3D Printing of Shear-Thinning Hyaluronic Acid Hydrogels with Secondary Cross-Linking

Abstract

The development of printable biomaterial inks is critical to the application of 3D printing in biomedicine. To print high-resolution structures with fidelity to a computer-aided design, materials used in 3D printing must be capable of being deposited on a surface and maintaining a printed structure. A dual-cross-linking hyaluronic acid system was studied here as a printable hydrogel ink, which encompassed both shear-thinning and self-healing behaviors via guest–host bonding, as well as covalent cross-linking for stabilization using photopolymerization. When either guest–host assembly or covalent cross-linking was used alone, long-term stable structures were not formed, because of network relaxation after printing or dispersion of the ink filaments prior to stabilization, respectively. The dual-cross-linking hydrogel filaments formed structures with greater than 16 layers that were stable over a month with no loss in mechanical properties and the printed filament size ranged from 100 to 500 μm, depending on printing parameters (needle size, speed, and extrusion flux). Printed structures were further functionalized (i.e., RGD peptide) to support cell adhesion. This work highlights the importance of ink formulation and cross-linking on the printing of stable hydrogel structures.

Structured Macroporous Hydrogels: Progress, Challenges, and Opportunities

“…[182] Prestwich and co-workers have reported the combination of thermogelation via gelatin (providing rapid physical gelation once cooled) with UV photopolymerization of pendant methacrylate groups (providing post-reaction stabilization and mechanical enhancement of the printed structure [183] ), while Burdick and co-workers have reported a combination of shear-disruptable host-guest physical interactions (providing rapid gelation once the nozzle shear is relieved) with UV photopolymerization as a 3D printable hydrogel ink capable of supporting cell growth. [184] However, to our knowledge, in situ covalent chemistry has not yet been reported in conjunction with 3D printing, likely attributable to the incompatibility of most current 3D printer designs for enabling the rapid mixing required for printing covalent in situ gelling polymers.…”

Tissue Engineering and Regenerative Medicine: New Trends and Directions—A Year in Review

“…The same group further explored an HA dual-crosslinking hydrogel system (guest-host bonding followed by photopolymerization) to obtain 3D stable structures produced by traditional layer-by-layer deposition approaches. 24 Under optimized conditions, 3D hydrogel structures of reasonable sizes (up to 16 layers) were successfully printed with a high shape fidelity and long-term stability (up to a month of incubation) without needing to use a secondary supporting material.…”

Microscale Architecture in Biomaterial Scaffolds for Spatial Control of Neural Cell Behavior

“…Most biomaterials do not exhibit favorable rheological properties for 3D printing so researchers have transformed the rheological properties of biomaterials by functionalizing them with moieties that form physical crosslinks (Lu et al, 2012a;Shepherd et al, 2012;Ouyang et al, 2016). An example of this involves supramolecular bonding of adamantane and β-cyclodextrin moieties, which assemble into a complex at low stress and disassemble when exposed to high stress (Ouyang et al, 2016).…”

“…An example of this involves supramolecular bonding of adamantane and β-cyclodextrin moieties, which assemble into a complex at low stress and disassemble when exposed to high stress (Ouyang et al, 2016). HA scaffolds were formed using supramolecular bonds by modifying the HA macromer with adamantine and β-cyclodextrin separately, and mixing of the two modified HA solutions together to form the scaffold (Ouyang et al, 2016).…”