3D-bioprinting a genetically inspired cartilage scaffold with GDF5-conjugated BMSC-laden hydrogel and polymer for cartilage repair
3D-bioprinting a genetically inspired cartilage scaffold with GDF5-conjugated BMSC-laden hydrogel and polymer for cartilage repair
复制标题
使用 GDF5 缀合的 BMSC 水凝胶和聚合物 3D 生物打印用于软骨修复的遗传软骨支架
DOI：
10.7150/thno.38061
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发表时间：
2019-01-01
期刊：
影响因子：
12.4
通讯作者：
Dai, Kerong
中科院分区：
文献类型：
--
作者：
Sun, Ye;You, Yongqing;Dai, Kerong
理论基础：关节软骨损伤在先天性关节发育不良患者中非常常见。遗传学研究已经证实，生长分化因子5(GDF5)是不同人群中关节发育不良和骨关节炎进展的共同基因。然而，将GDF5应用于关节软骨的生物再生修复的研究很少。方法与结果：在本研究中，我们报告了GDF5基因座与髋关节发育不良的遗传关联。在不同群体中进行的GWAs和复制研究获得了GDF5基因座的显著信号。GDF5在DDH兔髋关节软骨中的表达随等位基因的差异而失调，在兔软骨缺损模型修复后的软骨中表达上调。GDF5在体外促进骨髓干细胞(BMSCs)的软骨形成和迁移，在裸鼠体内用GDF5诱导BMSCs异位软骨生成。受基因启发，我们通过3D生物打印GDF5结合的骨髓间充质干细胞支架，进一步产生了用于软骨修复的功能性膝关节软骨构建。GDF5复合支架的软骨修复效果明显好于对照组。同时，将3D生物打印的GDF5-BMSC支架移植到兔膝上，获得了长期的软骨保护。结论：综上所述，我们的研究结果证实了GDF5和DDH之间的遗传关联，这进一步激发了我们创造一种可植入的GDF5连接的BMSC支架，并通过一步3D生物打印用于软骨修复。
Rationale: Articular cartilage injury is extremely common in congenital joint dysplasia patients. Genetic studies have identified Growth differentiation factor 5 (GDF5) as a shared gene in joint dysplasia and OA progression across different populations. However, few studies have employed GDF5 in biological regeneration for articular cartilage repair. Methods & Results: In the present study, we report identified genetic association between GDF5 loci and hip joint dysplasia with genome-wide association study (GWAS). GWAS and replication studies in separate populations achieved significant signals for GDF5 loci. GDF5 expression was dysregulated with allelic differences in hip cartilage of DDH and upregulated in the repaired cartilage in a rabbit cartilage defect model. GDF5 in vitro enhanced chondrogenesis and migration of bone marrow stem cells (BMSCs), GDF5 was tested in ectopic cartilage generation with BMSCs by GDF5 in nude mice in vivo. Genetically inspired, we further generated functional knee articular cartilage construct for cartilage repair by 3d-bioprinting a GDF5-conjugated BMSC-laden scaffold. GDF5-conjugated scaffold showed better cartilage repairing effects compared to control. Meanwhile, transplantation of the 3D-bioprinted GDF5-conjugated BMSC-laden scaffold in rabbit knees conferred long-term chondroprotection. Conclusions: In conclusion, we report identified genetic association between GDF5 and DDH with combined GWAS and replications, which further inspired us to generate a ready-to-implant GDF5-conjugated BMSC-laden scaffold with one-step 3d-bioprinting for cartilage repair.