Xiao Fei, Shi Jingjing, Zhang Xinhai, Hu Min, Chen Kangming, Shen Chao, Chen Xiaodong, Guo Yaping, Li Yang
Department of Orthopedic Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai, China.
The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai, China.
Front Bioeng Biotechnol. 2023 Feb 15;11:1071692. doi: 10.3389/fbioe.2023.1071692. eCollection 2023.
Reducing the incidence of bone defects caused by trauma and other primary diseases is an urgent task in modern society. In the present study, we developed a gadolinium-doped whitlockite/chitosan (Gd-WH/CS) scaffold and assessed its biocompatibility, osteoinductivity, and bone regeneration capacity for the treatment of calvarial defect in a Sprague-Dawley (SD) rat model. The Gd-WH/CS scaffolds possessed a macroporous structure, with a pore size ranging 200-300 μm, which facilitated the growth of bone precursor cells and tissues into scaffold. Results of cytological and histological biosafety experiments showed that both WH/CS and Gd-WH/CS scaffolds were non-cytotoxic to human adipose-derived stromal cells (hADSCs) and bone tissue, which demonstrated the excellent biocompatibility of Gd-WH/CS scaffolds. Results of western blotting and real-time PCR analysis provided a possible mechanism that Gd ions in the Gd-WH/CS scaffolds promoted the osteogenic differentiation of hADSCs through the GSK3β/β-catenin signaling pathway and significantly upregulated the expression of osteogenic related genes (OCN, OSX and COL1A1). Finally, in animal experiments, SD rat cranial defects were effectively treated and repaired with Gd-WH/CS scaffolds due to its appropriate degradation rate and excellent osteogenic activity. This study suggests the potential utility of the Gd-WH/CS composite scaffolds in treating bone defect disease.
减少由创伤和其他原发性疾病引起的骨缺损发生率是现代社会的一项紧迫任务。在本研究中，我们制备了钆掺杂的白磷钙石/壳聚糖（Gd-WH/CS）支架，并在Sprague-Dawley（SD）大鼠颅骨缺损模型中评估了其生物相容性、骨诱导性和骨再生能力。Gd-WH/CS支架具有大孔结构，孔径范围为200-300μm，这有利于骨前体细胞和组织在支架内生长。细胞学和组织学生物安全性实验结果表明，WH/CS和Gd-WH/CS支架对人脂肪来源的基质细胞（hADSCs）和骨组织均无细胞毒性，这证明了Gd-WH/CS支架具有优异的生物相容性。蛋白质免疫印迹和实时定量PCR分析结果提供了一种可能的机制，即Gd-WH/CS支架中的钆离子通过GSK3β/β-连环蛋白信号通路促进hADSCs的成骨分化，并显著上调成骨相关基因（OCN、OSX和COL1A1）的表达。最后，在动物实验中，由于Gd-WH/CS支架具有合适的降解速率和优异的成骨活性，有效地治疗和修复了SD大鼠颅骨缺损。本研究表明Gd-WH/CS复合支架在治疗骨缺损疾病方面具有潜在应用价值。
