3D Bioprinting of Macroporous Materials Based on Entangled Hydrogel Microstrands

Abstract

Hydrogels are excellent mimetics of mammalian extracellular matrices and have found widespread use in tissue engineering. Nanoporosity of monolithic bulk hydrogels, however, limits mass transport of key biomolecules. Microgels used in 3D bioprinting achieve both custom shape and vastly improved permissivity to an array of cell functions, however spherical‐microbead‐based bioinks are challenging to upscale, are inherently isotropic, and require secondary crosslinking. Here, bioinks based on high‐aspect‐ratio hydrogel microstrands are introduced to overcome these limitations. Pre‐crosslinked, bulk hydrogels are deconstructed into microstrands by sizing through a grid with apertures of 40–100 µm. The microstrands are moldable and form a porous, entangled structure, stable in aqueous medium without further crosslinking. Entangled microstrands have rheological properties characteristic of excellent bioinks for extrusion bioprinting. Furthermore, individual microstrands align during extrusion and facilitate the alignment of myotubes. Cells can be placed either inside or outside the hydrogel phase with >90% viability. Chondrocytes co‐printed with the microstrands deposit abundant extracellular matrix, resulting in a modulus increase from 2.7 to 780.2 kPa after 6 weeks of culture. This powerful approach to deconstruct bulk hydrogels into advanced bioinks is both scalable and versatile, representing an important toolbox for 3D bioprinting of architected hydrogels.

The rheology of direct and suspended extrusion bioprinting

“…Chondrocytes seeded outside the gel microstrands had comparable viability and formed a cartilage-like tissue matrix with a compressive modulus approximately 50% of the native tissue strength by 42 days. 113 …”

3D Printing of Strong and Tough Double Network Granular Hydrogels

“…[34][35][36][37] However, monodisperse spherical microgels have a small contact area such that the resulting superstructures are weak. [38] The mechanical properties of these granular materials can be improved if the surfaces of the microgels are modified with thiols [39] or metal-coordinating groups, [40] through covalent crosslinking of adjacent microgels, [41] or by means of a percolating second network. [42,43] However, the increased adhesion between microgels compromises the stretchability of the materials, thereby reducing their toughness.…”

Bioprinting of Cartilaginous Auricular Constructs Utilizing an Enzymatically Crosslinkable Bioink

“…Bioinks must provide a biologically favorable environment for cell proliferation and tissue maturation and support the generation of complex 3D constructs. [ 2 ] Novel strategies for combining these properties range from nanocomposite bioinks, [ 3 ] to interpenetrating network bioinks, [ 4 ] to microgel/microstrand printing [ 5 ] and combinations thereof [ 2b ] and have been applied to various types of biological tissues such as the musculoskeletal, [ 6 ] urinary [ 7 ] and cardiovascular [ 8 ] system.…”