Procyanidins-crosslinked aortic elastin scaffolds with distinctive anti-calcification and biological properties

Acta Biomater. 2015 Apr:16:81-93. doi: 10.1016/j.actbio.2015.01.028. Epub 2015 Jan 30.

Abstract

Elastin, a main component of decellularized extracellular matrices and elastin-containing materials, has been used for tissue engineering applications due to their excellent biocompatibility. However, elastin is easily calcified, leading to the decrease of life span for elastin-based substitutes. How to inhibit the calcification of elastin-based scaffolds, but maintain their good biocompatibility, still remains significantly challenging. Procyanidins (PC) are a type of natural polyphenols with crosslinking ability. To investigate whether pure elastin could be crosslinked by PC with anti-calcification effect, PC was first used to crosslink aortic elastin. Results show that PC can crosslink elastin and effectively inhibit elastin-initiated calcification. Further experiments reveal the possible mechanisms for the anti-calcification of PC crosslinking including (1) inhibiting inflammation cell attachment, and secretion of inflammatory factors such as MMPs and TNF-α, (2) preventing elastin degradation by elastase, and (3) direct inhibition of mineral nucleation in elastin. Moreover, the PC-crosslinked aortic elastin maintains natural structure with high pore volume (1111 μL/g), large pore size (10-300 μm) and high porosity (75.1%) which facilitates recellularization of scaffolds in vivo, and displays excellent hemocompatibility, anti-thrombus and anti-inflammatory potential. The advantages of PC-crosslinked porous aortic elastin suggested that it can serve as a promising scaffold for tissue engineering.

Keywords: Calcification; Crosslinking; Elastin; Procyanidins; Tissue engineering scaffold.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / metabolism*
  • Aorta / ultrastructure
  • Biflavonoids / pharmacology*
  • Blood Coagulation / drug effects
  • Calcification, Physiologic / drug effects*
  • Catechin / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Line
  • Cross-Linking Reagents / pharmacology*
  • Elastin / pharmacology*
  • Glutaral / pharmacology
  • Heart Valves / cytology
  • Heart Valves / drug effects
  • Heart Valves / ultrastructure
  • Hemolysis / drug effects
  • Humans
  • Macrophages / cytology
  • Macrophages / drug effects
  • Matrix Metalloproteinase 12 / metabolism
  • Minerals / metabolism
  • Pancreatic Elastase / metabolism
  • Platelet Adhesiveness / drug effects
  • Porosity
  • Proanthocyanidins / pharmacology*
  • Proteolysis / drug effects
  • Rats, Sprague-Dawley
  • Staining and Labeling
  • Sus scrofa
  • Tissue Scaffolds / chemistry*

Substances

  • Biflavonoids
  • Cross-Linking Reagents
  • Minerals
  • Proanthocyanidins
  • procyanidin
  • Catechin
  • Elastin
  • Pancreatic Elastase
  • Matrix Metalloproteinase 12
  • Glutaral