Fibrinogen and Fibrin as Growth Factor Regulators: Pathological Implications, and Translational Opportunities

Fibrinogen and fibrin are multifunctional plasma proteins that play central roles in hemostasis, tissue repair, and extracellular matrix organization. Their complex molecular architecture enables specific interactions with key growth factors, including fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), and others, promoting growth factor localization, protection from proteolysis, and enhanced signaling. These interactions regulate essential biological processes such as angiogenesis, cell proliferation, and wound healing. Dysregulation of fibrinogen-fibrin contributes to pathological conditions, including thrombosis, chronic inflammation, cancer progression, neurological complications, and impaired tissue regeneration. Recent advances in fibrin-based biomaterials leverage these molecular interactions for controlled therapeutic delivery and regenerative medicine applications. Emerging recombinant fibrinogen technologies and precision biomaterial engineering further expand the translational potential of targeting fibrinogen-fibrin growth factor interactions to improve clinical outcomes. This review offers an integrated overview of fibrinogen and fibrin biology, detailing their molecular interactions with growth factors, their pathological implications, clinical significance, and future research directions, emphasizing the translational potential of leveraging these interactions to advance human health.