Phosphatidylserine-functional polydimethylsiloxane substrates regulate macrophage M2 polarization via...

Area of Science:

• Biomaterials Science
• Immunology
• Cell Biology

Background:

• Macrophages are crucial for implant success, but their polarization (M1/M2) on implant surfaces is complex.
• Understanding how physical and biochemical cues regulate macrophage behavior is key for advanced biomaterials.

Purpose of the Study:

• To investigate the combined effects of substrate modulus and phosphatidylserine (PS) modification on macrophage polarization.
• To elucidate the underlying mechanisms of PS-mediated immunomodulation on polydimethylsiloxane (PDMS) substrates.

Main Methods:

• Fabrication of PDMS substrates with varying moduli (1-100 kPa) and PS modification.
• Assessment of macrophage polarization (M1/M2) in vitro and in vivo.
• Analysis of cellular signaling pathways including integrin clustering, cytoskeletal dynamics, YAP, Piezo1, and inflammatory markers.

Main Results:

• PS modification enhanced M2 polarization and suppressed M1 activation, an effect amplified by lower substrate modulus.
• In vivo studies confirmed reduced M1 activation and increased M2 polarization with low-modulus PS-PDMS.
• Lower modulus reduced integrin clustering, YAP activation, and inflammation via the Piezo1 pathway, while promoting M2 markers.

Conclusions:

• Substrate modulus synergistically enhances PS-mediated M2 macrophage polarization.
• Low-modulus, PS-functionalized biomaterials can effectively modulate macrophage responses for improved implant performance.
• This study provides a foundation for designing next-generation immunomodulatory biomaterials.