Exploring the Overlooked Roles and Mechanisms of Fibroblasts in the Foreign Body Response.

Significance: Foreign body response (FBR), wherein a fibrotic capsule forms around an implanted structure, is a common surgical complication that often leads to pain, discomfort, and eventual revision surgeries. Although believed to have some mechanistic overlap with normal wound healing, much remains to be discovered about the specific mechanism by which this occurs. Recent Advances: Current understanding of FBR has focused on the roles of the immune system and the biomaterial, both major contributors to FBR. However, another key player, the fibroblast, is often overlooked. This review summarizes key contributors of FBR, focusing on the roles of fibroblasts. As much remains to be discovered about fibroblasts' specific roles in FBR, we draw on current knowledge of fibroblast subpopulations and functions during wound healing. We also provide an overview on candidate biomaterials and signaling pathways involved in FBR. Critical Issues and Future Directions: While the global implantable medical devices market is considerable and continues to appreciate in value, FBR remains one of the most common surgical implant complications. In parallel with the continued development of candidate biomaterials, further exploration of potential fibroblast subpopulations at a transcriptional level would provide key insights into further understanding the underlying mechanisms by which fibrous encapsulation occurs, and unveil novel directions for antifibrotic and regenerative therapies in the future.