Dynamically Cross-Linked Double-Network Hydrogels with Matched Mechanical Properties and Ideal Biocompatibility for Artificial Blood Vessels

ACS Appl Mater Interfaces. 2024 Jun 5;16(22):28134-28146. doi: 10.1021/acsami.4c03063. Epub 2024 May 20.

Abstract

Vessel transplantation is currently considered the "gold standard" treatment for cardiovascular disease. However, ideal artificial vascular grafts should possess good biocompatibility and mechanical strength that match those of native autologous vascular tissue to promote in vivo tissue regeneration. In this study, a series of dynamic cross-linking double-network hydrogels and the resultant hydrogel tubes were prepared. The hydrogels (named PCO), composed of rigid poly(vinyl alcohol) (PVA), flexible carboxymethyl chitosan (CMCS), and a cross-linker of aldehyde-based β-cyclodextrin (OCD), were formed in a double-network structure with multiple dynamical cross-linking including dynamic imine bonds, hydrogen bonds, and microcrystalline regions. The PCO hydrogels exhibited superior mechanical strength, good network stability, and fatigue resistance. Additionally, it demonstrated excellent cell and blood compatibility. The results showed that the introduction of CMCS/OCD led to a significant increase in the proliferation rate of endothelial cells seeded on the surface of the hydrogel. The hemolysis rate in the test was lower than 0.3%, and both protein adsorption and platelet adhesion were reduced, indicating an excellent anticoagulant function. The plasma recalcification time test results showed that endogenous coagulation was alleviated to some extent. When formed into blood vessels and incubated with blood, no thrombus formation was observed, and there was minimal red blood cell aggregation. Therefore, this novel hydrogel tube, with excellent mechanical properties, exhibits antiadhesive characteristics toward blood cells and proteins, as well as antithrombotic properties, making it hold tremendous potential for applications in the biomedical and engineering fields.

Keywords: PVA/CMCS; artificial blood vessel; blood compatibility; double-network; hydrogels; β-cyclodextrin.

MeSH terms

  • Animals
  • Biocompatible Materials* / chemical synthesis
  • Biocompatible Materials* / chemistry
  • Biocompatible Materials* / pharmacology
  • Blood Vessel Prosthesis
  • Cell Proliferation / drug effects
  • Chitosan* / analogs & derivatives
  • Chitosan* / chemistry
  • Chitosan* / pharmacology
  • Cross-Linking Reagents / chemistry
  • Hemolysis / drug effects
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Hydrogels* / chemical synthesis
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Materials Testing
  • Platelet Adhesiveness / drug effects
  • Polyvinyl Alcohol* / chemistry
  • beta-Cyclodextrins / chemistry

Substances

  • Hydrogels
  • Chitosan
  • Polyvinyl Alcohol
  • Biocompatible Materials
  • carboxymethyl-chitosan
  • beta-Cyclodextrins
  • betadex
  • Cross-Linking Reagents