Development of Injectable Hydrogel Based on Nanocomposite of Nanocrystalline Cellulose/Chitosan/Pectin for Cartilage TissueEngineering

Background and Aim: Cartilage tissue engineering (CTTE) is proposedas an emerging promising therapeutic strategy that offers advantagesover the current treatment approaches, which seeks to overcome thecartilage self-repair limitation through the development of cellularscaffolds that closely mimic the complex structure of cartilage tissue.Among a variety of biomaterial scaffolds used in CCTE, in situ injectablehydrogel systems are highly desirable for the clinical applications dueto the biocompatibility, highly hydrated 3-D environment similar to thecartilaginous ECM structure, ability to effectively deliver cells and/orbioactive molecules to targeted sites.Methods: About 1.5 g aliquot of pectin was dissolved in 150 mL ofpurified water in a 500 mL flask. A total of 0.8 g of NaIO4 was dissolvedin 10 mL of purified water and added dropwise to the pectin solution.The mixture was allowed to stir for 2 hours at room temperature before0.4 mL of ethylene glycol was added. The solution was dialyzed for 2days. The same procedure was used for the oxidation of cellulose CNCs.Finally, a double-barrel syringe was used to make injectable hydrogelsof chemically cross-linked pectin and CNCs. Barrel A contained a 4 wt% chitosan solution in purified water and barrel B contained a 4 wt %pectin-CHO and CHO-CNC solution. Then, all materials were sterilizedand the polymer solutions at different weight ratios were prepared inthe presence of chondrocytes in a specific medium. Subsequently,chondrocytes were incorporated into the hydrogels and the cell viabilityand proliferation of cells were assessed.Results: In this study, a biomimetic injectable chitosan/pectin hydrogel wasproduced with excellent properties for CTTE scaffold. The hydrogel wasoptimized and showed suitable physicochemical properties, includingthermal stability, compressive strength, viscoelastic behavior, swellingratio, and degradation rate. Having such characteristics, the hydrogelmeet the requirements for the cartilage repair. The hydrogel precursorsand cross-linked hydrogels were thoroughly characterized regarding theirchemical, morphological, microstructural and mechanical properties, aswell as their swelling and degradation profiles. The hydrogels provideda host tissue-mimetic microenvironment for maintaining chondrocytephenotype. Conclusion: Altogether, we successfully prepared the biomimeticinjectable hydrogel without incorporating any extraneous cross-linkingagents under physiological conditions. The properties of the hydrogelsuch as gelation time, mechanical properties and degradation behavior,were easily adjusted. When chondrocytes were encapsulated intohydrogels, it was found that cell behavior was remarkably affected byCS/pectin composition. The in-vitro study showed that the incorporationof chondrocytes to the hydrogel was able to maintain long-termchondrocytes survivability and improve cartilaginous ECM deposition.We believe the biomimetic injectable hydrogel based on polysaccharidesis very promising scaffolds for CTTE application.

Keywords:

Injectable hydrogels , Adipose-derived stem cells , Cartilage tissue engineering