Magnetoelastic Cell Monitoring System for Evaluating the Effects of Surface Chemistry on the Performance of Mesenchymal Stem Cell Growth

The recent clinical adoption of cell therapies has increased the need for more efficient, robust, and reproducible manufacturing technologies. Human mesenchymal stromal cells (hMSCs), a major component of the cell and immunotherapeutic market, remain challenging to manufacture at scale because they require surface attachment and are highly sensitive to culture conditions. Although functional layer-by-layer (LbL) coatings can improve adherent culture performance, identifying optimal surface chemistries and physical parameters typically depends on offline, invasive endpoint assays that are time-consuming and provide limited temporal insight. Coupling engineered coatings with real-time, non-destructive sensing could enable continuous monitoring and faster optimization of adherent cell expansion. Here, we evaluate a magnetoelastic sensing platform for real-time tracking of anchorage-dependent cell growth on collagen-based multilayers functionalized with heparin (HEP/COL) or recombinant heparan sulfate (rHS/COL) under both low- and normal-serum culture conditions. Using resonance-derived growth profiles and endpoint nuclear quantification, we found that functional coatings increased hMSC proliferation under low-serum conditions compared with untreated sensor surfaces. In particular, low-sulfation rHS01/COL-coated sensors supported significantly greater bulk hMSC expansion under low-serum conditions, with differences detectable as early as 48 h. This early sensor-predicted advantage was consistent with increased yields observed in rHS01/COL-coated microcarrier cultures by day 5. Across conditions, the coatings primarily improved expansion efficiency rather than increasing the intrinsic proliferation rate. Collectively, these results establish magnetoelastic sensing as a real-time monitoring approach for early screening and optimization of surface-engineered culture systems for cell manufacturing.