Lymphocytes and their Involvement in the Foreign Body Response to Biomaterials and Tissue Repair

Lymphocytes, long regarded as central actors of adaptive immunity, are increasingly recognized as key regulators of the foreign body response (FBR) to biomaterials. Their presence shapes the chronic phases of inflammation, fibrosis, angiogenesis, and regenerative outcomes after implantation. This review summarizes the roles of T cells, B cells, and natural killer (NK) cells in biomaterial-associated immune responses, with a particular focus on protein adsorption, antigen recognition, cytokine secretion, and downstream interactions with macrophages, fibroblasts, and endothelial cells. Evidence indicates that T-cell polarization into Th1/Th17 subsets promotes pro-inflammatory reactions, while Th2 and regulatory T cells (Tregs) support constructive remodeling and resolution. B cells contribute through antibody production and cytokine release, which may foster fibrosis or support debris clearance. NK cells serve as early stress sensors, releasing cytotoxic mediators and pro-angiogenic factors that influence vascularization and tissue repair. Collectively, lymphocytes are pivotal but underexplored players in biomaterial integration. Incorporating lymphocyte biology into material design and surface modification strategies offers promising avenues to guide immune cascades toward predictable and regenerative outcomes.