Tuning liganded nanocrack geometry for dynamic regulation of host macrophages

Abstract

Topographical cracks in native tissues such as brain, skin, and bone dynamically remodel across geometries to maintain tissue homeostasis. Disruptions in interactions between crack features (e.g., width and depth) and cells can impair immune responses, leading to disorder development, such as eczema, psoriasis, and angiogenesis defects. While topographical crack geometries across various scales regulate immune cell responses, precise and dynamic tuning of nanocrack geometries at tens-of-nanometers scale, critical for understanding molecular interactions between cells and extracellular matrix that dictate integrin responses, remains elusive. Herein, nanocracked materials exhibiting topographical cracks with widths tuned at integrin-presenting filopodia scale are developed by modifying hydrophobic properties of bicontinuous microemulsions, featuring magnetically responsive liganded crack-modulatable particles (CMPs) via elastic polymer linkers. CMPs can be dynamically modulated by magnetic field application, enabling transitions between deep and shallow crack states to regulate macrophage integrin recruitment, adhesion, and polarization. Narrow cracks (50 nm), smaller than filopodia, restrict infiltration and limit integrin engagement, whereas Wide cracks (110 nm) promote strong adhesion. Moderate cracks (80 nm) allow minimal adhesion in deep crack state but significantly enhance integrin recruitment upon magnetic activation to shallow crack state, facilitating macrophage polarization toward an anti-inflammatory phenotype. This is the first demonstration of dynamic nanocrack system for host cell regulation. This breakthrough offers new insights into the role of hierarchical crack architectures in regulating immunomodulation, regenerative medicine, and wound healing.