Shuo Chen, Xinlin Liu, Huitao Qi, Dan Wang, Qian Kong, Zhijuan Ai, Shuya Liang, Zhongmin Geng
A revolutionary development in biomaterial science, intracellular gelation technology allows for the in situ creation of three-dimensional polymer networks inside the cytoplasm to create an "artificial cytoskeleton". The cellular physicochemical microenvironment can be precisely manipulated using this method. In contrast to traditional biomaterials that function externally, intracellular gelation uses an "inside-out" approach to directly alter cellular states. The design principles, biological effects, and biomedical applications of mechanism-responsive hydrogel materials are highlighted in this review, which methodically summarizes recent advancements in the field worldwide. Even with all of its transformative capabilities, the area still encounters many limitations, such as safety concerns regarding the use of artificial cytoskeletons in the long run, poor efficacy of gelation heterogeneously in the single cell, and the absence of any in vivo targeted technique. This review provides a comprehensive overview of intracellular gelation technology, covering triggering mechanisms, material systems, biological effects, biomedical applications, and future perspectives.