Zant Erwin, Grijpma Dirk W
MIRA Institute for Biomedical Technology and Technical Medicine and Department of Biomaterials Science and Technology, University of Twente , P.O. Box 217, 7500 AE Enschede, The Netherlands.
W. J. Kolff Institute, Department of Biomedical Engineering, University of Groningen, University Medical Centre Groningen , P.O. Box 196, 9700 AD Groningen, The Netherlands.
Biomacromolecules. 2016 May 9;17(5):1582-92. doi: 10.1021/acs.biomac.5b01721. Epub 2016 Apr 25.
Major drawbacks of synthetic hydrogels are their poor mechanical properties and their limited ability to allow cell attachment and proliferation. By photo-cross-linking mixtures of dimethacrylate-functionalized oligomers (macromers) in a combinatorial manner in solution, synthetic hydrogels with high water uptake and the remarkable ability to promote cell adhesion and proliferation were prepared. A total of 255 different networks based on poly(trimethylene carbonate) (PTMC)-, poly(d,l-lactide) (PDLLA)-, poly(ε-caprolactone) (PCL)- and poly(ethylene glycol) (PEG) macromers were synthesized simultaneously and screened for their ability to allow the adhesion of human mesenchymal stem cells (hMSCs) in a high throughput-like manner. Of these networks, several hydrogels could be identified that were able to take up large amounts of water while at the same time allowed the adhesion of cells. By synthesizing these hydrogel networks anew and analyzing the cell adhesion and proliferation behavior of human mesenchymal stem cells to these synthetic hydrogels in more detail, it was confirmed that mixed-macromer hydrogel networks prepared from equal amounts of PTMC-dMA 4k, PDLLA-dMA 4k, PCL-dMA 4k, PEG-dMA 4k, and PEG-dMA 10k and hydrogel networks prepared from PTMC-dMA 4k, PDLLA 4k, PEG-dMA 4k, PTMC-dMA 10k and PEG-dMA 10k were highly hydrophilic (water uptake was respectively 181 ± 2 and 197 ± 18 wt % water) and allowed very good cell adhesion and proliferation. Furthermore, these networks were extremely resilient in the hydrated state, with tearing energies of respectively 0.64 ± 0.34 and 0.27 ± 0.04 kJ/m(2). This is much higher than other synthetic hydrogels described in literature and close to articular cartilage (1 kJ/m(2)).
合成水凝胶的主要缺点是其机械性能较差,以及促进细胞附着和增殖的能力有限。通过在溶液中以组合方式对二甲基丙烯酸酯官能化低聚物(大分子单体)混合物进行光交联,制备出了具有高吸水性以及显著促进细胞黏附与增殖能力的合成水凝胶。同时合成了总共255种基于聚碳酸三亚甲酯(PTMC)、聚(d,l-丙交酯)(PDLLA)、聚己内酯(PCL)和聚乙二醇(PEG)大分子单体的不同网络,并以类似高通量的方式筛选它们支持人间充质干细胞(hMSCs)黏附的能力。在这些网络中,可以鉴定出几种能够吸收大量水分同时又能支持细胞黏附的水凝胶。通过重新合成这些水凝胶网络,并更详细地分析人间充质干细胞对这些合成水凝胶的细胞黏附与增殖行为,证实了由等量的PTMC-dMA 4k、PDLLA-dMA 4k、PCL-dMA 4k、PEG-dMA 4k和PEG-dMA 10k制备的混合大分子单体水凝胶网络以及由PTMC-dMA 4k、PDLLA 4k、PEG-dMA 4k、PTMC-dMA 10k和PEG-dMA 10k制备的水凝胶网络具有高度亲水性(吸水率分别为181±2和197±18 wt%水),并能实现非常良好的细胞黏附与增殖。此外,这些网络在水合状态下具有极高的弹性,撕裂能分别为0.64±0.34和0.27±0.04 kJ/m²。这比文献中描述的其他合成水凝胶高得多,且接近关节软骨(1 kJ/m²)。