To design and prepare a novel controlled release system for sustained release of two drugs. In this study, a double-layer microsphere was incorporated with strontium-doped calcium polyphosphate (SCPP) scaffold to facilitate bone regeneration and achieve skull repair. The double-layer microsphere combining tetracycline loaded sodium alginate and matrix metalloproteinase-2 (MMP-2) loaded chitosan was manufactured by electrospinning, which were further adhered to SCPP scaffold. The characteristics of microstructure were observed through scanning electron microscope. Loading efficiencies and the optimal ratio of microsphere of the obtained controlled release system were investigated. In addition, the cytotoxicity and the effects on osteoblast proliferation and expressions of osteogenesis-related factors were examined in vitro. Thereafter, the compound material with the controlled release system was implanted in the skull defect of rabbit to evaluate its properties of promoting bone regeneration. The results indicated that this novel controlled release system with SCPP scaffold and the double-layer microspheres loaded with tetracycline and MMP-2 could be a promising material for bones repair.
Meningiomas are benign tumors that originate from the meningothelial arachnoid cells, but they rarely develop extracranially. There is no specific surgical guideline for resecting them in the maxillary sinus, and little is known about their biological behavior and operative management.We present a 54-year-old female patient referred to our department with a primary extracranial meningioma that presented as buccal swelling associated with headache. On clinical examination the mass was non-tender, fixed, sessile and non-pulsatile situating in the right maxillary sinus. Computed tomography scan showed a well-defined mass of 7 cm × 6 cm × 6 cm compressing the surrounding structures. Magnetic resonance imaging revealed a well circumscribed heterogenous lesion with necrotic center and relatively hypointense on T2-weighted imaging. Imaging studies revealed no evidence of intracranial extension and metastatic nests. Biopsy showed grade I primary extracranial with low mitotic activity. Total maxillectomy with excision of tumor and adjacent paranasal structures following reconstruction of the orbit and maxilla with tissue patch was done by the maxillofacial surgeon. The biopsy reported fibrous meningioma based on the hematoxylin and eosin section. On immunohistochemistry the tumor cells were positive for vimentin, focally positive for epithelial membrane antigen and CD99 and negative for signal transducer and activator of transcription 6. The mass was removed surgically with reconstruction, and the pathological studies confirmed the diagnosis to be an extracranial meningioma. The present study briefly reviews the current knowledge concerning the diagnosis and treatment of extracranial meningiomas in the head and neck area and offers suggestions for managing extracranial meningiomas in the paranasal sinuses.To conclude, extracranial meningiomas in the paranasal sinuses may be successfully managed by surgical treatment without evident post-surgery complications.
Abstract Delayed graft function (DGF) is a severe complication following kidney transplantation, and currently, there is a lack of accurate prediction tools tailored for the Chinese population. This study integrates data from 1,093 kidney transplant cases across four medical centers in China (2016–2024) to develop and validate a machine learning-based model for DGF prediction. By comparing nine machine learning algorithms, we found that the LightGBM model performed best in external validation (AUC = 0.80, accuracy = 0.73). SHAP analysis identified donor GFR, donor hemoglobin, and recipient plasma BNP levels as the primary predictive factors, while also highlighting novel predictors such as donor microscopic hematuria and APTT. Cox regression analysis showed that preoperative dialysis duration in recipients (HR = 1.006, 95% CI: 1.001–1.012) was an independent predictor of DGF recovery. In the follow-up study, we observed that while the DGF mortality group exhibited the most significant kidney function impairment (serum creatinine β = 200.57, eGFR β = -39.91), the prognosis of the DGF survival group was comparable to that of the non-DGF survival group. Additionally, the duration of DGF (16.66 ± 13.73 vs. 15.44 ± 14.62 days) and the number of dialysis treatments (8.13 ± 7.39 vs. 7.78 ± 7.22 sessions) were not significantly associated with prognosis. Based on these findings, we developed an online prediction platform (www.kidney-dgf-match.cn) to support clinical decision-making. This study not only establishes the first high-precision DGF prediction model for the Chinese population but also reveals the potential for favorable outcomes in DGF patients with proper management, offering new insights for optimizing post-transplant management strategies.
Blood and lymphatic vessels form a versatile transport network and provide inductive signals to regulate tissue-specific functions. Blood vessels in bone regulate osteogenesis and hematopoiesis, but current dogma suggests that bone lacks lymphatic vessels. Here, by combining high-resolution light-sheet imaging and cell-specific mouse genetics, we demonstrate presence of lymphatic vessels in mouse and human bones. We find that lymphatic vessels in bone expand during genotoxic stress. VEGF-C/VEGFR-3 signaling and genotoxic stress-induced IL6 drive lymphangiogenesis in bones. During lymphangiogenesis, secretion of CXCL12 from proliferating lymphatic endothelial cells is critical for hematopoietic and bone regeneration. Moreover, lymphangiocrine CXCL12 triggers expansion of mature Myh11+ CXCR4+ pericytes, which differentiate into bone cells and contribute to bone and hematopoietic regeneration. In aged animals, such expansion of lymphatic vessels and Myh11-positive cells in response to genotoxic stress is impaired. These data suggest lymphangiogenesis as a therapeutic avenue to stimulate hematopoietic and bone regeneration.
Calcium polyphosphate (CPP) is a novel bioceramic bone substitute, which is favored because its composition is highly similar to natural bone. According to previous studies, doping ions into CPP is an effective and convenient method for overcoming the shortcomings, such as poor osteoconductivity of CPP. Lithium (Li) is a fairly new additive to bone substitutes that brought attention due to its role in osteogenesis. The present study was conducted to assess whether doping Li into CPP could influence the microstructure, degradation, and osteoinductivity of CPP. The results found that both CPP and Li-doped CPP (LiCPP) had a single beta-CPP phase, indicating that Li did not affect the crystallized phase. SEM images revealed that both scaffolds were porous, while the surface of LiCPP was rougher and more uneven compared to CPP. Also, a better degradation property of LiCPP was observed via weight loss and ion release tests. In vitro study found that LiCPP extracts had advantages of promoting osteoblasts' proliferation and differentiation over CPP extracts. In vivo study on rabbit's cranial defects was also conducted. Microcomputed tomography and histological staining showed that LiCPP had better osteoconductivity than CPP. This study proved that doping Li into CPP is a feasible modification method, and LiCPP might be a suitable bioceramic for bone tissue engineering.
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