Inflammatory environment-adaptive patterned surface for spatiotemporal immunomodulation of macrophages
Inflammatory environment-adaptive patterned surface for spatiotemporal immunomodulation of macrophages
复制标题
用于巨噬细胞时空免疫调节的炎症环境适应性图案化表面
DOI：
10.1016/j.actbio.2022.09.055
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发表时间：
2022
影响因子：
9.7
通讯作者：
Lie Ma
中科院分区：
文献类型：
--
作者：
Yilun Luo;Peiqi Yuan;Sentao Hu;Hanwen Wang;Haiqi Zhang;Lie Ma
设计具有精确免疫调节的生物材料可以帮助破译巨噬细胞和生物材料之间的动态相互作用，以匹配组织愈合过程。虽然已有一些先进的刺激响应性免疫调节生物材料被报道用于细胞动力学调节，但大多数触发器需要人工干预的外部刺激，存在不可避免的误差和不确定性。因此，开发具有自适应能力的免疫调节生物材料，可以识别炎症信号，在微环境触发下时空改变其性质，并提供反馈以实现不同愈合阶段的巨噬细胞调节，已成为一种有前途的策略。在这项工作中，我们开发了一种炎症适应性Arg-Gly-Asp（RGD）图案化的表面，用于巨噬细胞的时空免疫调节。我们采用光刻技术制备了具有巯基官能化的RGD图案表面的甲基丙烯酸酯化透明质酸（MA-HA）水凝胶。然后，硫醇官能化的含有ROS可切割接头的RGD填充剩余位点，从而获得具有暂时均匀的RGD的动态表面。在炎症激活的巨噬细胞过度产生ROS的情况下，连接体被切割，均质的RGD表面转化为RGD图案化的表面，从而引发巨噬细胞的伸长，并因此上调了TNF-β 1、IL-10和TNF-β1的表达，表明向抗炎表型的极化。开发用于时空调节巨噬细胞极化的炎症环境适应性表面为愈合匹配的免疫调节提供了精确和智能的策略，以促进愈合结果。重要性声明：设计具有精确免疫调节的生物材料可以帮助破译巨噬细胞与生物材料之间的动态相互作用，以匹配组织修复过程。一些免疫调节生物材料被报道用于细胞动态调节，而大多数触发物需要外部手动干预。因此，我们开发了一种具有炎症适应性图案化表面的免疫调节生物材料，其可以识别异常信号并在微环境触发下时空地改变其性质，并提供反馈以实现不同阶段的巨噬细胞调节。动态表面可以适应微环境的变化，动态地按需匹配细胞行为和组织愈合过程，而无需外部人工干预。此外，该表面在组织修复过程中实现了巨噬细胞与促炎和抗炎表型的平衡。
Designing biomaterials with precise immunomodulation can help to decipher the dynamic interactions between macrophages and biomaterials to match the tissue healing process. Although some advanced stimuli-responsive immunomodulatory biomaterials were reported for cell dynamic modulation, while most triggers need external stimuli by manual intervention, there would be the inevitable errors and uncertainties. Thus, developing immunomodulatory biomaterials with adaptive abilities, which can recognize the inflammation signals, change their properties spatiotemporally under the microenvironment triggers, and provide feedback to realize macrophages modulation in different healing stages, has become a promising strategy. In this work, we developed an inflammation-adaptive Arg-Gly-Asp (RGD) -patterned surface for spatiotemporal immunomodulation of macrophage. We fabricated a methacrylated hyaluronic acid (MA-HA) hydrogel with thiol-functionalized RGD-patterned surface by employing photolithography technology. Then, thiol-functionalized RGD contained ROS-cleavable linker was filled the remaining sites and consequently, a dynamic surface with temporary homogeneous RGD was obtained. Under the overproduction of ROS by the inflammation-activated macrophages, the linker was cleaved, and the homogeneous RGD surface was transformed to the RGD patterned surface, which triggered elongation of macrophages and consequently the upregulated expressions of arginase-1, IL-10 and TNF-β1, indicating the polarization toward to anti-inflammatory phenotype. Developing inflammatory environment-adaptive surface for spatiotemporal modulation of macrophages polarization provides a precise and smart strategy for the healing-matched immunomodulation to facilitate healing outcomes. STATEMENT OF SIGNIFICANCE: Designing biomaterials with precise immunomodulation can help to decipher the dynamic interactions between macrophages and biomaterials to match tissue repair process. Some immunomodulatory biomaterials were reported for cell dynamic modulation, while most triggers need external manual intervention. Thus, we developed an immunomodulatory biomaterial with inflammation-adaptive patterned surface, which can recognize abnormal signals and change its properties spatiotemporally under the microenvironment triggers, and provide feedback to realize macrophages modulation in different stages. The dynamic surface can adapt to the changes of microenvironment and dynamically to match the cell behavior and tissue healing process on demand without external manual intervention. Additionally, the surface achieves the balance of macrophages with pro- and anti-inflammatory phenotypes in the tissue repair process.