Mechanosensing by TRPV4 mediates stiffness-induced foreign body response and giant cell formation.

ABSTRACT: Implantation of biomaterials or devices into soft tissue often leads to the development of the foreign body response (FBR), an inflammatory condition that can cause implant failure, tissue injury, and death of the patient. Macrophages accumulate and fuse to generate destructive foreign body giant cells (FBGCs) at the tissue-implant interface, leading to the development of fibrous scar tissue around the implant that is generated by myofibroblasts. We previously showed that the FBR in vivo and FBGC formation in vitro require transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel. Here, we report that TRPV4 was required specifically for the FBR induced by implant stiffness independently of biochemical cues and for intracellular stiffening that promotes FBGC formation

SUBMITTER: Goswami R 

PROVIDER: S-EPMC9976933 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature