Extraembryonic tissues play a crucial role in embryonic development and fetal growth and exhibit remarkable biological and biomechanical properties including, pro-angiogenic, anti-inflammatory, immunomodulatory, anti-fibrotic, antimicrobial, and viscoelastic. These characteristics have driven the development of innovative therapies for regenerative medicine applications. Unlike other biological tissues, the mammalian placenta is considered waste material, making it a highly accessible and easily obtainable resource that poses no additional risks to the health of the mother or fetus. Among the several bioactive derivatives, the extracellular matrix (ECM) from placental membranes has been developed as biological scaffolds, powders, hydrogels, and functionalized polymers for a wide variety of clinical applications. Beyond its primary components, (e.g., collagen, glycosaminoglycans, and proteoglycans) the ECM of placental membranes is enriched with numerous growth factors and cytokines embedded within the matrix, further enhancing the complexity of the tissue microenvironment. Thus, placental membrane ECM contains a reservoir of structural and signaling factors that promote a constructive remodeling host response and the formation of site-appropriate functional tissue. Therefore, this broad review aims to correlate placental morphophysiology with its diverse bioactive properties in tissue engineering and regenerative applications, focusing on biomaterials derived from decellularized extraembryonic membrane matrices. Additionally, the latest biotechnological advancements in ECM-derived biomaterials across diverse medical fields will be discussed, highlighting the progress of experimental protocols and therapies, their limitations, and the future directions for clinical applications. STATEMENT OF SIGNIFICANCE: This review highlights the unique and underutilized potential of extraembryonic tissues, particularly placental membranes, as a resource for regenerative medicine. Unlike other biological materials, placental tissues are non-harmful, easily accessible, and abundant, offering a valuable source of bioactive derivatives such as extracellular matrix (ECM), growth factors, and cytokines. These properties make placental ECM ideal for developing biomaterials like scaffolds, hydrogels, and functionalized polymers for diverse clinical applications. By correlating placental morphophysiology with its bioactive properties, this work fills a gap in the literature and presents novel insights into tissue engineering. The review not only underscores the scientific significance of placental ECM in regenerative medicine but also provides a comprehensive overview of recent advancements, experimental protocols, and future directions for clinical use.
