Gel's Molecular Weight Steers Immune Cells Toward Healing Mode
Researchers demonstrated that thicker hyaluronic acid in lab-grown gels pushes immune cells to adopt anti-inflammatory behavior—a finding that could accelerate development of regenerative medicine implants and immunotherapy devices. The discovery, made in realistic 3D tissue models rather than flat petri dishes, suggests material engineers can now design scaffolds that actively reprogram immune responses.
Originaltitel: Molecular Weight-Driven Tunable Hyaluronic Acid–Based Hydrogels Modulate Immune Polarization in Three-Dimensional Microenvironments
Macrophages exhibit phenotypic plasticity that is strongly influenced by their surrounding microenvironment, including extracellular matrix (ECM) components. Hyaluronic acid (HA), a major glycosaminoglycan in ECM, has immunomodulatory effects that are highly dependent on its molecular weight (MW). However, most previous studies have been limited to two-dimensional (2D) culture systems, which were unable to accurately replicate the in vivo environment. In this study, we utilized a three-dimensional (3D) culture system based on HA-based hydrogels to better understand the MW-dependent immunomodulatory effects of HA on macrophages under more physiologically relevant conditions. Three different MWs of HA were chemically modified and cross-linked with PEG-SH4 to form hydrogels with distinct biophysical properties. Immortalized macrophages were encapsulated within these hydrogels and assessed for the expression of both pro-inflammatory and anti-inflammatory markers. Notably, hydrogels with high-MW HA significantly upregulated the expression of anti-inflammatory markers, indicating that the immunomodulatory effects of HA in 3D culture are affected by its biophysical characteristics. Our findings demonstrate the potential of HA-based hydrogels as customizable ECM-mimetic scaffolds for modulating immune responses in regenerative medicine applications.