Material limitations in blood storage bags: A critical review of packaging-induced deterioration

Blood and plasma storage bags are critical yet materially constrained components of transfusion medicine. The global reliance on plasticized polyvinyl chloride (PVC) containers that is primarily softened with di(2-ethylhexyl) phthalate (DEHP) introduces significant risks, including plasticizer leaching, poor gas barrier properties, and the generation of micro- and nanoplastics, all of which actively accelerate the biochemical and functional degradation of blood products (the “storage lesion”). This review provides a critical, interdisciplinary synthesis of how material deficiencies in current packaging compromise blood safety and quality. We analyze the mechanistic pathways of deterioration, evaluate emerging alternative materials (e.g., non-phthalate plasticizers, multilayer films, cyclic olefin copolymers), and assess advanced concepts such as active scavengers and intelligent sensors. Importantly, this work integrates the emerging concern of micro/nanoplastic contamination into the established framework of packaging-induced damage—a timely and underexplored risk. We highlight that while alternatives like DEHT and DINCH show promising in vitro performance, challenges in scalability, cost, and regulatory complexity hinder widespread adoption. Ultimately, we argue that the future of blood storage lies in a paradigm shift: from passive, degradative containers to active, intelligent preservation systems. This transition will require interdisciplinary innovation, combining high-barrier biocompatible materials with real-time monitoring and frugal design to extend shelf life, enhance transfusion safety, reduce environmental impact, and ensure global equity in healthcare. • Conventional PVC–DEHP blood bags actively contribute to storage lesions via plasticizer leaching, oxidative stress, and poor gas barrier performance. • Packaging-induced deterioration affects all blood components, accelerating protein denaturation, lipid peroxidation, and cellular damage. • Emerging alternatives (multilayer films, cyclic olefin copolymers, non-phthalate plasticizers) show improved biocompatibility and barrier properties but face scalability and cost challenges. • Micro- and nanoplastic release from current and emerging materials remains an unresolved safety concern. • Transitioning to active and intelligent blood packaging systems is critical to extend shelf life, enhance transfusion safety, and reduce environmental impact.