Culturing mammalian cells in RGD peptide-modified alginate hydrogel microtubes

Traditional livestock farming is resource-intensive and environmentally unsustainable, highlighting the need for alternative methods of meat production. Cell-cultured meat, produced through the in vitro expansion and differentiation of animal cells, offers a promising solution to supplement conventional meat sources. However, the emerging industry faces a significant challenge - achieving large-scale, cost-effective cell production. In this study, we developed a microbioreactor system based on RGD peptide-modified alginate hydrogel tubes (AlgTubes) to address this challenge. AlgTubes provide a cell-friendly, three-dimensional microenvironment that supports efficient mass transport while minimizing shear stress, thereby significantly enhancing cell viability and yield. This system overcomes key limitations of traditional bioreactors, such as shear-induced cell damage and cell aggregation. Using AlgTubes, we successfully expanded mouse (C2C12) and quail (QM7) myoblasts, achieving cell densities exceeding 1.0 × 10⁸ cells/mL - an order of magnitude higher than those typically attainable in conventional stirred-tank bioreactors. Upon induction, the cells could be differentiated into mature myotubes. Co-culturing myoblasts with stromal cells further improved cell yield. By substantially increasing cell density, AlgTubes can significantly reduce the required culture volume, thereby lowering labor, reagent consumption, equipment usage, facility space, and overall manufacturing costs. This innovative system holds strong potential for enabling the large-scale, economically viable production of cultured meat.