Kenzi-Alayna Campbell, Sanjay P Tirupattur, Gia Katwa, Laxmansa C Katwa
Collagen is the most abundant protein in the human body and a vital component of the extracellular matrix (ECM), where it maintains structural architecture, strength, and mechanical stability throughout the body. Collagen undergoes continuous turnover and remodeling mediated by matrix metalloproteinases (MMPs) and other proteases to generate collagen peptide fragments (CPFs). CPFs were long considered inert byproducts of collagen turnover but are now recognized to have two overlapping roles: as circulating and urinary biomarkers of ECM remodeling, and as beneficial or adverse bioactive matrikines that directly regulate inflammation, angiogenesis, fibrosis, immune responses, and tissue remodeling. This review focuses on current evidence regarding the biological activities of various CPFs across cardiovascular, cancer, and pulmonary systems. We conclude by discussing various perspectives, including clinical and therapeutic applications and future directions.