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

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 HIGHLIGHTS An 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.

Advanced Hydrogels for Cartilage Tissue Engineering: Recent Progress and Future Directions

“…They are usually formed using different crosslinking methods and agents to solely crosslink one type of polymers within the network. Therefore, a network of independently crosslinked polymers are created that shows improved mechanical properties compared with their single-component network counterparts [ 116 ]. Generally, the primary polymeric network is made of flexible and elastic materials compared with the secondary network, which is stiffer and more brittle in relatively lower concentration [ 115 , 116 ].…”

“…Therefore, a network of independently crosslinked polymers are created that shows improved mechanical properties compared with their single-component network counterparts [ 116 ]. Generally, the primary polymeric network is made of flexible and elastic materials compared with the secondary network, which is stiffer and more brittle in relatively lower concentration [ 115 , 116 ]. Schipani et al studied mechanically reinforced IPN hydrogels of alginate and gelatin methacryloyl (GelMA) reinforced by polycaprolactone (PCL) fibers.…”

Hydrogel, Electrospun and Composite Materials for Bone/Cartilage and Neural Tissue Engineering

“…To sum up, despite their many advantages, hydrogels might show various stability and gelation times in vitro and in vivo [108]. Additionally, most hydrogels, especially synthetic ones, characterize biological inertia due to a lack of sites that effectively bind cells with material, resulting in decreased adhesion and proliferation [109]. The hydrogels are also unstable in physiological conditions, resulting in faster than expected degradation in vivo.…”

Ethyl Cellulose and Hydroxypropyl Methyl Cellulose Blended Methotrexate-Loaded Transdermal Patches: In Vitro and Ex Vivo

“…It is widely used in controlled-release formulations due to its swelling, gelling and thickening properties. Furthermore, HPMC is nontoxic in nature, and its swelling and easy compression properties make it convenient for use in the preparation of controlled drug delivery systems [19].…”