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.
Skinner et al. (Tue,) studied this question.