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Published on: September 13, 2016
Heparin-gelatin mixture improves vascular reconstruction efficiency and hepatic function in bioengineered livers
Kamal Hany Hussein1, Kyung-Mee Park1, Kyung-Sun Kang2
1Stem Cell Institute, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea; Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea; Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
A heparin-gelatin coating promotes endothelial cell attachment and vascularization in decellularized livers, preventing blood clots and enhancing parenchymal cell function for transplantation. This breakthrough advances whole-liver bioengineering for clinical use.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Vascular Biology
Background:
- Whole organ decellularization creates extracellular matrix scaffolds for transplantation but suffers from lack of endothelialization, leading to thrombosis.
- Achieving complete endothelial cell coverage in decellularized organs remains a significant challenge in bioengineering.
Purpose of the Study:
- To investigate the efficacy of a heparin-gelatin (HG) mixture as an antithrombotic coating to enhance endothelial cell (EC) attachment, migration, and vascular network coverage in decellularized liver scaffolds.
- To evaluate the impact of HG-mediated endothelialization on parenchymal cell function and the overall thrombogenicity of the bioengineered liver scaffold.
Main Methods:
- Decellularization of porcine livers using portal vein (PV) perfusion.
- Pre-coating of decellularized vasculature with a heparin-gelatin (HG) mixture.
- Endothelial cell seeding and culture within HG-coated scaffolds in a bioreactor.
- Thrombogenicity assessment via perfusion with porcine blood.
- In vitro co-culture of HepG2 cells and ECs.
- Heterotopic transplantation of scaffolds in pigs.
Main Results:
- HG-precoating significantly improved EC attachment and migration on vascular surfaces.
- ECs efficiently covered the vascular compartments of decellularized scaffolds, maintaining function and proliferation.
- HG-precoated scaffolds demonstrated no thrombosis after 24-hour blood perfusion, indicating successful vascular tree endothelialization.
- HepG2 cell function was enhanced in scaffolds endothelialized after HG-precoating, both in vitro and after in vivo transplantation.
Conclusions:
- Heparin-gelatin coating is an effective strategy for promoting vascularization and preventing thrombosis in decellularized liver scaffolds.
- Enhanced endothelialization improves parenchymal cell function, paving the way for bioengineered liver transplantation.
- This approach represents a significant advancement toward creating clinically applicable, whole-liver tissue engineered constructs.
