Platelets: the first cellular responders in the foreign body response to blood-contacting biomaterials.

Implanting biomaterials gives rise to the foreign body response (FBR), a complex cascade consisting of blood-material interactions, provisional matrix formation, inflammation, wound healing, and remodeling. While tissue engineering seeks to harness this host response to transform implanted materials into living tissue, the FBR can drive various complications that undermine construct function and longevity with significant clinical impact for patients. The past several decades yielded important insights regarding protein adsorption dynamics and the subsequent cellular responders that exert significant influence over the inflammatory and healing processes governing the FBR. However, the contributions of platelets have often been overlooked and continue to remain underappreciated, especially compared to other major players like macrophages and fibroblasts. Beyond their classical role in hemostasis, platelet-derived products have long been explored for regenerative applications, and platelets are now recognized as immunomodulators. In this review, we highlight platelets as the first cellular responders to biomaterial implantation, emphasizing their active and multifaceted roles in the FBR. We further propose platelet modulation as a strategy to optimize host-material interactions and improve patient outcomes. A complete understanding of the FBR for blood-contacting biomaterials must begin with the arrival of the platelet.