Viscoelasticity of hyaluronic acid‐gelatin hydrogels for vocal fold tissue engineering

Abstract

Cross-linked injectable hyaluronic acid-gelatin hydrogels have remarkable viscoelastic and biological properties for vocal fold tissue engineering. Patient-specific tuning of the viscoelastic properties of this injectable biomaterial could improve tissue regeneration. The frequency-dependent viscoelasticity of cross-linked hyaluronic acid-gelatin hydrogels was measured as a function of the concentration of hyaluronic acid, gelatin, and cross-linker. Synthetic extracellular matrix hydrogels were fabricated using thiol-modified hyaluronic acid and gelatin, and cross-linked by Poly(ethylene glycol)diacrylate. A recently developed characterization method based on Rayleigh wave propagation was used to quantify the frequency-dependent viscoelastic properties of these hydrogels, including shear storage and loss moduli, over a broad frequency range; i.e., from 40 to 4000 Hz. The viscoelastic properties of the hydrogels increased with frequency. The storage and loss moduli values and the rate of increase with frequency varied with the concentrations of the constituents. The range of the viscoelastic properties of the hydrogels was within that of human vocal fold tissue obtained from in vivo and ex vivo measurements. Frequency-dependent parametric relations were obtained using a linear least-squares regression. The results are useful to better fine-tune the storage and loss moduli of hyaluronic acid-gelatin hydrogels by varying the concentrations of the constituents for use in patient-specific treatments.

Gelatin‐polysaccharide composite scaffolds for 3D cell culture and tissue engineering: Towards natural therapeutics

“…HA has also been combined with GelMA, providing a robust and decent candidate for 3D cell culture due to its ability to form a composite network after a mild photocrosslinking . The combination of GelMA and methacrylated HA improved the mechanical properties of the composite hydrogels . Furthermore, the physical and biological properties of the combined gels were tunable via changing the composition.…”

“…41 The combination of GelMA and methacrylated HA improved the mechanical properties of the composite hydrogels. [255][256][257] Furthermore, the physical and biological properties of the combined gels were tunable via changing the composition. Interestingly, in the absence of GelMA, the HUVECs did not show any spreading in the 3D hydrogels, highlighting the importance of the synergistic action in polysaccharide-gelatin biomaterials.…”

Tissue engineering-based therapeutic strategies for vocal fold repair and regeneration

“…Mongeau and coworkers measured the viscoelastic properties of Carbylan-GSX hydrogels over a wide range of high frequencies (40–4000Hz) using a Rayleigh wave propagation method, and the storage and loss moduli were easily modulated by tuning gelatin concentrations to be within the range of mechanics of human VF tissues obtained from in vivo and ex vivo measurements. [82–84] The Thibeault group evaluated in vitro cytocompatibility of this matrix by culturing an immortalized human vocal fold fibroblast (hVFF) cell line in two-dimensional and three-dimensional conditions and cell viability, morphology, proliferation, apoptosis, transcript gene expression, and inflammatory markers were measured. In 2D culturing system, immortalized hVFFs developed typically stretched, spindle-like fibroblast morphology similar to those seeded on the surface of polystyrene.…”

Investigation of Chitosan-glycol/glyoxal as an Injectable Biomaterial for Vocal Fold Tissue Engineering

“…Hyaluronic acid is a non-sulfated glycosaminoglycan and a major contributor to maintain VF tissue viscosity. The HA-Ge hydrogels cross-linked by disulfide bond formation are biocompatible [7] and has viscoelastic properties similar to VFLP [8]. The injection of HA-Ge hydrogels in rabbits after unilateral injury resulted in less fibrotic tissue.…”