Synthesis and orthogonal photopatterning of hyaluronic acid hydrogels with thiol-norbornene chemistry.
Synthesis and orthogonal photopatterning of hyaluronic acid hydrogels with thiol-norbornene chemistry.
复制标题
DOI：
10.1016/j.biomaterials.2013.08.089
复制
发表时间：
2013-12
期刊：
影响因子：
14
通讯作者：
Burdick, Jason A.
中科院分区：
文献类型：
--
作者：
Gramlich, William M.;Kim, Iris L.;Burdick, Jason A.
水凝胶内化学和机械信号的模式化使其在生物医学应用中作为细胞微环境使用时具有更高的复杂性。具体而言，光图案化技术正在兴起，用于引入水凝胶性质的异质性；然而，目前所采用的系统在可获得的性质范围以及将机械性质与化学信号变化解耦方面存在局限性。在此，我们提出一种正交光图案化系统，该系统利用硫醇 - 降冰片烯化学，由于可用于二次反应的活性位点数量多，允许对水凝胶进行广泛的修饰，包括引入多种信号。透明质酸用降冰片烯基团（NorHA）进行功能化，并与二硫醇反应生成具有广泛机械性能的无毒水凝胶。例如，对于改性程度为20%的4 wt% NorHA，只需改变交联剂的用量，就可获得从约1 kPa到约70 kPa的水凝胶力学性能。通过限制初始交联程度，合成了带有剩余悬垂降冰片烯基团的NorHA凝胶，这些基团在光和引发剂存在的情况下可与含硫醇的分子发生反应，包括具有空间控制。与二硫醇交联剂的二次反应改变了机械性能，而与单硫醇肽的反应对凝胶弹性模量没有影响。这种正交化学依次用于将多种肽图案化到单个水凝胶中，证明了该系统在形成复杂水凝胶方面的稳健性。
The patterning of chemical and mechanical signals within hydrogels permits added complexity towards their use as cell microenvironments for biomedical applications. Specifically, photopatterning is emerging to introduce heterogeneity in hydrogel properties; however, currently employed systems are limited in the range of properties that can be obtained, as well as in decoupling mechanical properties from changes in chemical signals. Here, we present an orthogonal photopatterning system that utilizes thiol-norbornene chemistry and permits extensive hydrogel modification, including with multiple signals, due to the number of reactive handles accessible for secondary reaction. Hyaluronic acid was functionalized with norbornene groups (NorHA) and reacted with di-thiols to create non-toxic hydrogels with a wide range of mechanical properties. For example, for 4 wt% NorHA at 20% modification, hydrogel mechanics from ~1 kPa up to ~70 kPa could be obtained by simply changing the amount of crosslinker. By limiting the initial extent of crosslinking, NorHA gels were synthesized with remaining pendent norbornene groups that could be reacted with thiol containing molecules in the presence of light and an initiator, including with spatial control. Secondary reactions with a di-thiol crosslinker changed mechanical properties, whereas reaction with mono-thiol peptides had no influence on the gel elastic modulus. This orthogonal chemistry was used sequentially to pattern multiple peptides into a single hydrogel, demonstrating the robustness of this system for the formation of complex hydrogels.
登录
查看更多内容
影响因子：
41.2
作者：
Khetan S;Guvendiren M;Legant WR;Cohen DM;Chen CS;Burdick JA
通讯作者：
Burdick JA
影响因子：
14
作者：
Lee, Soo-Hong;Moon, James J.;West, Jennifer L.
通讯作者：
West, Jennifer L.
影响因子：
9.7
作者：
Gould, Sarah T.;Darling, Nicole J.;Anseth, Kristi S.
通讯作者：
Anseth, Kristi S.
影响因子：
29.4
作者：
Fairbanks, Benjamin D;Schwartz, Michael P;Halevi, Alexandra E;Nuttelman, Charles R;Bowman, Christopher N;Anseth, Kristi S
通讯作者：
Anseth, Kristi S
影响因子：
16.6
作者：
Guvendiren, Murat;Burdick, Jason A.
通讯作者：
Burdick, Jason A.