Guo Ting, Lim Casey, Noshin Maeesha, Ringel Julia P, Fisher John P
Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.
Center for Engineering Complex Tissues, University of Maryland, College Park, MD, USA.
Bioprinting. 2018 Jun;10. doi: 10.1016/j.bprint.2018.e00038. Epub 2018 Nov 8.
Present bioprinting techniques lack the methodology to print with bioactive materials that retain their biological functionalities. This constraint is due to the fact that extrusion-based printing of synthetic polymers is commonly performed at very high temperatures in order to achieve desired mechanical properties and printing resolutions. Consequently, current methodology prevents printing scaffolds embedded with bioactive molecules, such as growth factors. With the wide use of mesenchymal stem cells (MSCs) in regenerative medicine research, the integration of growth factors into 3D printed scaffolds is critical because it can allow for inducible MSC differentiation. We have successfully incorporated growth factors into extrusion printed poly (lactic-co-glycolic acid) (PLGA) scaffolds by introducing dimethyl sulfoxide (DMSO) for low temperature printing. Mechanical testing results demonstrated significantly different compressive and tensile properties for PLGA scaffold printed with or without DMSO. In particular, the PLGA-DMSO scaffold displayed a highly stretchable feature compared to the regular PLGA scaffold. The cellular response of growth factor introduction was evaluated using human mesenchymal stem cells (hMSCs). By evaporating the DMSO after printing, we ensured that there was no cytotoxic effect on seeded hMSCs. The addition of lineage specific growth factors led to increased expression of corresponding genetic markers for chondrogenesis, osteogenesis, and adipogenesis. We concluded that the use of DMSO for 3D printed scaffold fabrication with bioactive items is a revolutionary methodology in advancing regenerative medicine. The incorporation of bioactive molecules opens pathways to more therapeutic uses for 3D printing in treating damaged or deteriorating native tissue.
目前的生物打印技术缺乏使用能保持其生物功能的生物活性材料进行打印的方法。这种限制是由于基于挤出的合成聚合物打印通常在非常高的温度下进行,以实现所需的机械性能和打印分辨率。因此,当前的方法阻碍了打印嵌入生物活性分子(如生长因子)的支架。随着间充质干细胞(MSCs)在再生医学研究中的广泛应用,将生长因子整合到3D打印支架中至关重要,因为这可以诱导MSCs分化。我们通过引入二甲基亚砜(DMSO)进行低温打印,成功地将生长因子整合到挤出打印的聚(乳酸-乙醇酸)(PLGA)支架中。力学测试结果表明,添加或不添加DMSO打印的PLGA支架的压缩和拉伸性能存在显著差异。特别是,与常规PLGA支架相比,PLGA-DMSO支架具有高度可拉伸的特性。使用人间充质干细胞(hMSCs)评估了生长因子引入后的细胞反应。通过在打印后蒸发DMSO,我们确保了对接种的hMSCs没有细胞毒性作用。添加谱系特异性生长因子导致软骨生成、骨生成和脂肪生成的相应基因标记物表达增加。我们得出结论,使用DMSO进行具有生物活性物品的3D打印支架制造是推进再生医学的一种革命性方法。生物活性分子的整合为3D打印在治疗受损或退化的天然组织方面开辟了更多治疗用途的途径。