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Protein-reactive nanofibrils decorated with cartilage-derived decellularized extracellular matrix for osteochondral defects.
Biomaterials ( IF 12.8 ) Pub Date : 2020-06-27 , DOI: 10.1016/j.biomaterials.2020.120214
Hye Sung Kim 1 , Nandin Mandakhbayar 2 , Hae-Won Kim 3 , Kam W Leong 4 , Hyuk Sang Yoo 5
Affiliation  

Cartilage defect is difficult to heal due to its avascular properties. Implantation of mesenchymal stem cell is one of the most promising approach for regenerating cartilage defects. Here we prepared polymeric nanofibrils decorated with cartilage-derived decellularized extracellular matrix (dECM) as a chondroinductive scaffold material for cartilage repair. To fabricate nanofibrils, eletrospun PCL nanofibers were fragmented by subsequent mechanical and chemical process. The nanofibrils were surface-modified with poly(glycidyl methacrylate) (PGMA@NF) via surface-initiated atom transfer radical polymerization (SI-ATRP). The epoxy groups of PGMA@NF were subsequently reacted with dECM prepared from bovine articular cartilage. Therefore, the cartilage-dECM-decorated nanofibrils structurally and biochemically mimic cartilage-specific microenvironment. Once adipose-derived stem cells (ADSCs) were self-assembled with the cartilage-dECM-decorated nanofibrils by cell-directed association, they exhibited differentiation hallmarks of chondrogenesis without additional biologic additives. ADSCs in the nanofibril composites significantly increased expression of chondrogenic gene markers in comparison to those in pellet culture. Furthermore, ADSC-laden nanofibril composites filled the osteochondral defects compactly due to their clay-like texture. Thus, the ADSC-laden nanofibril composites supported the long-term regeneration of 12 weeks without matrix loss during joint movement. The defects treated with the ADSC-laden PGMA@NF significantly facilitated reconstruction of their cartilage and subchondral bone ECM matrices compared to those with ADSC-laden nanofibrils, non-specifically adsorbing cartilage-dECM without surface decoration of PGMA.



中文翻译:

具有软骨源性脱细胞细胞外基质修饰的蛋白反应性纳米原纤维,用于软骨软骨缺损。

软骨缺损由于其无血管特性而难以治愈。间充质干细胞的植入是再生软骨缺损最有前途的方法之一。在这里,我们准备了由软骨衍生的脱细胞细胞外基质(dECM)装饰的聚合物纳米原纤维,作为软骨修复的软骨诱导支架材料。为了制造纳米原纤维,通过后续的机械和化学工艺将静电纺PCL纳米纤维破碎。通过聚甲基丙烯酸缩水甘油酯(PGMA @ NF)对纳米原纤维进行表面改性表面引发的原子转移自由基聚合(SI-ATRP)。PGMA @ NF的环氧基随后与由牛关节软骨制备的dECM反应。因此,用软骨-dECM修饰的纳米原纤维在结构和生化上模拟了特定于软骨的微环境。一旦脂肪干细胞(ADSC)通过细胞定向结合与软骨修饰的ECM修饰的纳米原纤维自组装,它们就显示出软骨形成的分化特征,而无需其他生物添加剂。与粒状培养物中的那些相比,纳米原纤维复合物中的ADSCs显着增加了软骨生成基因标志物的表达。此外,由于ADSC负载的纳米原纤维复合材料具有粘土状质地,因此可以紧凑地填充骨软骨缺损。从而,载有ADSC的纳米原纤维复合材料支持12周的长期再生,并且关节运动期间不会损失基质。与载有ADSC的纳米纤维,无特异性吸附软骨的dECM相比,ADSC载有PGMA @ NF的缺陷明显促进了软骨和软骨下骨ECM基质的重建。

更新日期:2020-06-27
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