We explored the feasibility and efficacy of a degradable magnesium (Mg) alloy guided bone regeneration (GBR) in the treatment of bone defects after tooth extraction. A GBR membrane (MAR‐Gide (MG)) was used to treat a mandibular second molar (M2M)‐distal bone defect (DBD). In eight beagle dogs, bilateral mandibular second and fourth premolars were hemi‐sected. The distal roots were removed to create a two‐wall bony defect of dimension 5 mm × 5 mm × 5 mm to simulate M2M‐DBD. Thirty‐two bone defects were assigned randomly into four groups according to GBR membranes (MG and Bio‐Gide (BG)) applied and the time of killing (3 months and 6 months after surgery). The osteogenesis of bone defects and MG degradation were analyzed using micro‐CT, histology (staining, tartrate‐resistant acid phosphatase), and inductively coupled plasma mass spectrometry. MG did not increase the prevalence of infection, wound dehiscence, or subcutaneous emphysema compared with those using BG. Trabecular volume/total volume at 3 months (63.71 ± 10.4% vs. 59.97 ± 8.94%) was significantly higher in the group MG than that in the group BG. Implanted MG was degraded completely within 3 months, and “island‐shaped” new bone was found near MG degradation products. A significant difference was not found in vertical bone height or percent of new bone formation (45.44 ± 12.28% vs. 43.49 ± 7.12%) between the groups. The concentration of rare‐earth elements in mandibular lymph nodes of the group MG was significantly higher than that of the group BG (P ≤ 0.017) but did not lead to histopathological changes. In summary, MG exhibited good biocompatibility and clinical applicability compared with BG in vivo. The osteogenic effect of MG could be enhanced by regulating the degradation rate of Mg‐alloy.

Bone defect represents one of the most prevalent clinical conditions in orthopedics diseases, and the key to successful therapeutic outcomes lies in achieving early vascularization coupled with late-phase osteogenic differentiation. Growth factor delivery is among the most widely adopted strategies for bone tissue regeneration. However, achieving the spatiotemporal coupled regulation of vascularized bone regeneration remains a major challenge. Proprotein convertase subtilisin/kexin type 9 (PCSK9) exerts a pivotal role in bone metabolism. Our preliminary findings demonstrated that PCSK9 expression is upregulated during bone regeneration, while the supplementation of exogenous PCSK9 can enhance the osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSC). Based on these findings, we fabricated a composite hydrogel by adsorbing PCSK9 onto vascular-derived extracellular matrix (ECM) and incorporating vascular endothelial growth factor (VEGF) into gelatin methacryloyl (GelMA). Taking advantage of the distinct sustained-release profiles of these biomaterials, this hydrogel system was engineered to recapitulate the natural bone defect healing process, thereby enabling the coupled regulation of accelerated early vascularization and enhanced late-phase osteogenic differentiation. Both in vitro and in vivo experimental results confirmed that the constructed composite hydrogel can further potentiate the therapeutic efficacy of PCSK9 and achieve efficient vascularized bone regeneration. Mechanistically, our findings revealed that PCSK9 promotes the osteogenic differentiation of BMMSC via activation of the ERK signaling pathway. Collectively, the PCSK9- and VEGF-loaded composite hydrogel exhibits promising pro-angiogenic and pro-osteogenic coupling capabilities for bone regeneration, which provides novel therapeutic targets and innovative strategies for the clinical management of bone defects.

Magnesium alloys have attracted significant attention in recent years as biodegradable metals. However, their degradation mechanisms in vivo remain insufficiently understood. The present work investigates the degradation mechanism of AZ91 magnesium alloy in a critical-size rat defect model over an 8-week period in vivo, employing advanced characterization techniques such as transmission electron microscopy (TEM) and nanobeam electron diffraction (NBED). The degradation layer is observed to consist of three distinct sub-layers: a dense and compact poor crystallinity layer (PCL) layer primarily composed of calcium phosphate, a loose and porous amorphous layer (AL) of magnesium/calcium phosphate, and a hybrid layer (HL)layer containing degradation channels and composed of magnesium/calcium phosphate, layered double hydroxide (LDH), and magnesium hydroxide. The corrosion resistance of AZ91 is enhanced by the presence of the compact PCL layer, the uniform distribution of the Mg₁₇Al₁₂ phase, and the formation of impervious LDH at the corrosion interface. The degradation is primarily driven by micro-galvanic corrosion, which is influenced by the interaction between the Mg matrix and the Mg₁₇Al₁₂ phase. These findings provide critical insights into the stable degradation mechanism of Mg-Al alloys in vivo, advancing the development of biodegradable magnesium-based implants.

Background: To analyze and summarize the clinical efficacy of mucoperiosteal flap combined with perforation technique for tooth extraction in medication-related osteonecrosis of the jaw risk (MRONJ) population, and to provide clinical treatment options for such patients. Methods: This study included 51 patients receiving antiresorptive drug (ARD) treatment who underwent tooth extraction at the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology between November 2016 and February 2024. Preoperative clinical data were collected and analyzed. Based on their drug history, patients were categorized into two groups: (1) low-dose ARD group for patients with non-neoplastic lesion like osteoporosis (LDA), (2) high-dose ARD group for patients with bone metastatic lesions like breast cancer (HDA). All patients underwent tooth extraction using mucoperiosteal flap combined with perforation technique. Follow-up assessments were conducted at 1 week, 2 weeks, 1 month, 3 month and 6 months postoperatively. The primary evaluation outcome was whether the patient had developed MRONJ at the extraction site at 6 months. The secondary evaluation outcome was whether the extraction socket mucosa healed completely within 1 month. Statistical analysis included Chi-square, Fisher’s exact, Mann–Whitney U/t tests and survival analysis to contrast between LDA and HDA group. Significance was set at p ≤ 0.05. Results: A total of 82 extraction sites in 51 patients (31 females in LDA group with a mean age of 66.58 ± 13.29 years. 14 females and 6 males in HDA group with a mean age of 58.24 ± 11.63 years) were included in the study. Of these, 47 extraction sites in the LDA group, 35 extraction sites in the HDA group. During postoperative follow-up, MRONJ only occurred in 2 extraction sites in HDA group in two patients, resulting in a postoperative clinical healing rate of 100% (47/47) in LDA group and 94.3% (33/35) in HDA group. A significant difference in the time to extraction socket mucosal healing was observed between the LDA and HDA groups ( p ≤ 0.05). Conclusions: This study demonstrated that in patients with potential risks of MRONJ, the application of mucoperiosteal flap combined with perforation technique based teeth extraction method could safely and effectively alleviate the dental inflammation in the oral cavity, and mitigates the risk of MRONJ development.