Dadoo Nayereh, Gramlich William M
Department of Chemistry, 5706 Aubert Hall, Room 154, University of Maine, Orono, Maine 04469-5706, United States.
ACS Biomater Sci Eng. 2016 Aug 8;2(8):1341-1350. doi: 10.1021/acsbiomaterials.6b00259. Epub 2016 Jul 6.
Current methods to spatiotemporally modify stimuli response in hydrogels are typically subtractive and lead to a decrease in response. To increase the breadth of hydrogel applications and biomedical systems, new formulations are needed that can introduce and increase stimuli response spatiotemporally in hydrogels. In this work, the light-induced thiol-norbornene click chemistry reaction was used to modify the stimuli response of robust hyaluronic acid hydrogels through an additive process in spatiotemporal fashion, overcoming this limitation. These stimuli-responsive hydrogels were made from norbornene-functionalized hyaluronic acid (NorHA) cross-linked with thermoresponsive dithiol-terminated poly(-isopropylacrylamide) (DTPN). Variation of the cross-linker molecular weight and gelation conditions led to a range of compression modulus (5 to 54 kPa) and mass loss (9 to 33%) upon heating to 37 °C while retaining a majority of NorHA in the hydrogel. The thermoresponse of these hydrogels could be controlled not only by the cross-link density but also by heating to 55 °C to increase the dewatering of the hydrogels. The stimuli response of the hydrogels was temporally increased by introducing additional DTPN and UV initiator to an original hydrogel with subsequent irradiation. This modification was extended to spatiotemporally changing the stimuli response by photopatterning DTPN into a NorHA hydrogel, yielding a hydrogel that changed shape and topology through heating. Furthermore, human mesenchymal stem cells could adhere and proliferate on the DTPN-patterned surface, demonstrating that the materials could be used for studies where cells are present.
当前在水凝胶中对刺激响应进行时空修饰的方法通常是减法式的，会导致响应降低。为了扩大水凝胶应用和生物医学系统的范围，需要新的配方，能够在水凝胶中时空引入并增强刺激响应。在这项工作中，利用光诱导的硫醇-降冰片烯点击化学反应，通过一种时空加法过程来修饰坚固的透明质酸水凝胶的刺激响应，克服了这一限制。这些刺激响应性水凝胶由降冰片烯功能化的透明质酸（NorHA）与热响应性二硫醇封端的聚（N-异丙基丙烯酰胺）（DTPN）交联而成。交联剂分子量和凝胶化条件的变化导致加热至37°C时压缩模量范围为5至54 kPa，质量损失为9至33%，同时水凝胶中保留了大部分NorHA。这些水凝胶的热响应不仅可以通过交联密度来控制，还可以通过加热至55°C来增加水凝胶的脱水程度来控制。通过向原始水凝胶中引入额外的DTPN和紫外线引发剂并随后进行照射，水凝胶的刺激响应在时间上得到增强。这种修饰扩展到通过将DTPN光图案化到NorHA水凝胶中来时空改变刺激响应，产生一种通过加热改变形状和拓扑结构的水凝胶。此外，人间充质干细胞可以在DTPN图案化的表面上粘附和增殖，表明这些材料可用于有细胞存在的研究。
