Structural and biological investigation of chitosan/hyaluronic acid with silanized-hydroxypropyl methylcellulose as an injectable reinforced interpenetrating network hydrogel for cartilage tissue engineering

Drug Deliv. 2021 Dec;28(1):607-619. doi: 10.1080/10717544.2021.1895906.

Abstract

Cartilage damage continues to pose a threat to humans, but no treatment is currently available to fully restore cartilage function. In this study, a new class of composite hydrogels derived from water-soluble chitosan (CS)/hyaluronic acid (HA) and silanized-hydroxypropyl methylcellulose (Si-HPMC) (CS/HA/Si-HPMC) has been synthesized and tested as injectable hydrogels for cartilage tissue engineering when combined without the addition of a chemical crosslinking agent. Mechanical studies of CS/HA and CS/HA/Si-HPMC hydrogels showed that as Si-HPMC content increased, swelling rate and rheological properties were higher, compressive strength decreased and degradation was faster. Our results demonstrate that the CS and HA-based hydrogel scaffolds, especially the ones with 3.0% (w/v) Si-HPMC and 2.5/4.0% (w/v) CS/HA, have suitable physical performance and bioactive properties, thus provide a potential opportunity to be used for cartilage tissue engineering. In vitro studies of CS/HA and CS/HA/Si-HPMC hydrogels encapsulated in chondrocytes have shown that the proper amount of Si-HPMC increases the proliferation and deposition of the cartilage extracellular matrix. The regeneration rate of the CS/HA/Si-HPMC (3%) hydrogel reached about 79.5% at 21 days for long retention periods, indicating relatively good in vivo bone regeneration. These CS/HA/Si-HPMC hydrogels are promising candidates for tissue compatibility injectable scaffolds. The data provide proof of the principle that the resulting hydrogel has an excellent ability to repair joint cartilage using a tissue-engineered approach.RESEARCH HIGHLIGHTSAn injectable hydrogel based on CS/HA/Si-HPMC composites was developed.The CS/HA/Si-HPMC hydrogel displays the tunable rheological with mechanical properties.The CS/HA/Si-HPMC hydrogel is highly porous with high swelling and degradation ratio.Increasing concentration of Si-HPMC promote an organized network in CS/HA/Si-HPMC hydrogels.Injectable CS/HA/Si-HPMC hydrogels have a high potential for cartilage tissue engineering.

Keywords: CS/HA/Si-HPMC hydrogel; biomedical applications; cartilage repair; chondrocytes; tissue regeneration.

MeSH terms

  • Animals
  • Cartilage / metabolism*
  • Cell Survival
  • Chitosan / chemistry
  • Chondrocytes / metabolism
  • Compressive Strength
  • Drug Stability
  • Extracellular Matrix / metabolism
  • Female
  • Hyaluronic Acid / chemistry
  • Hydrogels / chemistry*
  • Hypromellose Derivatives / chemistry
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Rheology
  • Tissue Engineering / methods*
  • Tissue Scaffolds / chemistry*

Substances

  • Hydrogels
  • Hypromellose Derivatives
  • Hyaluronic Acid
  • Chitosan