Nanoengineered Ionic–Covalent Entanglement (NICE) Bioinks for 3D Bioprinting

Abstract

We introduce an enhanced nanoengineered ionic-covalent entanglement (NICE) bioink for the fabrication of mechanically stiff and elastomeric 3D biostructures. NICE bioink formulations combine nanocomposite and ionic-covalent entanglement (ICE) strengthening mechanisms to print customizable cell-laden constructs for tissue engineering with high structural fidelity and mechanical stiffness. Nanocomposite and ICE strengthening mechanisms complement each other through synergistic interactions, improving mechanical strength, elasticity, toughness, and flow properties beyond the sum of the effects of either reinforcement technique alone. Herschel-Bulkley flow behavior shields encapsulated cells from excessive shear stresses during extrusion. The encapsulated cells readily proliferate and maintain high cell viability over 120 days within the 3D-printed structure, which is vital for long-term tissue regeneration. A unique aspect of the NICE bioink is its ability to print much taller structures, with higher aspect ratios, than can be achieved with conventional bioinks without requiring secondary supports. We envision that NICE bioinks can be used to bioprint complex, large-scale, cell-laden constructs for tissue engineering with high structural fidelity and mechanical stiffness for applications in custom bioprinted scaffolds and tissue engineered implants.

Copolymer/Clay Nanocomposites for Biomedical Applications

“…Various nanoclays have been employed for the development of copolymer nanocomposites using solution blending, melt mixing, electrospinning and 3D biofabrication yielding films, fiber mesh scaffolds, hydrogels and 3D constructs. (Individual parts reproduced with permission: [ 52 ] Copyright 2016, American Chemical Society (ACS); [ 59 ] Copyright 2014, ACS; [ 60 ] Copyright 2012, ACS; [ 61 ] Copyright 2014, Wiley‐VCH; [ 62 ] Copyright 2018, ACS; [ 63 ] Copyright 2018, ACS; [ 64 ] Copyright 2018, ACS; [ 65 ] Copyright 2018, ACS; [ 66 ] Copyright 2016, Royal Society of Chemistry (RSC); [ 67 ] Copyright 2010, RSC; [ 5a ] Copyright 2015, IOP Publishing; [ 68 ] Copyright 2018, Wiley‐VCH).…”

“…The cells were evenly distributed throughout the constructs. In another study, nanoengineered ionic‐covalent entanglement (NICE) bioinks comprising laponite/gelatin methacryloyl (GelMA) blended with κCA were developed for the fabrication of mechanically stiff and elastomeric 3D biostructures such as bifurcated vessels, and a human ear with 150 layers [ 64 ] as shown in Figure 8b. Mice preosteoblast containing biostructures were flexible, showed excellent compression strength and long term cell viability with greater spreading throughout 121 days of culture compared to that of control hydrogels (without laponite).…”

From Shape to Function: The Next Step in Bioprinting

“…Without functionalization [37] Temperature-triggered gelation Biologically inert Often used as sacrificial material [37] Not suitable for long-term cell culture Diacrylated [93] Radical (photo-) polymerization Without functionalization [83,94] Physically crosslinked Blended with other bioink components (e.g., kappacarrageenan and GelMA [95] Used to modulate the viscosity of an ink to improve printability Can improve cell adhesion and response [96][97][98] Glycerol C 3 H 8 O 3 Viscous and hygroscopic liquid Backbone of many lipids…”

Additive Manufacturing of Precision Biomaterials

“…In AM, this paradigm has been exploited to make bioinks based on the combination of 2D nanosilicates (Laponite) and poly(ethylene glycol) (PEG) . This concept was extended to design nanoengineered ionic‐covalent entanglement (NICE) bioinks that are formed via a nanocomposite of Laponite, ionically cross‐linked kappa‐carrageenan and covalently cross‐linked methacryloyl gelatin (GelMA) for soft tissue bioengineering . Recently, ionic interactions between cationic silica nanoparticles and ionic biopolymers were used to reinforce alginate:gellan bioinks .…”

“…[80] This concept was extended to design nanoengineered ionic-covalent entanglement (NICE) bioinks that are formed via a nanocomposite of Laponite, ionically cross-linked kappa-carrageenan and covalently crosslinked methacryloyl gelatin (GelMA) for soft tissue bioengineering. [81] Recently, ionic interactions between cationic silica nanoparticles and ionic biopolymers were used to reinforce alginate:gellan bioinks. [82] While alginate:gellan bioinks are already used for biofabrication, the nanocomposite improved print fidelity and mechanical properties of the final parts.…”