor through the crest of the edentulous ridge. Our study aims to provide a comprehensive scoping review of research conducted over the past 25 years on TSFE, specifically. METHODS: A literature search aimed at identifying pertinent literature for the purpose of this PRISMA-ScR-compliant scoping review was conducted. Only randomized controlled trials, non-randomized controlled trials, prospective cohort studies, and case series that met the eligibility criteria were selected. Relevant data from these studies were extracted. Primary outcome measures included radiographic bone levels and implant failure >5 years. Secondary outcome measures included implant stability at time of placement and complications. Interventions reported in the selected studies were grouped based on treatment modality, which were then compared with the control therapy (traditional osteotome technique) after a minimum of 12 months healing period. RESULTS: Our search yielded 633 records, and after deduplication, 574 of these were screened. Application of the eligibility criteria led to the inclusion of 37 articles in the final selection. Case selection for included studies enrolling subjects: Four different transcrestal sinus elevation treatment modalities were identified: (a) osteotome, (b) piezoelectric surgery, (c) osseodensification, and (d) hydraulic techniques. Due to the heterogeneity of the studies, no superior approach for TSFE could be identified. Overall, all techniques demonstrated high implant survival rates. CONCLUSION: Comprehensive understanding of the patient's medical history, available armamentarium, and post-operative complications/management strategies are all essential to the completion of a successful TSFE approach for implant placement in the posterior maxilla, regardless of the treatment modality used.

The impact of collagen membrane fixation protocols on volume stability in horizontal ridge augmentation in the aesthetic area: A retrospective study.

OBJECTIVES: This study aimed to evaluate the impact of different collagen membran fixation protocols on the volume stability in horizontal ridge augmentation in the aesthetic area. METHODS: A total of 48 patients with 65 augmented sites were included in this study. Implants were placed in the aesthetic region, and simultaneous guided bone regeneration (GBR) surgery was performed for horizontal ridge augmentation. Participants were divided into four groups, each comprising 12 patients, based on different absorbable collagen membrane fixation protocols. Group 1: without fixation; Group 2: fixation with absorbable sutures; Group 3: fixation with titanium pins; Group 4: fixation with titanium pins and absorbable sutures. Cone beam computed tomography (CBCT) was performed immediately after surgery and at 6 months post-surgery, respectively. The horizontal thickness of the augmented region was analyzed for volume stability at the implant shoulder (H0) and 1-5 mm apical to the implant shoulder (H1-H5). Changes in labial thickness during bone healing were calculated as absolute values (mm) and relative values (%). RESULTS: After 6 months of bone healing, horizontal thickness was significantly reduced at all levels (H0-H5) in all groups compared to immediate post-surgery results (p < 0.05). At H1-H5, horizontal bone loss in group 1 was significantly higher than in the other three groups (p < 0.05). Group 4 exhibited significantly less horizontal bone loss compared to group 2 at H0-H2 (p < 0.05) and group 4 compared to group 3 at H0-H1 (p < 0.05). No significant difference in horizontal bone loss between groups 2 and 3 was detected at H0-H5 (p > 0.05). CONCLUSION: Guided bone regeneration in the aesthetic area with additional membrane fixation demonstrated superior volume stability of the augmented region compared to cases without fixation. There was no significant difference in bone volume stability between membrane fixation with titanium pins and fixation with absorbable sutures. However, the combined use of pins and absorbable sutures yielded superior volume stability.

Horizontal Guided Bone Regeneration of the Posterior Mandible to Allow Implant Placement: 1-Year Prospective Study Results.

OBJECTIVE: Assess whether horizontal ridge augmentation with guided bone regeneration (GBR) using deproteinized bovine bone mineral (DBBM), autologous bone, and a resorbable collagen membrane supports successful implant placement. MATERIALS AND METHODS: This open, prospective, single-cohort, multicenter clinical study included patients with ridge defects that required GBR prior to implant insertion. The primary endpoint was radiologically assessed bone gain after 8 months post-GBR, measured at the center of planned implant sites. Secondary endpoints included implant survival and success, marginal bone levels (MBLs), MBL changes, and soft tissue health. RESULTS: Of 45 patients evaluated 8 months post-GBR, nine experienced dehiscence in the first 3 weeks of the healing period. GBR led to radiologically determined mean bone width gain of 4.0 ± 1.5 mm and 4.8 ± 1.7 mm, measured 1 and 3 mm from the top of the crest, respectively, allowing successful implant placement in 44 patients (97.8%). The cumulative implant survival and success rates were 98.9% and 95.5%, respectively. MBLs were stable: -1.18 ± 0.64 mm at definitive prosthesis placement (DPP) and - 1.07 ± 0.74 mm at 1 year. Soft tissue health and esthetics (plaque and bleeding indices, papilla, keratinized mucosa, and pink esthetic score) improved from DPP to 1 year. Patients were highly satisfied with implant function and esthetics, and their oral health-related quality of life improved. CONCLUSIONS: GBR using DBBM and a collagen membrane offered a safe and effective treatment option for horizontal ridge augmentation sufficient to support implant-based tooth rehabilitation. TRIAL REGISTRATION: Registered at ClinicalTrials.gov NCT03028922 (registrations sites, as above listed affiliations, first posted January 23, 2017).

Hypoxia-Mimicking Mediated Macrophage-Elimination of Erythrocytes Promotes Bone Regeneration via Regulating Integrin αvß3/Fe2+-Glycolysis-Inflammation.

Erythrocytes are the dominant component of a blood clot in terms of volume and number. However, longstanding compacted erythrocytes in blood clots form a physical barrier and make fibrin mesh more anti-fibrinolytic, thus impeding infiltration of mesenchymal stem cells. The necrosis or lysis of erythrocytes that are not removed timely can also lead to the release of pro-inflammatory toxic metabolites, interfering with bone regeneration. Proper bio-elimination of erythrocytes is essential for an undisturbed bone regeneration process. Here, hypoxia-mimicking is applied to enhance macrophage-elimination of erythrocytes. The effect of macrophage-elimination of erythrocytes on the macrophage intracellular reaction, bone regenerative microenvironment, and bone regeneration outcome is investigated. Results show that the hypoxia-mimicking agent dimethyloxalylglycine successfully enhances erythrophagocytosis by macrophages in a dose-dependent manner primarily by up-regulating the expression of integrin αvß3. Increased phagocytosed erythrocytes then regulate macrophage intracellular Fe2+-glycolysis-inflammation, creating an improved bone regenerative microenvironment characterized by loose fibrin meshes with down-regulated local inflammatory responses in vivo, thus effectively promoting early osteogenesis and ultimate bone generation. Modulating macrophage-elimination of erythrocytes can be a promising strategy for eradicating erythrocyte-caused bone regeneration hindrance and offers a new direction for advanced biomaterial development focusing on the bio-elimination of erythrocytes.

Comparison of Khoury's Bone Shell Technique vs Titanium-reinforced Polytetrafluoroethylene Membrane for 3D-bone Augmentation in Atrophic Posterior Mandible: A Randomized Clinical Trial.

AIM: This study was designed to compare between the use of Khoury's bone shell technique vs titanium-reinforced PTFE membrane for 3D-ridge augmentation of atrophic posterior mandible. MATERIALS AND METHODS: Sixteen patients were equally and randomly assigned to either the Khoury or PTFE group. In Khoury group, a mandibular bone block was harvested, split and then fixed to augment the mandibular defect using osteosynthesis screws. In PTFE group, augmentation was achieved using Titanium-reinforced PTFE membranes fixed with bone tacks/screws. A mixture of autogenous and xenogenic graft material at a 1:1 ratio was used in both groups. Vertical and horizontal bone gain were obtained using cone-beam computed tomography (CBCT). Preoperative dimensions were compared with the final dimensions obtained 6 months postoperatively. RESULTS: No significant complications or neurosensory dysfunction were encountered. A solitary patient in the Khoury group experienced limited wound dehiscence, which was treated conservatively. For both groups, there were no significant differences between preoperative and postoperative vertical (p = 0.849 and 0.569) and horizontal (p = 0.778 and 0.367) dimensions. CONCLUSION: No significant differences exist between the augmentation dimension which can be obtained using either Khoury of Ti-PTFE membranes. CLINICAL SIGNIFICANCE: Both approaches are delicate and necessitate surgical expertise and experience. Both techniques can be used to achieve predictable augmentation results with a low rate of complications. How to cite this article: Shaker AES, Salem AS, El-Farag SAA, et al. Comparison of Khoury's Bone Shell Technique vs Titanium-reinforced Polytetrafluoroethylene Membrane for 3D-bone Augmentation in Atrophic Posterior Mandible: A Randomized Clinical Trial. J Contemp Dent Pract 2024;25(6):518-526.

Comparison of three approaches for treating the bony access window in lateral sinus floor elevation: a retrospective analysis.

The aim of this study was to retrospectively determine the effects of applying different treatment methods to the bony access window on the healing outcomes in lateral sinus floor elevation (SFE). Lateral SFE with implant placement was performed in 131 sinuses of 105 patients. The following three treatment methods were applied to the bony access window: application of a collagen barrier (group CB), repositioning the bone fragment (group RW) and untreated (group UT). Radiographic healing in the window area, augmented bone height changes and marginal bone level changes were examined. Mixed logistic and mixed linear models were analyzed. Over 4.3 ± 1.4 years of follow-up, the implant survival rate was 100% in groups CB and UT, and 96.9% in group RW. The treatment applied to the window did not significantly influence the radiographic healing in the window area, augmented bone height changes or marginal bone level changes (p > 0.05). The healed window areas had generally flat morphologies and were fully corticalized. The mean changes in the augmented bone were less than 1.5 mm in all groups. Marginal bone level changes were minimal. In conclusion, Healing outcomes were not different among three different methods to treat the bony access window in lateral SFE.

Enhancing osteoblast differentiation and bone repair: The priming effect of photobiomodulation on adipose stromal cells.

Cellular therapy using adipose tissue-derived mesenchymal stromal cells (at-MSCs) has garnered attention for the treatment of bone defects. Therefore, preconditioning strategies to enhance the osteogenic potential of at-MSCs could optimize cell therapy outcomes, and photobiomodulation (PBM) therapy has emerged as an effective, noninvasive, and low-cost alternative. This study explored the impacts of PBM on at-MSCs differentiation and the subsequent repair of bone defects treated with cell injection. Rat at-MSCs were cultured and irradiated (at-MSCsPBM) following the PBM protocol (660 nm; 20 mW; 0.714 W/cm2; 0.14 J; 5 J/cm2). Cellular differentiation was assessed based on the expression of gene and protein markers. Reactive oxygen species (ROS) were detected using fluorescence. At-MSCsPBM were injected into 5-mm calvarial lesions, and bone formation was analyzed using micro-CT and histological evaluations. At-MSCs were used as control. Data were analyzed using the ANOVA or t-test. At-MSCsPBM exhibited high levels of gene and protein runt-related transcription factor-2 (Runx2) and alkaline phosphatase (Alp) expression. PBM increased ALP activity and significantly reduced ROS levels. In addition, PBM increased the expression of Wnt pathway-associated genes. In vivo, there was an increase in the morphometric parameters, including bone volume, percentage of bone volume, bone surface area, and trabecular number, in at-MSCsPBM-treated defects compared with those in the control. These findings suggest that PBM enhances the osteogenic potential of at-MSCs, thereby supporting the advancement of improved cellular therapies for bone regeneration.

Biomimetic mineralization of collagen from fish scale to construct a functionally gradient lamellar bone-like structure for guided bone regeneration.

Wide used guided bone regeneration (GBR) membrane materials, such as collagen, Teflon, and other synthesized polymers, present a great challenge in term of integrating the mechanical property and degradation rate when addressing critical bone defects. Therefore, inspired by the distinctive architecture of fish scales, this study utilized epigallocatechin gallate to modify decellularized fish scales following biomimetic mineralization to fabricate a GBR membrane that mimics the structure of lamellar bone. The structure, physical and chemical properties, and biological functions of the novel GBR membrane were evaluated. Results indicate that the decellularized fish scale with 5 remineralization cycles (5R-E-DCFS) exhibited a composite and structure similar to natural bone and had a special functionally gradient mineral contents character, demonstrating excellent mechanical properties, hydrophilicity, and degradation properties. In vitro, the 5R-E-DCFS membrane exhibited excellent cytocompatibility promoting Sprague-Dawley (SD) rat bone marrow mesenchymal stem cell proliferation and differentiation up-regulating the expression of osteogenic-related genes and proteins. Furthermore, in vivo, the 5R-E-DCFS membrane promoted the critical skull bone defects of SD rats repairment and regeneration. Therefore, this innovative biomimetic membrane holds substantial clinical potential as an ideal GBR membrane with mechanical properties for space-making and suitable degradation rate for bone regeneration to manage bone defects.

Pre-vascularized porous gelatin-coated ß-tricalcium phosphate scaffolds for bone regeneration: an in vivo and in vitro investigation.

Vascularization is vital in bone tissue engineering, supporting development, remodeling, and regeneration. Lack of vascularity leads to cell death, necessitating vascularization strategies. Angiogenesis, forming new blood vessels, provides crucial nutrients and oxygen. Pre-vascularized gelatin-coated ß-tricalcium phosphate (G/ß-TCP) scaffolds show promise in bone regeneration and vascularization. Our study evaluates G/ß-TCP scaffolds' osteogenic and angiogenic potential in vitro and a canine model with vascular anastomosis. Channel-shaped G/ß-TCP scaffolds were fabricated using foam casting and sintering of a calcium phosphate/silica slurry-coated polyurethane foam, then coated with cross-linked gelatin. Buccal fat pad-derived stem cells (BFPdSCs) were seeded onto scaffolds and assessed over time for adhesion, proliferation, and osteogenic capacity using scanning electron microscopy (SEM), 4,6-diamidino-2-phenylindole (DAPI) staining, Alamar blue, and alkaline phosphatase (ALP) assays. Scaffolds were implanted in a canine model to evaluate osteogenesis and angiogenesis by histology and CT scans at 12 wk. Our studies showed preliminary results for G/ß-TCP scaffolds supporting angiogenesis and bone regeneration. In vitro analyses demonstrated excellent proliferation/viability, with BFPdSCs adhering and increasing on the scaffolds. ALP activity and protein levels increased, indicating osteogenic differentiation. Examination of tissue samples revealed granulation tissue with a well-developed vascular network, indicating successful angiogenesis and osteogenesis was further confirmed by a CT scan. In vivo, histology revealed scaffold resorption. However, scaffold placement beneath muscle tissue-restricted bone regeneration. Further optimization is needed for bone regeneration applications.

Magnesium Nanocomposite Hydrogel Reverses the Pathologies to Enhance Mandible Regeneration.

The healing of bone defects after debridement in medication-related osteonecrosis of the jaw (MRONJ) is a challenging medical condition with impaired angiogenesis, susceptible infection, and pro-inflammatory responses. Magnesium (Mg) nanocomposite hydrogel is developed to specifically tackle multiple factors involved in MRONJ. Mg-oxide nanoparticles tune the gelation kinetics in the reaction between N-hydroxysuccinimide-functionalized hyperbranched poly (ethylene glycol) and proteins. This reaction allows an enhanced mechanical property after instant solidification and, more importantly, also stable gelation in challenging environments such as wet and hemorrhagic conditions. The synthesized hydrogel guides mandible regeneration in MRONJ rats by triggering the formation of type H vessels, activating Osterix+ osteoprogenitor cells, and generating anti-inflammatory microenvironments. Additionally, this approach demonstrates its ability to suppress infection by inhibiting specific pathogens while strengthening stress tolerance in the affected alveolar bone. Furthermore, the enhanced osteogenic properties and feasibility of implantation of the hydrogel are validated in mandible defect and iliac crest defect created in minipigs, respectively. Collectively, this study offers an injectable and innovative bone substitute to enhance mandible defect healing by tackling multiple detrimental pathologies.

Osseointegration of Anodized vs. Sandblasted Implant Surfaces in a Guided Bone Regeneration Acute Dehiscence-Type Defect: An In Vivo Experimental Mandibular Minipig Model.

OBJECTIVES: This controlled preclinical study analyzed the effect of implant surface characteristics on osseointegration and crestal bone formation in a grafted dehiscence defect minipig model. MATERIAL AND METHODS: A standardized 3 mm × 3 mm acute-type buccal dehiscence minipig model grafted with deproteinized bovine bone mineral and covered with a porcine collagen membrane after 2 and 8 weeks of healing was utilized. Crestal bone formation was analyzed histologically and histomorphometrically to compare three implant groups: (1) a novel, commercially available, gradient anodized (NGA) implant, to two custom-made geometric replicas of implant "1," (2) a superhydrophilic micro-rough large-grit sandblasted and acid-etched surface, and (3) a relatively hydrophobic micro-rough large-grit sandblasted and acid-etched surface. RESULTS: At 2 and 8 weeks, there was no difference between the amount and height of newly formed bone (NBH, new bone height; BATA, bone area to total area) for any of the groups (p > 0.05). First bone-to-implant contact (fBIC) and vertical bone creep (VBC) at 2 and 8 weeks were significantly increased for Groups 2 and 3 compared to Group 1 (p < 0.05). At 8 weeks, osseointegration in the dehiscence (dehiscence bone-implant-contact; dBIC) was significantly higher for Groups 2 and 3 compared to Group 1 (p < 0.05). CONCLUSIONS: The amount of newly formed bone (BATA) and NBH was not influenced by surface type. However, moderately rough surfaces demonstrated significantly superior levels of osseointegration (dBIC) and coronal bone apposition (fBIC) in the dehiscence defect compared to the NGA surface at 2 and 8 weeks. TRIAL REGISTRATION: For this type of study, clinical trial registration is not required. This study was conducted at the Biomedical Department of Lund University (Lund, Sweden) and approved by the local Ethics Committee of the University (M-192-14).

Evaluation of the Bone Formation Potential of Collagen/ß-TCP/Ginger Extract Scaffold Loaded with Mesenchymal Stem Cells in Rat Animal model: A Stereological Study.

Tissue engineering offers a new horizon for restoring the function of damaged tissues and organs. Here, bone regeneration potential of three-dimensional (3D) scaffold made of collagen/beta-tricalcium phosphate/ginger hydroalcoholic extract (COL-ß-TCP-GIN) loaded with stem cells was evaluated. The scaffolds with different component ratios were fabricated using a freeze dryer to obtain the optimum composition. The scaffolds' chemical, physical, and biological characteristics were evaluated using scanning electron microscope, fourier transform infrared spectroscopy, tensile testing machine, and cytotoxicity assay. The optimum scaffold's bone repairing potential was assessed with loaded synovial membrane mesenchymal stem cells (SM-MSCs) in mandibular bone defect of a rat animal model after two months. The ß-TCP component up to 30% could increase the tensile strength of the freeze-dried scaffold. In comparison, the GIN up to 5% was selected as a sufficient amount to be incorporated with the scaffolds. The morphology of scaffolds showed a suitable porosity for cells to proliferate and migrate. In vitro cytotoxicity results showed that GIN increased the cell viability up to 7 days. Regarding in vivo bone regeneration study, histopathology and stereology assessments showed the mandibular bone formation in COL/ß-TCP/GIN scaffolds with SM-MSCs group significantly increased compared to COL/ß-TCP/GIN without cells and sham groups. These results demonstrated the effectiveness of COL/ß-TCP/GIN scaffold with SM-MSCs to induce bone formation, and this composite can be applied in dental and reconstructive surgery. Supplementary Information: The online version contains supplementary material available at 10.1007/s12663-022-01829-9.

Graphene Oxide Quantum Dots-Preactivated Dental Pulp Stem Cells/GelMA Facilitates Mitophagy-Regulated Bone Regeneration.

Background: In bone tissue engineering (BTE), cell-laden scaffolds offer a promising strategy for repairing bone defects, particularly when host cell regeneration is insufficient due to age or disease. Exogenous stem cell-based BTE requires bioactive factors to activate these cells. Graphene oxide quantum dots (GOQDs), zero-dimensional derivatives of graphene oxide, have emerged as potential osteogenic nanomedicines. However, constructing biological scaffolds with GOQDs and elucidating their biological mechanisms remain critical challenges. Methods: We utilized GOQDs with a particle size of 10 nm, characterized by a surface rich in C-O-H and C-O-C functional groups. We developed a gelatin methacryloyl (GelMA) hydrogel incorporated with GOQDs-treated dental pulp stem cells (DPSCs). These constructs were transplanted into rat calvarial bone defects to estimate the effectiveness of GOQDs-induced DPSCs in repairing bone defects while also investigating the molecular mechanism underlying GOQDs-induced osteogenesis in DPSCs. Results: GOQDs at 5 µg/mL significantly enhanced the osteogenic differentiation of DPSCs without toxicity. The GOQDs-induced DPSCs showed active osteogenic potential in three-dimensional cell culture system. In vivo, transplantation of GOQDs-preactivated DPSCs/GelMA composite effectively facilitated calvarial bone regeneration. Mechanistically, GOQDs stimulated mitophagy flux through the phosphatase-and-tensin homolog-induced putative kinase 1 (PINK1)/Parkin E3 ubiquitin ligase (PRKN) pathway. Notably, inhibiting mitophagy with cyclosporin A prevented the osteogenic activity of GOQDs. Conclusion: This research presents a well-designed bionic GOQDs/DPSCs/GelMA composite scaffold and demonstrated its ability to promote bone regeneration by enhancing mitophagy. These findings highlight the significant potential of this composite for application in BTE and underscore the crucial role of mitophagy in promoting the osteogenic differentiation of GOQDs-induced stem cells.

Simple-Challenging-Difficult (SCD) Difficulty Classification for Vertical Bone Augmentation.

OBJECTIVE: To propose a new difficulty classification for vertical bone augmentation (VBA) based on different defect morphologies. OVERVIEW: VBA procedures for dental implant placement present significant biological and technical challenges. Among the various techniques, guided bone regeneration (GBR) provides an optimal balance between the anticipated bone gain and the likelihood of postoperative complications. Understanding the specific configuration of defects and adjacent bone peaks is essential for tailoring treatment strategies and improving outcomes. The proposed Simple-Challenging-Difficult (SCD) difficulty classification was based on defect morphology (V-shaped, U-shaped, VV-shaped), including defect size (Height: < 5 mm, 5-8 mm, and > 8 mm), proximity of neighboring bony walls (Width: < 10 mm, 10-20 mm, and > 20 mm), as well as predictability of treatment outcomes. CONCLUSIONS: The proposed difficulty classification for VBA serves as a guide for selecting the most appropriate GBR treatment modality and sequence for safe and predictable management of VBA in implant therapy. In addition, when determining the preferred treatment, it is again essential to consider site-specific and patient-related factors alongside the clinician's surgical experience and skill. CLINICAL SIGNIFICANCE: Identifying defect patterns and bone peak structures is crucial, and the proposed classification assists in decision-making in VBA treatment.

Proanthocyanidins modification of the mineralized collagen scaffold based on synchronous self-assembly/mineralization for bone regeneration.

Proteoglycans (PG) is crucial for regulating collagen formation and mineralization during bone tissue development. A wide variety of PG-modified collagen scaffolds have been proposed for bone engineering application to promote biological responses and work as artificial matrices that guide tissue regeneration. However, poor performance of theses biomaterials against infections has led to an unmet need for clinical prevention. Therefore, we utilized proanthocyanidins (PA) to simulate the functions of PG, including mediating the collagen assembly and intrafibrillar mineralization, to optimize scaffolds performance. The excellent antibacterial properties of PA can endow the scaffolds with anti-infection effects in the process of tissue regeneration. When PA was added during fibrillogenesis, the collagen fibrils appeared irregular aggregation and the mineralization degree was reduced. In contrast, the addition of PA after collagen self-assembly improved the latter's ability to act as a deposition template and remarkably promoted mineral ions infiltration, thus enhancing intrafibrillar mineralization. The PA-modified scaffold displayed a highly hydrophilicity behaviour and long-term resistance to degradation. The sustained release of PA effectively inhibited the activity of Staphylococcus aureus. The scaffold also showed excellent biocompatibility and improved bone regeneration in calvarial critical-size defect models. The application of PA enables a dual-function scaffold with favourable intrafibrillar mineralization and anti-bacterial properties for bone regeneration.

Bifunctional mesoporous HMUiO-66-NH2 nanoparticles for bone remodeling and ROS scavenging in periodontitis therapy.

Periodontal bone defects represent an irreversible consequence of periodontitis associated with reactive oxygen species (ROS). However, indiscriminate removal of ROS proves to be counterproductive for tissue repair and insufficient for addressing existing bone defects. In the treatment of periodontitis, it is crucial to rationally alleviate local ROS while simultaneously promoting bone regeneration. In this study, Zr-based large-pore hierarchical mesoporous metal-organic framework (MOF) nanoparticles (NPs) HMUiO-66-NH2 were successfully proposed as bifunctional nanomaterials for bone regeneration and ROS scavenging in periodontitis therapy. HMUiO-66-NH2 NPs demonstrated outstanding biocompatibility both in vitro and in vivo. Significantly, these NPs enhanced the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) under normal and high ROS conditions, upregulating osteogenic gene expression and mitigating oxidative stress. Furthermore, in vivo imaging revealed a gradual degradation of HMUiO-66-NH2 NPs in periodontal tissues. Local injection of HMUiO-66-NH2 effectively reduced bone defects and ROS levels in periodontitis-induced C57BL/6 mice. RNA sequencing highlighted that differentially expressed genes (DEGs) are predominantly involved in bone tissue development, with notable upregulation in Wnt and TGF-ß signaling pathways. In conclusion, HMUiO-66-NH2 exhibits dual functionality in alleviating oxidative stress and promoting bone repair, positioning it as an effective strategy against bone resorption in oxidative stress-related periodontitis.