3D Bioprinting of Architected Hydrogels from Entangled Microstrands

Abstract

31Hydrogels are an excellent biomimetic of the extracellular matrix and have found great 32 use in tissue engineering. Nanoporous monolithic hydrogels have limited mass transport, 33 restricting diffusion of key biomolecules. Structured microbead-hydrogels overcome some 34 of these limitations, but suffer from lack of controlled anisotropy. Here we introduce a 35 novel method for producing architected hydrogels based on entanglement of microstrands. 36 The microstrands are mouldable and form a porous structure which is stable in water. 37 Entangled microstrands are useable as bioinks for 3D bioprinting, where they align during 38 the extrusion process. Cells co-printed with the microstrands show excellent viability and 39 augmented matrix deposition resulting in a modulus increase from 2.7 kPa to 780.2 kPa 40 after 6 weeks of culture. Entangled microstands are a new class of bioinks with 41 unprecedented advantages in terms of scalability, material versatility, mass transport, 42 showing foremost outstanding properties as a bioink for 3D printed tissue grafts. 43 44 45 46 47 48 49 50 129 130 131 Results 132 133 Entangled Microstrand Materials are Mouldable, Stable in Water and Macroporous 134 135Here we report on a robust and versatile method for preparing 'entangled' microstrands. 136 Bulk hyaluronan-methacrylate (HA-MA) hydrogels were mechanically pressed through a 137

Guiding Lights: Tissue Bioprinting Using Photoactivated Materials

“…[311][312] Kessel et al showed that elongated gel microstands were also applicable to extrusion bioprinting (Figure 19). 313 High-aspect ratio HA-MA microstrands entangled, producing a printed construct with greater stability compared to spherical granular gels. The microstrand constructs did not need to be secondarily crosslinked and the properties of the printed bioink could be adjusted by the time of exposure of the bulk gel to UV light.…”

“…An added advantage is the alignment of the microstrands along the printing direction which contributed to the formation of anisotropic structures and alignment of cells. 313 The mechanism of shear thinning in the nozzle of extrusion printers using entangled inks is illustrated in Figure 21, along with our current understanding of how molecules, nanoparticles, and microgels align and/or deform during flow. In each of these examples, stabilization of the structures by photo-activated materials can be advantageous.…”

“…Despite these limitations, extrusion bioprinting has unique advantages compared to its competitors. It is the only biofabrication technique which can create truly anisotropic properties 313 , as the flow of the material can be used to effectively align fibrils, microgels, and by implication, cells. To benefit from this phenomenon, non-planar slicing software 335 and curvilinear printing 336 could be harnessed to exploit the natural anisotropy of tissues or organs, replacing arbitrary layer-by-layer slicing.…”

Hydrogel‐Based 3D Bioprinting for Bone and Cartilage Tissue Engineering

“…Among these forms, hydrogels are the most applicable and injectable forms of scaffolds in 3D bioprinting owing to their cell‐encapsulating capability and good biocompatibility. [ 95 ] Cells and morphogens can be loaded within the hydrogel solution prior to the gelling via curing agents and through alternations in pH, ionic concentration, and temperature. [ 73 ] As previously discussed, there are two types of hydrogels: natural and synthetic based on their origins.…”

Injectable, Pore‐Forming, Perfusable Double‐Network Hydrogels Resilient to Extreme Biomechanical Stimulations

“…Such hydrogels have been developed in previous studies using either porogen, [ 14,15 ] leachable particles, [ 16 ] nanoclay, [ 17 ] granular particles, [ 18 ] self‐assembly, [ 19,20 ] or polymer degradation. [ 21 ] Bioprintable pore‐forming formulas, such as aqueous two‐phase emulsion system [ 12,22,23 ] and hydrogel microstrands, [ 24 ] could be used for injection as well. These hydrogels, however, suffer from limited pore size and low interconnectivity, which impair permeability and performance.…”