1 research outputs found
Targeting Heparin to Collagen within Extracellular Matrix Significantly Reduces Thrombogenicity and Improves Endothelialization of Decellularized Tissues
Thrombosis within small-diameter vascular grafts limits the development
of bioartificial, engineered vascular conduits, especially those derived
from extracellular matrix (ECM). Here we describe an easy-to-implement
strategy to chemically modify vascular ECM by covalently linking a
collagen binding peptide (CBP) to heparin to form a heparin derivative
(CBP–heparin) that selectively binds a subset of collagens.
Modification of ECM with CBP–heparin leads to increased deposition
of functional heparin (by ∼7.2-fold measured by glycosaminoglycan
composition) and a corresponding reduction in platelet binding (>70%)
and whole blood clotting (>80%) onto the ECM. Furthermore, addition
of CBP–heparin to the ECM stabilizes long-term endothelial
cell attachment to the lumen of ECM-derived vascular conduits, potentially
through recruitment of heparin-binding growth factors that ultimately
improve the durability of endothelialization in vitro. Overall, our
findings provide a simple yet effective method to increase deposition
of functional heparin on the surface of ECM-based vascular grafts
and thereby minimize thrombogenicity of decellularized tissue, overcoming
a significant challenge in tissue engineering of bioartificial vessels
and vascularized organs