Abstract / Summary
Abstract Laminin (LN), a major component of the extracellular matrix (ECM), modulates tissue morphogenesis and is known to act as a reservoir for growth factors (GFs). Here we show, for the first time, that laminins and fibronectin also bind interleukins (ILs), through sites and binding behaviours distinct from those governing GF binding and independent of heparin. This finding extends the reservoir function of the ECM beyond growth factor biology and opens a matrix-biology perspective on immune regulation. We further show that LN111 potentiates IL-10 signalling during M2c macrophage polarization via crosstalk with the integrin α6 (ITGA6) axis. As a translational application, a PEG-maleimide (PEG-MAL) hydrogel functionalized with LN111 for IL-10 delivery significantly improves wound healing in a murine model of type 2 diabetes. During this work, we found that IL-binding sites sterically interfere with commercial antibodies. To address this, we developed a high-throughput approach that replaces immunolabelling with chemical labelling and combines AI-assisted docking with wet-lab validation to screen binding sites within large ECM proteins.