From phthalates to microplastics: Emerging and unresolved biocompatibility risks in extracorporeal circulation

Abstract

Background

Extracorporeal circulation (ECC) is increasingly supported by biomaterials engineered to minimize chemical leaching, and many biomedical manufacturers have now removed or substantially reduced phthalate plasticizers particularly di(2-ethylhexyl) phthalate (DEHP) from tubing and circuit components. Nevertheless, emerging evidence highlights a parallel and underexplored concern: the generation of microplastic particles, especially during manual cutting and customization of circuit segments in the operating room. While screen and depth filters used in CPB and ECMO circuits efficiently remove particles above defined size thresholds, the fate of smaller microplastics potentially capable of transiting through current filtration systems remains largely unknown. This raises new biocompatibility questions in an area where evidence is sparse and risk assessment remains incomplete.

Materials and methods

A structured narrative review was conducted using PubMed and Web of Science, supplemented by manual reference screening. Search terms included “phthalates,” “DEHP-free circuits,” “microplastics,” “extracorporeal circulation,” “cardiopulmonary bypass,” “ECMO,” “biomaterials,” and “particle shedding.” Studies published between 1989 and 2025 addressing chemical migration, particulate release, biomaterial–blood interactions, or clinical exposure were eligible. After screening titles, abstracts, and full texts, 15 relevant studies were identified and included for qualitative synthesis.

Results

Across included studies, phthalate reduction strategies such as the adoption of DEHP-free materials (e.g., TOTM-based tubing) demonstrably decreased chemical migration during ECC. However, the shift toward alternative materials does not preclude the mechanical generation of microplastic particles. Evidence from biomaterial studies suggests that shear stress, handling, and intraoperative cutting may contribute to particulate release. Unlike phthalates, microplastic contamination has not been systematically quantified in ECC settings, and current filters are optimized for macro- and microdebris but not necessarily for sub-micron or small-microplastic fractions. This gap contrasts with the well-characterized exposure profiles of phthalates, leaving the particulate dimension of ECC biocompatibility largely uncharted. Preliminary mechanistic data indicate that microplastics may act as carriers for residual plasticizers or other adsorbed molecules, potentially amplifying biological interactions.

Conclusions

Although phthalate exposure has decreased with industry-wide adoption of alternative plasticizers, microplastic release particularly from manual circuit preparation represents an emerging and insufficiently characterized risk in ECC. Existing filtration technologies may not capture the smallest particles, and no standardized monitoring or exposure-reduction protocols currently address this issue. These findings underscore critical knowledge gaps and highlight the need for targeted research on microplastic generation, trans-filter passage, biological effects, and mitigation strategies. Open questions regarding particulate contamination challenge the current definition of biocompatibility and call for a broadened translational framework to ensure safer extracorporeal technologies.