The endothelial glycocalyx is among the earliest cellular components disrupted during inflammatory vascular injury, where oxidative stress and inflammatory signaling drive endothelial dysfunction. Current therapeutic strategies remain limited in their ability to provide localized protection directly at the endothelial surface. This study presents a cell surface engineering approach using end functionalized synthetic sulfated polymers to mitigate oxidative stress and attenuate inflammatory responses on endothelial surfaces. Linear polyglycerol sulfates modified one-end with a Q-tagged peptide (LPGS-Q) was enzymatically ligated onto cell surfaces via guinea pig liver transglutaminase (gtTGase), forming an endothelial cell glycocalyx mimicking interface with antioxidant and anti-inflammatory activity that emulates key heparan sulfate-like functions. In vitro, LPGS-Q-modified endothelial cells scavenged reactive oxygen species, preserved glycocalyx integrity, reduced IL-6 secretion under TNF-α stimulation, and maintained viability under oxidative stress. LPGS-Q-treated macrophages also exhibited suppressed TNF-α release following M1 polarization, and surface-engineered endothelial cells showed reduced adhesion of activated peripheral blood mononuclear cells, indicating protection against immune-mediated injury. In a vascular injury mouse transplantation model, LPGS-Q treatment was associated with reduced Th1-associated chemokines and a modest increase in IL-10, suggesting systemic immunomodulatory potential. Although histological injury and immune infiltration at day 7 were comparable between groups, CD31 staining showed increased endothelial-associated area in LPGS-Q treated grafts, consistent with decreased endothelial damage or increased endothelial protection. Together, these data support LPGS-Q-based surface engineering as a modular strategy for localized endothelial protection relevant to inflammatory vascular injury states characterized by oxidative stress and glycocalyx disruption, although its in vivo effects are modest under the current experimental conditions.
Luo et al. (Wed,) studied this question.