In the biological microenvironment, cells are surrounded by an extracellular matrix (ECM), with which they dynamically interact during various biological processes. Specifically, the physical and chemical properties of the ECM work cooperatively to influence the behavior and fate of cells directly and indirectly, which invokes various physiological responses in the body. Hence, efficient strategies to modulate cellular responses for a specific purpose have become important for various scientific fields such as biology, pharmacy, and medicine. Among many approaches, the utilization of biomaterials has been studied the most because they can be meticulously engineered to mimic cellular modulatory behavior. For such careful engineering, studies on physical modulation (e.g., ECM topography, stiffness, and wettability) and chemical manipulation (e.g., composition and soluble and surface biosignals) have been actively conducted. At present, the scope of research is being shifted from static (considering only the initial environment and the effects of each element) to biomimetic dynamic (including the concepts of time and gradient) modulation in both physical and chemical manipulations. This review provides an overall perspective on how the static and dynamic biomaterials are actively engineered to modulate targeted cellular responses while highlighting the importance and advance from static modulation to biomimetic dynamic modulation for biomedical applications.

In article number 2004300, Young Keun Kim, Heemin Kang, and co‐workers report a magnetic nano‐barcoding system that enables unique tunability of ligand frequency and nano‐sequences to effectively regulate stem cell adhesion with no systemic toxicity in vivo. Low‐frequency and terminally sequenced nano‐ligands facilitate focal adhesion, mechanotransduction, and differentiation of stem cells.

In the native extracellular matrix, collagen fibrils regulate stem cell fate and tissue regeneration by modulating the number of serial kinks via intramolecular kinking and unkinking, which affects integrin ligation. However, biomimetic materials composed solely of multi‐kink‐bearing molecules for dynamic regulation of ligand exposure remain limited. In this study, we designed materials composed solely of liganded multiple kink‐bearing molecules with a tunable number of kink points (mono‐kink, tri‐kink, and penta‐kink molecules), including flexible linkers and densely packed via intermolecular interactions, are designed. Near‐infrared‐upconverted ultraviolet light and visible light induce multiple kinking and unkinking of liganded multiple kink‐bearing molecules conjugated to upconversion nanoparticle‐coated materials, inducing kinked and unkinked states, respectively. Tri‐kinking and unkinking mediate the effective regulation of ligand masking and exposure, respectively, by modulating intermolecular interactions, while mono‐kink and penta‐kink molecules continuously expose the ligands regardless of their kinking/unkinking state. Tri‐unkinking cyclically stimulates integrin ligation and focal adhesion‐mediated stem cell mechanotransduction and differentiation in vivo, which are inhibited by tri‐kinking. This study presents a newly developed reversibly switchable multi‐kink molecule‐conjugated surface for dynamic regulation of ligand exposure and stem cell responses, providing a useful modality for regulating cell–material interactions and stem cell fate in vivo.