Molecular signaling in biomaterial-induced foreign body response: current perspectives

The foreign body response (FBR) is an inevitable host response to implanted materials, initiated by tissue injury and marked by a cascade of inflammatory and fibrotic processes. Following implantation, local tissue damage triggers acute inflammation, characterized by immune cell recruitment and activation. Over time, this response advances to a chronic fibrotic phase marked by dense extracellular matrix deposition and fibrous capsule formation, which can encapsulate and, in some cases, functionally isolate the implant. Both the early inflammatory and late fibrotic stages of FBR can severely impair the performance and longevity of implants. FBR is governed by a dynamic and multifaceted network of molecular signaling pathways, cellular mechanosensing mechanisms, and intercellular communication. Despite its clinical significance, the molecular underpinnings of FBR remain incompletely defined. A deeper molecular understanding is critical for the rational design of next-generation biomaterials that mitigate adverse host responses and improve biocompatibility. In this review, we provide the first comprehensive overview of the current knowledge of the molecular events driving FBR, with the goal of informing strategies for therapeutic modulation and biomaterial innovation.