Near‐Infrared Light‐Sensitive Polyvinyl Alcohol Hydrogel Photoresist for Spatiotemporal Control of Cell‐Instructive 3D Microenvironments,Advanced Materials

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Near‐Infrared Light‐Sensitive Polyvinyl Alcohol Hydrogel Photoresist for Spatiotemporal Control of Cell‐Instructive 3D Microenvironments
Advanced Materials ( IF 27.4 ) Pub Date : 2018-01-15 , DOI: 10.1002/adma.201705564
Xiao-Hua Qin ₁ , Xiaopu Wang ₂ , Markus Rottmar ₁ , Bradley J. Nelson ₂ , Katharina Maniura-Weber ₁

Affiliation

Advanced hydrogel systems that allow precise control of cells and their 3D microenvironments are needed in tissue engineering, disease modeling, and drug screening. Multiphoton lithography (MPL) allows true 3D microfabrication of complex objects, but its biological application requires a cell‐compatible hydrogel resist that is sufficiently photosensitive, cell‐degradable, and permissive to support 3D cell growth. Here, an extremely photosensitive cell‐responsive hydrogel composed of peptide‐crosslinked polyvinyl alcohol (PVA) is designed to expand the biological applications of MPL. PVA hydrogels are formed rapidly by ultraviolet light within 1 min in the presence of cells, providing fully synthetic matrices that are instructive for cell‐matrix remodeling, multicellular morphogenesis, and protease‐mediated cell invasion. By focusing a multiphoton laser into a cell‐laden PVA hydrogel, cell‐instructive extracellular cues are site‐specifically attached to the PVA matrix. Cell invasion is thus precisely guided in 3D with micrometer‐scale spatial resolution. This robust hydrogel enables, for the first time, ultrafast MPL of cell‐responsive synthetic matrices at writing speeds up to 50 mm s⁻¹. This approach should enable facile photochemical construction and manipulation of 3D cellular microenvironments with unprecedented flexibility and precision.

中文翻译：

近红外光敏聚乙烯醇水凝胶光致抗蚀剂，用于时空控制细胞指导性3D微环境。

在组织工程，疾病建模和药物筛选中，需要能够精确控制细胞及其3D微环境的高级水凝胶系统。多光子光刻（MPL）可以对复杂的物体进行真正的3D微加工，但其生物学应用需要具有细胞相容性的水凝胶抗蚀剂，该抗蚀剂必须具有足够的感光性，细胞可降解性并允许3D细胞生长。在这里，由肽交联的聚乙烯醇（PVA）组成的极易感光的细胞反应性水凝胶旨在扩展MPL的生物学应用。在存在细胞的情况下，紫外线在1分钟内迅速形成PVA水凝胶，提供了完全合成的基质，对细胞基质重构，多细胞形态发生和蛋白酶介导的细胞入侵具有指导意义。通过将多光子激光聚焦到载有细胞的PVA水凝胶中，可将指示细胞的细胞外提示位点特异性地附着到PVA基质上。因此，可以在微米级的空间分辨率下以3D精确地引导细胞入侵。这种坚固的水凝胶首次实现了细胞响应性合成基质的超快MPL，写入速度高达50 mm s^-1。这种方法应该能够以前所未有的灵活性和精度实现简便的光化学构建和3D细胞微环境的操纵。

更新日期：2018-01-15

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