Stereolithographic printing of ionically-crosslinked alginate hydrogels for degradable biomaterials and microfluidics

Abstract

3D printed biomaterials with spatial and temporal functionality could enable interfacial manipulation of fluid flows and motile cells. However, such dynamic biomaterials are challenging to implement since they must be responsive to multiple, biocompatible stimuli. Here, we show stereolithographic printing of hydrogels using noncovalent (ionic) crosslinking, which enables reversible patterning with controlled degradation. We demonstrate this approach using sodium alginate, photoacid generators and various combinations of divalent cation salts, which can be used to tune the hydrogel degradation kinetics, pattern fidelity, and mechanical properties. This approach is first utilized to template perfusable microfluidic channels within a second encapsulating hydrogel for T-junction and gradient devices. The presence and degradation of printed alginate microstructures were further verified to have minimal toxicity on epithelial cells. Degradable alginate barriers were used to direct collective cell migration from different initial geometries, revealing differences in front speed and leader cell formation. Overall, this demonstration of 3D printing using non-covalent crosslinking may enable adaptive and stimuli-responsive biomaterials, which could be utilized for bio-inspired sensing, actuation, drug delivery, and tissue engineering.

Printability and Shape Fidelity of Bioinks in 3D Bioprinting

“… 247 , 255 Additionally, besides using photo-cross-linking, noncovalently cross-linked alginate hydrogels have also been processed with DLP, via the incorporation of photoacid moieties in the ink formulation, to tune the rate of ionic bonds formation between calcium cations and the anionic alginate chains. 266 …”

Surface Patterning of Hydrogel Biomaterials to Probe and Direct Cell–Matrix Interactions

“…The authors observed that monolayers with an initially convex geometry were pulled forward faster than flat geometries due to supramolecular actomyosin cables ( Figure a). [ 279 ]…”

Modeling Neurovascular Disorders and Therapeutic Outcomes with Human-Induced Pluripotent Stem Cells

“…The next step in the fabrication of a biomimetic in vitro neurovascular model involves integrating the latest advances in iPSC derivation methods along with tissue engineering approaches for generating capillary-sized vascular structures. As opposed to extrusion-based 3D printing, projection stereolithographic printing techniques can produce 3D scaffolds with complex integrated fluidic channels (diameters as small as 20 μm) through spatially controlled cross-linkage of photosensitive prepolymer solution by targeted light exposure, delivered by computer-controlled digital micro-mirror assemblies or through a 2D “mask” in a layer-by layer fashion (Hribar et al, 2015 ; Wang et al, 2015 ; Raman et al, 2016 ; Valentin et al, 2017 ). Laser-assisted printing operates in a similar fashion, except that the laser focus is traditionally “patterned” by CAD file and, in the case of two-photon systems utilizing pulsed femtosecond laser sources, has achieved pattering of hydrogel features as small as 10 μm (Hoffmann and West, 2013 ).…”