Improving Host Response to Decellularized Cardiovascular Implants: The Immunomodulatory Potential of Fibronectin and Stromal Cell-Derived Factor 1-Alpha

All articles of this category (opens in new window) Background: The clinical application of decellularized cardiovascular implants is limited by suboptimal host integration and immunomodulatory responses. Successful integration requires a balanced immune reaction and efficient cellular repopulation. While cell repopulation is crucial, graft integration also depends on controlled immune modulation. This study investigates the role of fibronectin (FN), an extracellular matrix protein, and stromal cell-derived factor 1-alpha (SDF1-α), a chemokine involved in cell recruitment and tissue repair, in improving host response to decellularized aortic valve scaffolds. Methods: The immunomodulatory effects of FN/SDF1-α coating of decellularized aortic valve conduits were analyzed in vitro and in vivo. Rat bone marrow-derived macrophages were cultivated with FN/SDF1-α-coated and noncoated ovine decellularized cusps, assessing cell migration, infiltration, cytokine secretion, and gene expression. Furthermore, FN/SDF1-α-coated and noncoated decellularized allogeneic conduits were implanted in an ovine large-animal model. Early immune cell infiltration and repopulation were evaluated within 2 weeks in vivo by (immuno-) histology. Results: FN/SDF1-α coating of decellularized scaffolds was confirmed via immunofluorescence. In vitro, IL-6 secretion in response to decellularized cusps, independent of coating, was insignificant compared with the LPS-stimulated control at 3,221 pg/mL ( p < 0.0001), suggesting minimal pro-inflammatory activation. In contrast, functional assays demonstrated a trend toward enhanced macrophage migration into FN/SDF1-α-coated cusps compared with uncoated matrices. The first FN/SDF1-α-coated allogeneic conduits were successfully implanted in an ovine large-animal model and are currently being analyzed for early repopulation and immune activation compared with noncoated controls. Conclusion: In this study, we successfully coated decellularized aortic valve conduits with FN/SDF1-α and implanted them in an ovine large-animal model. Our data suggest that FN/SDF1-α-coated conduits do not trigger strong inflammatory signaling in vitro, supporting their potential safety in clinical applications. Moreover, FN/SDF1-α coating tends to enhance macrophage recruitment, a key step in scaffold remodeling and tissue integration. These findings indicate that targeted surface modification of decellularized grafts could help overcome current limitations in cardiovascular tissue engineering, potentially leading to implants with better durability, reduced immune rejection, and faster functional integration in patients. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany