Marrow-mimicry MEW scaffolds recapitulate erythroblastic islands for high-density cRBC biomanufacturing
- 1The University of Queensland
Abstract
Biomanufactured cell therapies are delivering a step-change in modern medicine, but their high costs have prevented widespread adoption. Cultured red blood cells (cRBCs) are one type of cell therapy in clinical trials for off-the-shelf blood transfusion but remain limited by the exorbitant costs of manufacturing trillions of RBCs required for a blood transfusion. These costs could be mitigated if culture platforms could grow cells at higher density, like those found in the bone marrow, requiring less media and lower concentrations of expensive growth factors per cell. We engineered melt electrowritten (MEW) polycaprolactone (PCL) scaffolds in geometries which imitate marrow trabeculae structures and were then plasma-treated to enable peripheral blood mononuclear cells (PB MNC) attachment. PB MNC monocytes first adhered to the scaffold and rapidly differentiated into CD68+ macrophage-like cells. These macrophage-loaded scaffolds adhered CD71+ erythroblasts, which then grew from 10 to 25% between days 4 and 8 and produced CD235a+ erythroid cells by day 20, under erythrogenic culture conditions. MEW PCL scaffolds in trabecular-like geometries had greater surface area, adhered more macrophages, and generated more erythroblasts than traditional MEW crosshatch geometries. The MEW scaffolds continuously released less-adherent cells to the supernatant, providing a 74% increase in supernatant cell numbers versus liquid suspension controls with identical cell seeding numbers and media volumes. High-cell-density scaffolds exhibited increased metabolism and endogenous production of self-supportive cytokines, which may offer cost-saving opportunities through future media optimisation. This study reports marrow trabeculae-mimetic MEW PCL designs capable of selectively adhering PB MN cells to develop macrophage-coated scaffolds, which provided physical and paracrine support for cRBC production. This high-cell-density culture platform may be useful for future cell therapy biomanufacturing protocols.
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BibTeX
@misc{galeano2026marrowmimicry,
title = {{Marrow-mimicry MEW scaffolds recapitulate erythroblastic islands for high-density cRBC biomanufacturing}},
author = {G. A. Nausa Galeano and S. A. Costa Maia and N. C. Paxton and K. Bisht and Y. Garcia Marin and R. McKinnon and C. M. de Nys and K. Tao and L. Moroni and J. J. Cooper-White and M. A. Woodruff and R. A. Franco and A. R. Murphy and R. E. Griffiths and M. C. Allenby},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.23.761469},
url = {https://www.biorxiv.org/content/10.64898/2026.10.23.761469v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Marrow-mimicry MEW scaffolds recapitulate erythroblastic islands for high-density cRBC biomanufacturing
AU - G. A. Nausa Galeano
AU - S. A. Costa Maia
AU - N. C. Paxton
AU - K. Bisht
AU - Y. Garcia Marin
AU - R. McKinnon
AU - C. M. de Nys
AU - K. Tao
AU - L. Moroni
AU - J. J. Cooper-White
AU - M. A. Woodruff
AU - R. A. Franco
AU - A. R. Murphy
AU - R. E. Griffiths
AU - M. C. Allenby
PY - 2026
DA - 2026/10/23
PB - bioRxiv
DO - 10.64898/2026.10.23.761469
UR - https://www.biorxiv.org/content/10.64898/2026.10.23.761469v1
AB - Biomanufactured cell therapies are delivering a step-change in modern medicine, but their high costs have prevented widespread adoption. Cultured red blood cells (cRBCs) are one type of cell therapy in clinical trials for off-the-shelf blood transfusion but remain limited by the exorbitant costs of manufacturing trillions of RBCs required for a blood transfusion. These costs could be mitigated if culture platforms could grow cells at higher density, like those found in the bone marrow, requiring less media and lower concentrations of expensive growth factors per cell. We engineered melt electrowritten (MEW) polycaprolactone (PCL) scaffolds in geometries which imitate marrow trabeculae structures and were then plasma-treated to enable peripheral blood mononuclear cells (PB MNC) attachment. PB MNC monocytes first adhered to the scaffold and rapidly differentiated into CD68+ macrophage-like cells. These macrophage-loaded scaffolds adhered CD71+ erythroblasts, which then grew from 10 to 25% between days 4 and 8 and produced CD235a+ erythroid cells by day 20, under erythrogenic culture conditions. MEW PCL scaffolds in trabecular-like geometries had greater surface area, adhered more macrophages, and generated more erythroblasts than traditional MEW crosshatch geometries. The MEW scaffolds continuously released less-adherent cells to the supernatant, providing a 74% increase in supernatant cell numbers versus liquid suspension controls with identical cell seeding numbers and media volumes. High-cell-density scaffolds exhibited increased metabolism and endogenous production of self-supportive cytokines, which may offer cost-saving opportunities through future media optimisation. This study reports marrow trabeculae-mimetic MEW PCL designs capable of selectively adhering PB MN cells to develop macrophage-coated scaffolds, which provided physical and paracrine support for cRBC production. This high-cell-density culture platform may be useful for future cell therapy biomanufacturing protocols.
ER -