A one-step surface engineering strategy based on PEG-EGCG to improve systemic delivery and survival of transplanted mesenchymal stromal cells

The intravenous delivery of mesenchymal stromal cells (MSCs) is often limited by pulmonary entrapment and poor survival under oxidative stress in inflammatory environments. To overcome these challenges, a multifunctional cell-surface engineering strategy driven by the synergistic coordination of polyethylene glycol (PEG), epigallocatechin gallate (EGCG), and magnesium (Mg 2+ ) was adopted in this study. PEG and EGCG were first covalently coupled to form the polymer, PEG-EGCG, in which PEG provides “stealth” shielding, and EGCG facilitates mild membrane insertion and Mg 2+ coordination. The resulting PEG-EGCG–Mg complex self-assembled on MSCs, forming a stealth layer and a metal–phenolic network. This P-E-Mg@MSCs design significantly reduced cell adhesion to endothelium and collagen, thereby diminishing pulmonary trapping and leading to increased bone marrow accumulation in a murine model of immune-mediated aplastic anemia (AA). Furthermore, the coating conferred potent antioxidant and anti-inflammatory properties, thereby improving MSC survival under oxidative stress. In AA mice, treatment with P-E-Mg@MSCs restored peripheral blood counts, reduced bone marrow adiposity, and modulated immune imbalance by upregulating regulatory T cells and downregulating cytotoxic CD8 + T cells, thereby outperforming unmodified MSCs. This work presents a versatile coating platform that integrates adhesion inhibition, microenvironment modulation, and metal-ion coordination to enhance the systemic delivery and therapeutic efficacy of MSCs for regenerative and immunomodulatory applications.