Printability of Methacrylated Gelatin upon Inclusion of a Chloride Salt and Hydroxyapatite Nano‐Particles

Abstract

3D biomaterial printing requires an ink to have suitable printability characteristics, as well as creating a final construct of controllable swelling and stiffness. To tune such properties, the impact of adding different levels of chloride salts (NaCl and CaCl2) and hydroxyapatite nano‐particles (nHA) to a highly concentrated and photo‐crosslinkable methacrylated gelatin (GelMA) is investigated. By adding up to 100 mm CaCl2 or 1.11 m NaCl, the GelMA viscosity decreases from that of control GelMA (no salt). Interestingly, a 25G needle and strong photo‐polymerization kinetics are able to overcome the low viscosity of the 50CaG ink during printing. Adding further CaCl2 increases GelMA viscosity, while decreasing both the swelling and dynamic modulus of the UV‐cured construct observed in water. As all UV‐cured constructs have a dynamic modulus greater than 1 MPa, this novel system is able to match the dynamic modulus of articular cartilage—a feat not previously reported for a GelMA‐based system. Lastly, nHA inclusion improves ink printability, as well as decreases swelling and increases dynamic modulus of the final construct. Overall, this study leads to the successful development of a new advanced functional ink which will be beneficial in the 3D printing of biomaterials toward tissue engineering applications.

A Carbodiimide Coupling Approach for PEGylating GelMA and Further Tuning GelMA Composite Properties

“…As PEG can only bind approximately two water molecules per repeating ethylene oxide unit, [ 18 ] while free carboxyl groups can interact with three or more, [ 19 ] we hypothesized that PEGylation of GelMA would improve the “salting in” effect of GelMA with water such that the water will be more freely available and the capacity of the solution to flow will increase without detectable impact on UV curing kinetics. Similar to that previously observed for control GelMA, [ 5 ] it was also hypothesized that the addition of calcium salt to the aqueous GelMA‐PEG solution would neutralize the zeta potential. Furthermore, swelling of the resultant hydrogel was expected to decrease slightly as PEGylating GelMA reduces the aforementioned attraction of water molecules to bind to available hydration centers on GelMA.…”

“…The control GelMA has previously been reported to have a zeta potential of −9.8 mV (≈95% DS). [ 5 ] Following further modification and loss of free carboxyl groups, the zeta potential of GelMA‐PEG became significantly less negative (−2.4 mV) than the original GelMA ( Figure ).…”

“…The remaining characterization presented in this study addresses the two most significant properties of a GelMA‐based composite toward bone tissue engineering applications—specifically, swelling ( Figure ) and dynamic stiffness. Owing to our prior success in improving the properties of GelMA‐based composites with calcium addition [ 5 ] and TEGDMA incorporation, [ 22 ] these two factors were further explored for the GelMA‐PEG system.…”

“…Of the various chemical processes available, methacrylation at the free and positively charged amines is the most common approach to modify gelatin (and form gelatin methacrylamide or “GelMA”) and results in a material which is negatively charged (≈−9.8 mV). [ 5 ] An approach which modifies the remaining negatively charged carboxylate groups on the GelMA structure may allow for the physicochemical properties of GelMA to be further tuned. For example, Van Hoorick et al.…”

“…[ 20,21 ] In addition, we recently reported on the inclusion of triethyleneglycol dimethacrylate (TEGDMA) in a calcium‐salted GelMA‐nHA composite and the significant gains in mechanical properties as a result. [ 22 ] In this study, the impact of GelMA PEGylation and TEGDMA incorporation on the mechanical and swelling properties of the resultant GelMA‐nHA composites were investigated concurrently. We hypothesized that owing to the drastic decrease in swelling observed upon nHA addition itself, that PEGylation of GelMA would not detectably impact composite swelling.…”