Bioinspired Processing: Complex Coacervates as Versatile Inks for 3D Bioprinting

Abstract

3D bioprinting is a powerful fabrication technique in biomedical engineering, which is currently limited by the number of available materials that meet all physicochemical and cytocompatibility requirements for biomaterial inks. Inspired by the key role of coacervation in the extrusion and spinning of many natural materials, hyaluronic acid–chitosan complex coacervates are proposed here as tunable biomaterial inks. Complex coacervates are obtained through an associative liquid–liquid phase separation driven by electrostatic attraction between oppositely charged macromolecules. They offer bioactive properties and facile modulation of their mechanical properties through mild physicochemical changes in the environment, making them attractive for 3D bioprinting. Fine‐tuning the salt concentration, pH, and molecular weight of the constituent polymers results in biomaterial inks that are printable in air and water. The biomaterial ink, initially a viscoelastic fluid, transitions into a viscoelastic solid upon printing due to dehydration (for printing in air) or due to a change in pH and ionic composition (for printing in solution). Consequently, scaffolds printed using the complex coacervate inks are stable without the need for post‐printing processing. Fabricated cell culture scaffolds are cytocompatible and show long‐term topological stability. These results pave the way to a new class of easy‐to‐handle tunable biomaterials for biofabrication.

Effect of Dynamically Arrested Domains on the Phase Behavior, Linear Viscoelasticity and Microstructure of Hyaluronic Acid – Chitosan Complex Coacervates

“…For example, recently, we showed that the 3D printability, and more precisely the shape retention ability, of HA−CHI complex coacervates can be controlled by changing the pH during processing. 10 We observed a higher extent of shape retention as well as slower dynamics at pH values closer to the pKa of the CHI chains and assigned this to the relative insolubility of the chains.…”

“…More specifically, being able to control the liquid-to-solid transition of complex coacervates by (gradual) changes in pH, salt, or other parameters will enable the formation of novel polyelectrolyte materials. For example, recently, we showed that the 3D printability, and more precisely the shape retention ability, of HA–CHI complex coacervates can be controlled by changing the pH during processing . We observed a higher extent of shape retention as well as slower dynamics at pH values closer to the p K a of the CHI chains and assigned this to the relative insolubility of the chains.…”

“…Complex coacervation is a liquid–liquid phase separation formed through electrostatic interactions between oppositely charged polyelectrolytes and the subsequent release of the originally bound counterions and water molecules. , The resulting system consists of a polymer-rich viscoelastic phase, the complex coacervate, in thermodynamic equilibrium with a polymer-poor liquid phase. Complex coacervate materials have found use in a growing number of applications ranging from underwater glues, filtration membranes, fibers, structural materials, 3D printable inks, drug carriers, particulate emulsifiers, and many more. − …”

New insights into protein–polysaccharide complex coacervation: Dynamics, molecular parameters, and applications

“…Reproduced with permission from Khoonkari et al. [ 190 ] (C) Polyacrylic acid–isoprenyl oxy poly(ethylene glycol)/tannic acid coacervate, which has good adhesion and self‐healing capabilities, allowed the skin wound of Sprague–Dawley rats (8 weeks old) to recover well within 14 days. Reproduced with permission from Wang et al.…”

“…Therefore, besides shear‐thinning behavior and fast self‐healing, maintaining the relaxation dynamics of coacervates within a reasonable range is the key to making coacervate materials that both possess acceptable plasticity and structural rigidity. [ 190 ]…”