Sustained Release SDF-1α/TGF-β1-Loaded Silk Fibroin-Porous Gelatin Scaffold Promotes Cartilage Repair
Sustained Release SDF-1α/TGF-β1-Loaded Silk Fibroin-Porous Gelatin Scaffold Promotes Cartilage Repair
复制标题
缓释 SDF-1 α/TGF-β 1 负载丝素蛋白多孔明胶支架促进软骨修复
DOI：
10.1021/acsami.9b01532
复制
发表时间：
2019-04-24
影响因子：
9.5
通讯作者：
Zha, Zhengang
中科院分区：
文献类型：
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作者：
Chen, Yuanfeng;Wu, Tingting;Zha, Zhengang
持续向损伤部位输送生长因子对于为软骨损伤修复创造有利的微环境至关重要。在本研究中，我们制备了一种新型的缓释支架，基质衍生因子-1 α（SDF-1 α）/转化生长因子-β 1（TGF-β 1）负载的丝素蛋白-多孔明胶支架（GSTS）。GSTS持续释放SDF-1 α和TGF-β 1，通过促进细胞归巢和软骨分化来增强软骨修复。扫描电子显微镜显示GSTS是多孔微结构，蛋白质释放测定证明SDF-1 α和TGF-β 1从GSTS持续释放。骨髓间充质干细胞（MSCs）接种于GSTS后，在体外仍保持较高的细胞活性和良好的细胞分布及表型。此外，MSC在负载TGF-β 1的支架（GSTS或GST：仅负载TGF-β 1）中获得增强的软骨分化能力，并且来自负载SDF-1 α的支架（GSTS或GSS：仅负载SDF-1 α）的条件培养基有效地促进MSC迁移。将GSTS移植于大鼠膝关节骨软骨缺损处，12周后可促进软骨再生，修复软骨缺损。我们的研究表明，GSTS可以促进体外MSC归巢、迁移、软骨分化，并且SDF-1 α和TGF-β 1对促进体内软骨形成具有协同作用。这种释放SDF-1 α和TGF-β 1的GSTS在软骨修复中具有很好的治疗潜力。
Continuous delivery of growth factors to the injury site is crucial to creating a favorable microenvironment for cartilage injury repair. In the present study, we fabricated a novel sustained-release scaffold, stromal-derived factor-1 alpha (SDF-1 alpha)/transforming growth factor-beta 1 (TGF-beta 1)-loaded silk fibroin-porous gelatin scaffold (GSTS). GSTS persistently releases SDF-1 alpha and TGF-beta 1, which enhance cartilage repair by facilitating cell homing and chondrogenic differentiation. Scanning electron microscopy showed that GSTS is a porous microstructure and the protein release assay demonstrated the sustainable release of SDF-1 alpha and TGF-beta 1 from GSTS. Bone marrow-derived mesenchymal stem cells (MSCs) maintain high in vitro cell activity and excellent cell distribution and phenotype after seeding into GSTS. Furthermore, MSCs acquired enhanced chondrogenic differentiation capability in the TGF-beta 1-loaded scaffolds (GSTS or GST: loading TGF-beta 1 only) and the conditioned medium from SDF-1 alpha-loaded scaffolds (GSTS or GSS: loading SDF-1 alpha only) effectively promoted MSCs migration. GSTS was transplanted into the osteochondral defects in the knee joint of rats, and it could promote cartilage regeneration and repair the cartilage defects at 12 weeks after transplantation. Our study shows that GSTS can facilitate in vitro MSCs homing, migration, chondrogenic differentiation and SDF-1 alpha and TGF-beta 1 have a synergistic effect on the promotion of in vivo cartilage forming. This SDF-1 alpha and TGF-beta 1 releasing GSTS have promising therapeutic potential in cartilage repair.