Foreign body reaction is triggered in vivo by cellular mechanosensing of implants stiffer than host tissue

Medical implants offer a unique and powerful therapeutic approach in many areas of medicine. However, their lifetime is often limited as they may cause a foreign body reaction (FBR) leading to their encapsulation by scar tissue1–4. Despite the importance of this process, how cells recognise implanted materials is still poorly understood5, 6. Here, we show how the mechanical mismatch between implants and host tissue leads to FBR. Fibroblasts and macrophages, which are both crucially involved in mediating FBR, became activated when cultured on materials just above the stiffness of healthy tissue. Coating stiff implants with a thin layer of hydrogel or silicone with a tissue-like elastic modulus (∼20 kPa in subcutaneous and ∼2 kPa in peripheral nerve implants) or softer significantly reduced inflammation and fibrosis three months after implantation. Materials stiffer than the host tissue led to nuclear localisation of the mechanosensitive transcriptional regulator YAP in neighbouring cells in vivo, confirming mechanotransduction. The alleviation of FBR by soft coatings not exceeding the stiffness of the host tissue provides a strategy to achieve long-term implant stability without extensive modification of current implant manufacturing techniques, facilitating clinical translation.