Nanocomposite bioink exploits dynamic covalent bonds between nanoparticles and polysaccharides for precision bioprinting

Abstract

The field of bioprinting has made significant recent progress towards engineering tissues with increasing complexity and functionality. It remains challenging, however, to develop bioinks with optimal biocompatibility and good printing fidelity. Here, we demonstrate enhanced printability of a polymer-based bioink based on dynamic covalent linkages between nanoparticles (NPs) and polymers, which retains good biocompatibility. Amine-presenting silica NPs (ca. 45 nm) were added to a polymeric ink containing oxidized alginate (OxA). The formation of reversible imine bonds between amines on the NPs and aldehydes of OxA lead to significantly improved rheological properties and high printing fidelity. In particular, the yield stress increased with increasing amounts of NPs (14.5 Pa without NPs, 79 Pa with 2 wt% NPs). In addition, the presence of dynamic covalent linkages in the gel provided improved mechanical stability over 7 days compared to ionically crosslinked gels. The nanocomposite ink retained high printability and mechanical strength, resulting in generation of centimetre-scale porous constructs and an ear structure with overhangs and high structural fidelity. Furthermore, the nanocomposite ink supported both in vitro and in vivo maturation of bioprinted gels containing chondrocytes. This approach based on simple oxidation can be applied to any polysaccharide, thus the widely applicability of the method is expected to advance the field towards the goal of precision bioprinting.

Supramolecular Biopolymers for Tissue Engineering

“…The reversible imine bonds between amines on the nanoparticles and aldehydes of oxidized alginate lead to significant enhancement of the rheological properties and better printability. The yield stress increased 5.4-fold without compromising the biocompatibility of the bioink when using 2 wt% nanoparticles [182]. Moreover, as stated before, it is preferable to avoid the use of cytotoxic crosslinkers or UV light, which can be damaging to the cells.…”

Guiding Lights: Tissue Bioprinting Using Photoactivated Materials

“…[290][291] The rheological properties of such nanocomposite bioinks can be manipulated to a great extent by controlling the size, concentration of nanoparticles, and more importantly the type of interactions between nanoparticles and polymers. [290][291] The function of these nanoparticles was to serve as a mechanical reinforcement and mechanism to dissipate mechanical energy. 240 Self-healing Bioinks: In an effort to reproduce the flow properties necessary for bioprinting, it is suggested that materials crosslinked with reversible bonds could rapidly self-heal and be a promising strategy for producing extrusion bioprinting materials (Figure 19).…”

Smart Bioinks for the Printing of Human Tissue Models

“…The formation of reversible imine bonds between amines on the nanoparticles and aldehydes of OxA provoked considerably enhanced rheological properties resulting in the generation of porous constructs and an ear structure with overhangs and high structural fidelity. The improvement was mostly due to electrostatic interactions between cationic SiNPs and anionic polysaccharides and was significantly impacted by the size and concentration of the nanoparticles as well as the length of polymer chains [ 62 ]. This study indicates that these interactions should be considered when bioprinting cartilage.…”