Viscoelastic hydrogel primed CAR-macrophage for pulmonary fibrosis treatment

Journal article

CAR-macrophage (CAR-M) therapy holds promise for the treatment of tumor and fibrotic diseases, yet genetic engineering remains the main efficacy-enhancing approach. Here we develop a non-genetic strategy using viscoelastic hydrogel to mechanically prime CAR-Ms. CAR-Ms exhibit potent phagocytosis of activated fibroblasts and collagen-degradation capacity, and hydrogel priming further enhances their cytotoxicity. Mechanistically, viscoelastic hydrogel priming reduces CAR-M membrane tension, which triggers membrane CAR to disassemble from clusters into dispersed monomers and dimers, leading to enhanced downstream signaling. In pulmonary fibrosis models, hydrogel-primed CAR-Ms demonstrate superior therapeutic outcomes, showing fibrosis reduction and microenvironment improvement. This study highlights CAR-M therapy's potential for pulmonary fibrosis treatment and offers a distinct approach to improve CAR-M efficacy by physical stimuli.

Authors: Zhang, Y; Liu, Z; Kong, W; Ao, Y; Zhang, R

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Communications
• Volume: 17
• Issue: 1
• Pages: 1663-1663
• Publication date: 2026-02-13
• DOI: 10.1038/s41467-025-68033-4
• EISSN: 2041-1723
• ISSN: 2041-1723
• Language: English
• Keywords: Phagocytosis; Viscoelasticity; Pulmonary fibrosis; Self-healing hydrogels; Fibrosis; Idiopathic pulmonary fibrosis; Priming (agriculture)