3D bioprinting mesenchymal stem cell-laden construct with core–shell nanospheres for cartilage tissue engineering
3D bioprinting mesenchymal stem cell-laden construct with core–shell nanospheres for cartilage tissue engineering
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DOI：
10.1088/1361-6528/aaafa1
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发表时间：
2018-03
期刊：
影响因子：
3.5
通讯作者：
Wei Zhu;H. Cui;Benchaa Boualam;F. Masood;Erin P. Flynn;Raj Rao;Zhi-Yong Zhang;Lijie Grace Zhang
中科院分区：
文献类型：
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作者：
Wei Zhu;H. Cui;Benchaa Boualam;F. Masood;Erin P. Flynn;Raj Rao;Zhi-Yong Zhang;Lijie Grace Zhang
软骨组织易于降解，并且由于其无血管性而几乎没有自我愈合的能力。组织工程是一种新型的软骨修复方法，它为损伤组织的修复提供了人工支架。3D生物打印通过同时整合活细胞、生物材料和生物线索来提供定制的支架，为修复退行性组织提供了更大的潜力。在细胞选择方面，间充质干细胞（MSC）具有很强的分化成各种细胞类型的能力，包括软骨细胞，因此可以用作3D生物打印中的软骨细胞来源。在本研究中，我们利用桌面立体光刻为基础的3D生物打印机的一种新的细胞负载软骨组织构建制造。可打印树脂由10%明胶甲基丙烯酸酯（GelMA）基质、各种浓度的聚乙二醇二丙烯酸酯（PEGDA）、生物相容性光引发剂和通过核-壳电喷雾技术制备的转化生长因子β 1（TGF-β1）包埋纳米球组成。我们发现，在GelMA水凝胶中加入PEGDA大大提高了打印分辨率。压缩测试表明，生物打印支架的模量成比例地增加与PEGDA的浓度，而溶胀比随着PEGDA浓度的增加而降低。共聚焦显微镜图像说明细胞和纳米球均匀地分布在整个生物打印的构建体中。在5%/10%（PEGDA/GelMA）水凝胶上生长的细胞呈现最高的细胞活力和增殖速率。TGF-β1包埋于纳米微球中，可持续释放21 d，促进MSCs向软骨细胞的分化。含有TGF-β1的纳米球的载有细胞的生物打印软骨构建体是软骨再生的有前途的策略。
Cartilage tissue is prone to degradation and has little capacity for self-healing due to its avascularity. Tissue engineering, which provides artificial scaffolds to repair injured tissues, is a novel and promising strategy for cartilage repair. 3D bioprinting offers even greater potential for repairing degenerative tissue by simultaneously integrating living cells, biomaterials, and biological cues to provide a customized scaffold. With regard to cell selection, mesenchymal stem cells (MSCs) hold great capacity for differentiating into a variety of cell types, including chondrocytes, and could therefore be utilized as a cartilage cell source in 3D bioprinting. In the present study, we utilize a tabletop stereolithography-based 3D bioprinter for a novel cell-laden cartilage tissue construct fabrication. Printable resin is composed of 10% gelatin methacrylate (GelMA) base, various concentrations of polyethylene glycol diacrylate (PEGDA), biocompatible photoinitiator, and transforming growth factor beta 1 (TGF-β1) embedded nanospheres fabricated via a core–shell electrospraying technique. We find that the addition of PEGDA into GelMA hydrogel greatly improves the printing resolution. Compressive testing shows that modulus of the bioprinted scaffolds proportionally increases with the concentrations of PEGDA, while swelling ratio decreases with the increase of PEGDA concentration. Confocal microscopy images illustrate that the cells and nanospheres are evenly distributed throughout the entire bioprinted construct. Cells grown on 5%/10% (PEGDA/GelMA) hydrogel present the highest cell viability and proliferation rate. The TGF-β1 embedded in nanospheres can keep a sustained release up to 21 d and improve chondrogenic differentiation of encapsulated MSCs. The cell-laden bioprinted cartilage constructs with TGF-β1-containing nanospheres is a promising strategy for cartilage regeneration.