Abstract
Background: Antiphospholipid syndrome (APS) is a major cause of pregnancy morbidity, characterized by antiphospholipid antibody–induced platelet activation and placental thrombosis. Integrin αIIbβ3 is a key mediator of platelet aggregation in this pathological process. Methods: We developed PEGDA-based hydrogels functionalized with acrylated RGD peptides to competitively bind αIIbβ3 and inhibit platelet aggregation. The effects of hydrogel and αIIbβ3 antibody treatments were evaluated in vitro using integrin-binding assays, turbidity-based platelet aggregation and clotting assays, ELISA for cytokine release, and transwell migration of trophoblasts. Results: RGD-modified hydrogels showed dose-dependent binding to αIIbβ3. Both hydrogel and antibody treatments significantly reduced antiphospholipid antibodies (aPL)-induced platelet aggregation, delayed fibrin clot formation, and suppressed IL-6 and TNF-α release from trophoblasts. Cell migration assays confirmed that these interventions preserved trophoblast motility impaired by aPL exposure. Conclusion: Targeting integrin αIIbβ3 with RGD-functionalized biomaterials or neutralizing antibodies effectively attenuated aPL-mediated thromboinflammation. This approach represents a promising localized intervention strategy to prevent APS-related pregnancy complications.
Keywords: Antiphospholipid syndrome; platelet aggregation; integrin α IIbβ 3; RGD-functionalized hydrogel; PEGDA; fibrin clot