Cellular aggregate formation: Continuum modelling and computational aspects
Soheil Firooz,
B. Daya Reddy,
Vasily Zaburdaev,
Paul Steinmann
Computer Methods in Applied Mechanics and Engineering
451
118687
(2026)
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In this manuscript, we carry out a systematic study on the mechanics and rheology of cellular aggregate formations. We study how cell–cell and cell–matrix interactions influence cellular aggregation, which can be described as an active phase separation process. Furthermore, we investigate the mechanisms underlying the coalescence of aggregates. The problem is analyzed in both Eulerian and Lagrangian frameworks and the computational intricacies for each approach are highlighted. Using our recently developed micromorphic-based artificial diffusion method, we circumvent the numerical instabilities arising from the convective nature of the problem. Finally, via a comprehensive numerical study, we investigate the dynamics of the cellular aggregate formation under various conditions. A notable agreement between the numerical and experimental results is observed. Our work provides significant insights into the mechanics of cellular aggregates which paves the way for better understanding the role of active mechanical forces in biological systems.
Red Blood Cell-derived Extracellular Vesicles as biomaterials: the opportunity of freezing-induced accelerated aging
Lucia Paolini,
Miriam Romano,
Valentina Mangolini,
Selene Tassoni,
Shuhan Jiang,
Elena Laura Mazzoldi,
Angelo Musicò,
Andrea Zendrini,
Anna Kashkanova, et al.
Biomaterials Science
14
122-139
(2026)
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Red blood cell-derived extracellular vesicles (RBC-EVs) are emerging as promising biomaterials for next-generation drug delivery, owing to their intrinsic biocompatibility, immune evasion properties, and minimal oncogenic risk. However, their broader application is currently limited by unresolved challenges related to heterogeneity, reproducibility, and long-term storage stability. By combining discontinuous sucrose density gradient separation with high-resolution interferometric nanoparticle tracking analysis, we identified a sharp bimodal size distribution of the vesicles in freshly prepared samples. We then tracked how long-term storage at −80 °C drove its conversion into a monomodal distribution. To reproduce these conditions in a shorter time frame, we developed an “accelerated-ageing” protocol based on freeze–thaw cycles that generates RBC-EV samples with homogeneous density, size distribution, and biological activity, effectively replicating the properties of preparations stored for six months at −80 °C. This new vesicle population results stable and retains membrane integrity and cellular internalization capacity, as confirmed by surface-associated enzymatic activity assays and uptake tests in cancer cell lines. These results suggest that freezing-induced “accelerated ageing” represents an effective method for the optimization and standardization of RBC-EVs as building blocks for biomaterial and bioengineering applications.
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