Oxidative, Colloidal, and Rheological Failure Modes in HBOCs Under Thermal Cycling: Microvascular Oxygen Flux Analysis

Overview

Hemorrhage remains a leading cause of preventable death in trauma, battlefield injury, obstetric emergencies, and mass casualty events because definitive care is often delayed by limited access to safe, type-matched donor blood. Hemoglobin-based oxygen carriers (HBOCs) could expand emergency oxygen delivery capacity, but deployment is constrained by storage and transport degradation, including hemoglobin autoxidation to methemoglobin (MetHb), aggregation-driven colloidal instability, and rheological drift that collectively reduce oxygen transport. Most HBOC stability evaluations rely on static chemical endpoints, which do not directly quantify the clinically relevant function: oxygen transfer under capillary-scale flow where residence time and diffusion limitations govern delivery. To address this gap, a capillary-scale microvascular flow phantom was constructed and a functional stability metric, the Oxygen Flux Preservation Index (OFPI), was defined as the normalized inlet-to-outlet oxygen transfer capability under standardized flow following controlled deoxygenation. Six 10 g/dL HBOC formulations (pH 7.4) were tested: Hb in PBS (F0), trehalose (F1), sodium ascorbate (F2), EDTA (F3), trehalose plus ascorbate (F4), and trehalose plus ascorbate plus EDTA (F5). Samples were subjected to field-mimicking thermal cycling (4°C → 25°C → 37°C) for 20 days with parallel constant 4°C controls. At Days 0, 3, 7, 10, 14, 17, and 20, OFPI was measured alongside full visible spectra (400–700 nm), MetHb% via spectral deconvolution, oxidation index (A630/A576), aggregation metrics (A700 scattering and dynamic light scattering), pH, and viscosity. Mixed-effects time-course modeling and multivariate regression were applied to quantify OFPI decay kinetics and deconvolve independent oxidative, colloidal, and rheological contributions to functional loss. Thermal cycling caused significantly greater functional decline than constant refrigeration, and multi-mechanism stabilization preserved oxygen flux most effectively, with the trehalose–ascorbate–EDTA formulation maintaining the highest OFPI over 20 days and exhibiting the slowest OFPI decay rate. Regression-based deconvolution demonstrated that OFPI loss was not explained by MetHb% alone, with aggregation and viscosity contributing independent predictive power. These findings establish OFPI as a deployment-relevant functional endpoint and provide a mechanistic framework for designing HBOC formulations that better preserve microvascular oxygen delivery under realistic field stress.

Competition history

• CSEF 2026 Biochemistry/ Molecular Biology (Senior Division) · Entry S-04-01

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