Bioactive ELP-coated scaffolds enhance cell-material interactions and support osteogenic differentiation

Poly(lactic-co-glycolic acid) (PLGA) scaffolds are widely utilized in tissue engineering for their biodegradability and mechanical robustness; however, their inherent hydrophobicity and bioinert nature often result in poor initial cell attachment, a critical bottleneck for stable tissue integration. In this study, we developed a modular dual-layer surface functionalization strategy that combines a poly-L-lysine (PLL) electrostatic priming layer with a recombinant elastin-like polypeptide featuring RGD and YIGSR motifs (RY-ELP). The sequential PLL/RY-ELP coating significantly enhanced surface wettability without compromising the scaffold's interconnected porous architecture. This bioactive interface supported robust early adhesion and survival of both HEK293 cells (as a model for weak adherence) and human dental pulp stem cells (hDPSCs). Mechanistically, this enhanced interaction was accompanied by the rapid activation of focal adhesion-related signaling pathways, including FAK, paxillin, and ERK, alongside the upregulated expression of integrin β1 and vinculin. Beyond initial survival, the PLL/RY-ELP coating effectively promoted the osteogenic differentiation of hDPSCs, as evidenced by increased osteogenic marker expression (RUNX2, COL1A1, ALPL, SP7, and BGLAP) and superior matrix mineralization. These findings demonstrate that combining electrostatic priming with sequence-defined bioactive motifs offers a versatile and effective approach to overcome the biological limitations of PLGA scaffolds for regenerative medicine.