Silk fibroin-chondroitin sulfate scaffold with immuno-inhibition property for articular cartilage repair
Silk fibroin-chondroitin sulfate scaffold with immuno-inhibition property for articular cartilage repair
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具有免疫抑制特性的丝素蛋白-硫酸软骨素支架用于关节软骨修复
DOI：
10.1016/j.actbio.2017.09.005
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发表时间：
2017
影响因子：
9.7
通讯作者：
Ouyang Hong Wei
中科院分区：
文献类型：
--
作者：
Zhou Feifei;Zhang Xianzhu;Cai D;an;Li Jun;Mu Qin;Zhang Wei;Zhu Shouan;Jiang Yangzi;Shen Weiliang;Zhang Shufang;Ouyang Hong Wei
随着软骨组织工程的兴起，对良好支架材料的需求日益增加。硫酸软骨素（CS）和丝素蛋白作为组织工程支架材料具有良好的生物相容性和安全性。然而，纯CS支架的快速降解速率对有效地重建类似于天然关节软骨的新组织提出了挑战。同时丝素蛋白因其优异的力学性能、持久的抗活体损伤和免疫功能低下等优点而被广泛用作结构组成材料。复合丝素蛋白和CS支架在关节软骨修复中的应用还没有得到很好的研究。在这里，我们报告，丝素蛋白和CS的组合可以协同促进关节软骨缺损修复。采用盐析法、冷冻干燥法和交联法制备了丝素蛋白（silk）和丝素蛋白/壳聚糖（silk-CS）支架。通过体外细胞粘附、增殖和迁移实验，研究了支架材料的生物相容性。我们发现silk-CS支架比silk支架保持了更好的软骨细胞表型;此外，silk-CS支架减少了由白细胞介素（IL）-1β诱导的软骨细胞炎症反应，这与CS的抗炎活性一致。用兔骨软骨缺损模型评价其在体软骨修复情况。在ICRS组织学评价中，在植入6周和12周后，丝-CS支架比丝支架诱导更多的新组织形成和更好的结构恢复。总之，我们已经开发了一种用于软骨组织工程的丝素蛋白/硫酸软骨素支架，其具有免疫抑制特性并且可以提高软骨的自我修复能力。目前的支架通常集中于提供足够的机械支撑或仿生结构以促进软骨修复。因此，丝绸被广泛采用和研究。然而，炎症是OA最重要的因素之一。但很少有软骨修复支架材料具有抗炎特性的报道。同时，硫酸软骨素（CS）是存在于天然软骨ECM中的糖胺聚糖，并表现出许多有用的生物学特性，包括抗炎活性。因此，我们设计了这种蚕丝-CS支架，并证明该支架在体外和体内均表现出良好的抗炎作用，在动物模型中促进了关节软骨缺损的修复。
The demand of favorable scaffolds has increased for the emerging cartilage tissue engineering. Chondroitin sulfate (CS) and silk fibroin have been investigated and reported with safety and excellent biocompatibility as tissue engineering scaffolds. However, the rapid degradation rate of pure CS scaffolds presents a challenge to effectively recreate neo-tissue similar to natural articular cartilage. Meanwhile the silk fibroin is well used as a structural constituent material because its remarkable mechanical properties, long-lastingin vivostability and hypoimmunity. The application of composite silk fibroin and CS scaffolds for joint cartilage repair has not been well studied. Here we report that the combination of silk fibroin and CS could synergistically promote articular cartilage defect repair. The silk fibroin (silk) and silk fibroin/CS (silk-CS) scaffolds were fabricated with salt-leaching, freeze-drying and crosslinking methodologies. The biocompatibility of the scaffolds was investigatedin vitroby cell adhesion, proliferation and migration with human articular chondrocytes. We found that silk-CS scaffold maintained better chondrocyte phenotype than silk scaffold; moreover, the silk-CS scaffolds reduced chondrocyte inflammatory response that was induced by interleukin (IL)-1β, which is in consistent with the well-documented anti-inflammatory activities of CS. Thein vivocartilage repair was evaluated with a rabbit osteochondral defect model. Silk-CS scaffold induced more neo-tissue formation and better structural restoration than silk scaffold after 6 and 12 weeks of implantation in ICRS histological evaluations. In conclusion, we have developed a silk fibroin/ chondroitin sulfate scaffold for cartilage tissue engineering that exhibits immuno-inhibition property and can improve the self-repair capacity of cartilage.Statement of SignificanceSevere cartilage defect such as osteoarthritis (OA) is difficult to self-repair because of its avascular, aneural and alymphatic nature. Current scaffolds often focus on providing sufficient mechanical support or bio-mimetic structure to promote cartilage repair. Thus, silk has been adopted and investigated broadly. However, inflammation is one of the most important factors in OA. But few scaffolds for cartilage repair reported anti-inflammation property. Meanwhile, chondroitin sulfate (CS) is a glycosaminoglycan present in the natural cartilage ECM, and has exhibited a number of useful biological properties including anti-inflammatory activity. Thus, we designed this silk-CS scaffold and proved that this scaffold exhibited good anti-inflammatory effects bothin vitroandin vivo, promoted the repair of articular cartilage defect in animal model.