Development of heparinized and hepatocyte growth factor‐coated acellular scaffolds using porcine carotid arteries

Abstract

Tissue‐engineered blood vessel substitutes have been developed due to the lack of suitable small‐diameter vascular grafts. Xenogeneic extracellular matrix (ECM) scaffolds have the potential to provide an ideal source for off‐the‐shelf vascular grafts. In this study, porcine carotid arteries were used to develop ECM scaffolds by decellularization and coating with heparin and hepatocyte growth factor (HGF). After decellularization, cellular and nucleic materials were successfully removed with preservation of the main compositions (collagen, elastin, and basement membrane) of the native ECM. The ultimate tensile strength, suture strength, and burst pressure were significantly increased after cross‐linking. Pore size distribution analysis revealed a porous structure within ECM scaffolds with a high distribution of pores larger than 10 μm. Heparinized scaffolds exhibited sustained release of heparin in vitro and showed potent anticoagulant activity by prolonging activated partial thromboplastin time. The scaffolds showed an enhanced HGF binding capacity as well as a constant release of HGF as a result of heparin modification. When implanted subcutaneously in rats, the modified scaffolds revealed good biocompatibility with enzyme degradation resistance, mitigated immune response, and anti‐calcification. In conclusion, heparinized and HGF‐coated acellular porcine carotid arteries may be a promising biological scaffold for tissue‐engineered vascular grafts.

Atomic Force Microscopy Lifetime Analysis: An Intuitive Method for Evaluating Receptor Tyrosine Kinase Dimer-Targeting Inhibitors

“…In addition to targeting the receptor MET, blocking HGF/MET signaling by targeting the ligand HGF is also an important way to inhibit tumors. Therefore, heparin, an inhibitor targeting the ligand HGF, was chosen to inhibit the HGF-induced MET dimers (Figure A).…”

The journey of decellularized vessel: from laboratory to operating room

“…As for cross-linking, it can reduce the immunogenicity of grafts mainly due to hindrance of cross-linked fibers ( Luo et al, 2021 ; Cheng et al, 2023 ). By comparing the inflammatory response, cross-linked vascular scaffolds showed milder inflammatory cell infiltration and regular medial arrangement after 4 weeks compared with uncross-linked decellularized scaffolds.…”

“…Consequently, while biocompatible cross-linking agents are employed to enhance mechanical performance, they also serve to delay the degradation of scaffolds in vivo . While the crosslinking or coating increased the extensibility and reduced the stiffness of the material, it was at the cost of reducing the porosity (especially for 10 μm in diameter) which served as channels for the infiltration of regenerated cells ( Wang et al, 2021 ; Cheng et al, 2023 ). Therefore, although a unified evaluation to balance the mechanics and biocompatibility is absent, there is a principle that can be used for reference that sufficient porosity needs to be ensured after cross-linking or coating.…”