Self-recovering dual cross-linked hydrogels based on bioorthogonal click chemistry and ionic interactions

J Mater Chem B. 2020 Jul 15;8(27):5912-5920. doi: 10.1039/d0tb01042a.

Abstract

The biocompatible, injectable and high water-swollen nature of hydrogels makes them a popular candidate to imitate the extracellular matrix (ECM) for tissue engineering both in vitro and in vivo. However, commonly used covalently cross-linked hydrogels, despite their stability and tunability, are elastic and deteriorate as bulk material degrades which would impair proper cell function. To improve these deficiencies, here, we present a self-recovering cross-linked hydrogel formed instantaneously with functionalized poly(ethylene glycol) as a basis. We combine covalent cross-links introduced via a strain-promoted azide-alkyne cycloaddition (SPAAC) click reaction and non-covalent links between phosphonate groups and calcium ions. By adjusting the ratios of non-covalent and covalent cross-links, we synthesized these dual cross-linked (DC) hydrogels that displayed storage moduli below ∼2000 Pa and relaxation times from seconds to minutes. The gels recovered to 41-96% of their initial mechanical properties after two subsequent strain failures. Cryo-scanning electron microscopy revealed that DC hydrogels containing approximately equal amounts of covalent and non-covalent cross-links displayed phase separation. Finally, we functionalized the DC hydrogels by incorporating an integrin binding motif, RGDS, to provide a biocompatible environment for human mesenchymal stem cells (HMSCs) by facilitating adhesion inside the gel network. Inside these DC gels HSMCs displayed a viability up to 73% after five days of cell culture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry*
  • Azides / chemistry*
  • Biocompatible Materials / chemistry*
  • Biocompatible Materials / metabolism
  • Calcium / chemistry
  • Cations, Divalent / chemistry
  • Cell Proliferation
  • Cells, Cultured
  • Click Chemistry
  • Cross-Linking Reagents / chemistry
  • Cycloaddition Reaction
  • Extracellular Matrix / metabolism
  • Humans
  • Hydrogels / chemistry*
  • Hydrogels / metabolism
  • Mechanical Phenomena
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Oligopeptides / chemistry
  • Organophosphonates / chemistry
  • Polyethylene Glycols / chemistry*
  • Polyethylene Glycols / metabolism
  • Rheology
  • Tissue Engineering
  • Tissue Scaffolds / chemistry*

Substances

  • Alkynes
  • Azides
  • Biocompatible Materials
  • Cations, Divalent
  • Cross-Linking Reagents
  • Hydrogels
  • Oligopeptides
  • Organophosphonates
  • Polyethylene Glycols
  • arginyl-glycyl-aspartyl-serine
  • Calcium