The extracellular matrix as an integrator of multisystem adaptation in preterm infants

Abstract

Preterm birth remains a leading cause of neonatal morbidity, mortality, and long-term complications. Contemporary understanding of prematurity pathogenesis increasingly centers on the concept of multisystem maladaptation, with the extracellular matrix (ECM) serving as a key mediator. Historically viewed as a structural connective tissue component, the ECM is now recognized as a dynamic signaling system regulating cell proliferation, differentiation, mechanotransduction, intercellular communication, and tissue remodeling. Aim. This review aims to synthesize current evidence on the role of the extracellular matrix in multisystem adaptation and compensation in preterm infants and to analyze the main mechanisms of ECM remodeling in the development of neonatal and early childhood pathologies. This narrative review incorporated experimental and clinical studies published from 2021 to 2026 across PubMed, Scopus, Web of Science, and the Cochrane Library. Recent studies on matrix biology, mechanobiology, neonatal inflammation, and ECM-associated biomarkers were analyzed. It was established that structural and signaling disturbances in the ECM are associated with the development of bronchopulmonary dysplasia, cerebral damage, vascular dysfunction, necrotizing enterocolitis, and other prematurity- related complications. Oxidative stress, systemic inflammation, hyperoxia, and mechanical ventilation have been identified as key triggers of pathological matrix remodeling. Emerging directions in modern neonatology include ECM-associated biomarkers, proteomic technologies, extracellular vesicles, and ECM-targeted therapy.The extracellular matrix should be regarded as the central integrator of multisystem adaptation in preterm infants and a promising platform for personalized prediction, prevention, and treatment of prematurity- related complications.