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.

Bioprinting and plastic compression of large pigmented and vascularized human dermo-epidermal skin substitutes by means of a new robotic platform

“…The 3D-printing platform of regenHU offered the necessary technological instrumentation and flexibility to implement our manual protocols in an automated assembly system. The pre-existing platform consisted of a microvalve inkjetting device suitable for printing cells, [47][48][49][50][51][52] for example keratinocytes and melanocytes. We modified the platform by the addition of two new modules for our specific needs to establish the SkinFactory: The first module is made up of a piston-driven extrusion tool, which utilizes a double syringe and a mixer tip for combining collagen and cells (fibroblasts).…”

Printability and Shape Fidelity of Bioinks in 3D Bioprinting

“…The potential of a given bioink to counter gravity can be quantitatively evaluated through printing a filament over a pillar array, bridging a gap at increasing distance, e.g., as previously reported with gap sizes ranging between 1–12 mm and measuring the angle of deflection 78 , 172 or the area below the filament. 42 , 174 The angle of deflection θ, expressed as a function of the gap distance, is a measure of the deformation suffered by the filaments due to the discrepancy between the gravitational force given by the filament’s own weight, and inertia measured by yield stress and storage modulus of the ink. In particular, yield stress was suggested as predictor of potential filament deformation as increasing values for this parameter correlated with lower deflection angle values.…”

“…Poor or slow stabilization of the ink after dispensing, as well as fusion of adjacent filaments are in fact marked by the collapse of the filament circularity. 78 , 174 Semiquantitative evaluation, based on the circularity of printed filaments and shape fidelity of the pore, was recently introduced. 46 , 140 Using this approach, a printability index ( P r ) which is based on the perimeter and area of the pore can be easily derived ( Figure 6 Biii).…”

Engineering bioinks for 3D bioprinting

“…Comparative studies between bioinks loaded with different amounts of nanoparticles demonstrated that they could improve the bioinks mechanical properties. Recently, Lee and colleagues assessed the incorporation of aminopropyl-modified silica nanoparticles into an oxidized alginate bioink [89]. The particles were linked by reversible imine bonds, allowing the creation of a dynamic polymer with thixotropic and self-healing properties.…”