biostudies-literatureMei Fthe Key Project of Hubei ProvinceNational Natural Science Foundation of ChinaChina Postdoctoral Science Foundationthe China Postdoctoral Science Foundationthe National Key R&D Program of ChinaNational Key Research and Development Program of Chinathe National Natural Science Foundation of Chinae13640https://www.ebi.ac.uk/biostudies/studies/S-EPMC11294424biostudies-literatureUnknown57(8)Macrophages play a pivotal role in the immunological cascade activated in response to biomedical implants, which predetermine acceptance or rejection of implants by the host via pro- and anti-inflammatory polarisation states. The role of chemical signals in macrophage polarisation is well-established, but how physical cues regulate macrophage function that may play a fundamental role in implant-bone interface, remains poorly understood. Here we find that bone marrow-derived macrophages (BMDM) cultured on polyacrylamide gels of varying stiffness exhibit different polarisation states. BMDM are 'primed' to a pro-inflammatory M1 phenotype on stiff substrates, while to an anti-inflammatory M2 phenotype on soft and medium stiffness substrates. It is further observed that matrix stiffening increaCell proliferationMatrix stiffness regulates macrophage polarisation via the Piezo1-YAP signalling axis.PMC112944242021M7002792023T1600292021YFC2400400/042020BCA0728220112382221003Guo YChen LXie MZhou YZhang SYang CDing SHuang XMei FWang YHeng BCLiu FDeng XfalseMatrix stiffness regulates macrophage polarisation via the Piezo1-YAP signalling axis.Macrophages play a pivotal role in the immunological cascade activated in response to biomedical implants, which predetermine acceptance or rejection of implants by the host via pro- and anti-inflammatory polarisation states. The role of chemical signals in macrophage polarisation is well-established, but how physical cues regulate macrophage function that may play a fundamental role in implant-bone interface, remains poorly understood. Here we find that bone marrow-derived macrophages (BMDM) cultured on polyacrylamide gels of varying stiffness exhibit different polarisation states. BMDM are 'primed' to a pro-inflammatory M1 phenotype on stiff substrates, while to an anti-inflammatory M2 phenotype on soft and medium stiffness substrates. It is further observed that matrix stiffening increa2024-01-01T00:00:00Z2024 Aug2026-06-03T00:37:57.372Z2025-02-19T02:27:29.908ZS-EPMC112944243855684010.1111/cpr.13640