Injectable Hydrogel with Slow Degradability Composed of Gelatin and Hyaluronic Acid Cross-Linked by Schiff's Base Formation

Biomacromolecules. 2018 Feb 12;19(2):288-297. doi: 10.1021/acs.biomac.7b01133. Epub 2018 Jan 18.

Abstract

We developed an injectable gelatin/hyaluronic acid hydrogel with slow degradability, which consisted of carbohydrazide-modified gelatin (Gel-CDH) and hyaluronic acid monoaldehyde (HA-mCHO). Gel-CDH/HA-mCHO hydrogels were degraded much more slowly in phosphate-buffered saline than the other Schiff's base cross-linked gelatin/hyaluronic acid hydrogels that were comprised of native gelatin, adipic acid dihydrazide-modified gelatin, or hyaluronic acid dialdehyde because of stable Schiff's base formation between aldehyde and carbohydrazide groups, and suppression of ring-opening oxidation by monoaldehyde modification. This prolonged degradation would be suitable for inducing angiogenesis. Therefore, the Gel-CDH/HA-mCHO hydrogels were sufficiently stable during the angiogenesis process. In addition, the hydrogel had a pore size of 15-55 μm and a shear storage modulus of 0.1-1 kPa, which were appropriate for scaffold application. Ex vivo rat aortic-ring assay demonstrated the concentration dependency of microvascular extension in the Gel-CDH/HA-mCHO hydrogel. These results demonstrated the potential usefulness of Gel-CDH/HA-mCHO hydrogel for tissue-engineering scaffolds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cross-Linking Reagents / chemistry
  • Gelatin / chemistry*
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Hyaluronic Acid / analogs & derivatives*
  • Hydrogels / chemical synthesis
  • Hydrogels / chemistry*
  • Hydrogels / pharmacokinetics
  • Hydrogels / pharmacology
  • Male
  • Neovascularization, Physiologic / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Schiff Bases / chemistry
  • Swine
  • Tissue Scaffolds / chemistry

Substances

  • Cross-Linking Reagents
  • Hydrogels
  • Schiff Bases
  • Gelatin
  • Hyaluronic Acid