用于模拟细胞外基质的硫醇-烯水凝胶的制备

Preparation of Thiol-ene Hydrogels for Extracellular Matrix Simulation

先使四臂末端羟基化的聚乙二醇(4-PEG-OH)与降冰片烯(NB)反应制备4-PEG-NB大分子单体,然后将其与二硫苏糖醇通过‘硫醇-烯点击化学方法逐步生长式’制备出硬度可调节的水凝胶并辅以REDV生物多肽修饰,用于模拟二维(2D)和三维(3D)细胞外基质(ECM)。结果表明,4-PEG-NB单体合成的接枝率为90%,制备出的硫醇-烯水凝胶具有多孔结构,发生了硫醇-烯交联反应且交联度高;改变交联比例可将杨氏模量分别调控为0.79、2.40、4.52 kPa;随着水凝胶交联比例的提高,孔隙率随之提高而溶胀率降低。这种水凝胶具有体外降解性;药物释放的前期速度较高,后期较低。2D和3D ECM模拟的细胞培养结果表明,这种水凝胶具有优异的生物相容性。

The tunable stiffness step-growth hydrogels were prepared by thiol-ene click chemistry between 4 arm-polyethylene glycol-norbornene(4-PEG-NB)and dithiothreitol and supplemented with REDV biopeptide modification for 2D and 3D extracellular matrix(ECM)simulations,in which the 4-PEGNB macromonomer was produced by the reaction of 4-PEG-OH with norbornene.The results show that the prepared thiol-ene hydrogels present a porous structure,and the thiol-ene cross-linking reaction with high cross-linking efficiency was also confirmed.The tunable Young’s modulus of hydrogels could be precisely regulated to 0.79,2.40,and 4.52 k Pa by changing the thiol-ene ratio.As the crosslink ratio of the hydrogels increased,the porosity gradually increased and the swelling rate gradually decreased.The drug release of the hydrogels was faster in the early stage and then gradually slowed down.The cell culture results of 2 D and 3 D ECM simulations show that the hydrogel had excellent biocompatibility.