Tunable methacrylated hyaluronic acid‐based hydrogels as scaffolds for soft tissue engineering applications

Abstract

Hyaluronic acid (HA)-based biomaterials have been explored for a number of applications in biomedical engineering, particularly as tissue regeneration scaffolds.Crosslinked forms of HA are more robust and provide tunable mechanical properties and degradation rates that are critical in regenerative medicine; however, crosslinking modalities reported in the literature vary and there are few comparisons of different scaffold properties for various crosslinking approaches. In this study, we offer direct comparison of two methacrylation techniques for HA (glycidyl methacrylate HA [GMHA] or methacrylic anhydride HA [MAHA]). The two methods for methacrylating HA provide degrees of methacrylation ranging from 2.4 to 86%, reflecting a wider range of properties than is possible using only a single methacrylation technique. We have also characterized mechanical properties for nine different tissues isolated from rat (ranging from lung at the softest to muscle at the stiffest) using indentation techniques and show that we can match the full range of mechanical properties (0.35-6.13 kPa) using either GMHA or MAHA. To illustrate utility for neural tissue engineering applications, functional hydrogels with adhesive proteins (either GMHA or MAHA base hydrogels with collagen I and laminin) were designed with effective moduli mechanically matched to rat sciatic nerve (2.47 ± 0.31 kPa). We demonstrated ability of these hydrogels to support three-dimensional axonal elongation from dorsal root ganglia cultures. Overall, we have shown that methacrylated HA provides a tunable platform with a wide range of properties for use in soft tissue engineering. K E Y W O R D Shyaluronic acid hydrogels, hydrogel mechanical characterization, neural tissue engineering, soft tissue engineering

Biofabrication of natural hydrogels for cardiac, neural, and bone Tissue engineering Applications

“…Since light is used to crosslink these hydrogels, they should be photocrosslinkable. For this purpose, hydrogels can be made photocrosslinkable by conjugating acrylamide- or acrylate-based groups to the prepolymer backbone, such as in the case of gelatin methacryloyl (GelMA) [ 22 ] and methacrylate hyaluronic acid (HA) [ 47 ]. A photoinitiator is added to commence the polymerization reaction by forming radicals upon light irradiation.…”

Advanced Strategies for Tissue Engineering in Regenerative Medicine: A Biofabrication and Biopolymer Perspective

“…Other biological properties attributed to HA include anti-inflammation non-immunogenicity. The chemical structure of HA, including a variety of functional groups (carboxyl, hydroxyl and amide groups) allow for it to be easily modified to comply with the requirements of a specific tissue [ 50 ]. HA is able to interact with a number of different cells in order to affect aggregation, proliferation and migration [ 51 ].…”

Construction of functional biliary epithelial branched networks with predefined geometry using digital light stereolithography

“…FG is a component of the ECM that mediates cellular functions such as adhesion, spreading, proliferation, and migration of a variety of cell types, including fibroblasts, endothelial and epithelial cells. C MA and HA MA incorporation provides tunability of mechanical properties via variation of the UV dose and material concentration while still maintaining the essential features of the native biliary epithelial microenvironment 32,33 . The incorporation of FG changes the topology of the extracellular matrix in order to provide a surface for cell adhesion, migration, and matrix remodeling 34 .…”