文献：Methacrylated pullulan/polyethylene (glycol) diacrylate composite hydrogel for cartilage tissue engineering

文献链接：https://www.tandfonline.com/doi/abs/10.1080/09205063.2021.1899888

作者：Xiaoping Qin, Rui He, Hao Chen, Dejie Fu, Yang Peng, Shuo Meng, Cheng，Chen & Liu Yang

相关产品：Pullulan（普鲁兰多糖）

原文摘要：

Pullulan hydrogels are widely used in tissue engineering and drug delivery. However, these hydrogels do not meet the requirements of articular cartilage repair because of their fast degradation rate and poor mechanical strength. Herein, we fabricated a hybrid hydrogel system by combining pullulan with synthetic polymers polyethylene (glycol) diacrylate (PEGDA). In this study, pullulan was modified with methacrylic anhydride (MA) to obtain photocrosslinkable methacrylated pullulan (PulMA). Moreover, the lithium phenyl(2,4,6-trimethylbenzoyl)phosphinate (LAP) was used as a water-soluble UV photoinitiator to form the PulMA/PEGDA hydrogel by photopolymerization strategy. Compared with the pure PulMA hydrogel, the increase of PEGDA concentration led to a slower degradation rate and an increase of residual mass from 63.9% to 86.8%. There was about 8-fold increase in storage modulus (G0) (reach to 16.0  103 Pa) and 13-fold increase in compressive modulus (reach to 1.17 ± 0.17 MPa) with increasing the concentration of PEGDA to 15% (w/v) in the hydrogel. In cell culture in vitro, the rabbit’s mesenchymal stem cells (MSCs) encapsulated in the PulMA/PEGDA hydrogel could adhere and proliferate,indicating that the PulMA/PEGDA hydrogel had a good biocompatibility. Furthermore, the hydrogels supported glycosaminoglycan (GAG) synthesis, and chondrogenic phenotype of MSCs with TGF-b3-containing chondrogenic medium. This study demonstrated that the photo-crosslinking PulMA/PEGDA hydrogels, with good mechanical properties and slow degradation rate are promising scaffolds for cartilage repair and regeneration.

Pullulan 是一种天然多糖，也被称为普鲁兰多糖。它是由出芽短梗霉（Aureobasidium pullulans）发酵产生的。其化学结构是由麦芽三糖（由三个葡萄糖单元组成）通过 α - 1,6 - 糖苷键连接而成的线性聚合物。这种结构使得 pullulan 具有一些性质，例如它具有良好的水溶性，在水中能够形成透明、无味、无臭的溶液。由于它是线性聚合物，分子链相对较为规整，没有像一些支化多糖那样复杂的空间结构。基于Pullulan的性能，PulMA/PEGDA水凝胶的合成路线如下：

图：合成示意

PulMA合成：

将普鲁兰溶解在PBS中溶解。然后，将PBS中的MA滴加入普鲁兰溶液中。混合溶液在室温下连续搅拌，用氢氧化钠调节保持溶液的pH值，然后用超纯水透析。所得到的普鲁兰衍生物（PulMA）通过冷冻干燥获得，并在4℃下保存以供进一步使用。

PulMA/PEGDA水凝胶的制备：

将PulMA溶解在超纯水中，并将PEGDA加入到浓度不同的溶液中。将LAP溶液以一定的体积比加入到PulMA/PEGDA的混合溶液中。然后，将混合溶液加入紫外光下暴露。按照相同的方法分别制备了PulMA和PEGDA水凝胶。

图：核磁图像

结论：

该文献成功制备了基于Pullulan合成的PulMA/PEGDA水凝胶，这是用紫外光交联法制备的一种新型生物相容性的水凝胶。PulMA/PEGDA水凝胶具有细胞相容性，能够支持GAG的合成，并对MSCs的软骨生成表型有有益的影响。综上，PulMA/PEGDA水凝胶系统有良好的力学性能和较慢的降解速率，在软骨修复和再生方面具有应用潜力。