Nanoengineered Granular Hydrogel Bioinks with Preserved Interconnected Microporosity for Extrusion Bioprinting

Abstract

3D bioprinting of granular hydrogels comprising discrete hydrogel microparticles (microgels) may overcome the intrinsic structural limitations of bulk (nanoporous) hydrogel bioinks, enabling the fabrication of modular thick tissue constructs. The additive manufacturing of granular scaffolds has predominantly relied on highly jammed microgels to render the particulate suspensions shear yielding and extrudable. This inevitably compromises void spaces between microgels (microporosity), defeating rapid cell penetration, facile metabolite and oxygen transfer, and cell viability. Here, this persistent bottleneck is overcome by programming microgels with reversible interfacial nanoparticle self‐assembly, enabling the fabrication of nanoengineered granular bioinks (NGB) with well‐preserved microporosity, enhanced printability, and shape fidelity. The microporous architecture of bioprinted NGB constructs permits immediate post‐printing 3D cell seeding, which may expand the library of bioinks via circumventing the necessity of bioorthogonality for cell‐laden scaffold formation. This work opens new opportunities for the 3D bioprinting of tissue engineering microporous scaffolds beyond the traditional biofabrication window.

Iron Inhibits Glioblastoma Cell Migration and Polarization

“…To this end, T98G and LN229 cells were labeled with a fluorescent dye, followed by 3D topical seeding on granular hydrogel scaffolds ( Figure 2A) . Granular hydrogel scaffolds provide interconnected microporosity, enabling oxygen, nutrient, and cellular waste transport [16,24]. The microporosity enables nutrient gradient generation, facilitating cell migration within the scaffold [25].…”

“…3D granular hydrogel scaffolds were synthesized from gelatin methacryloyl (GelMA) hydrogel microparticles as previously described [16][17][18]. Further details regarding the hydrogel scaffold synthesis are available in the Supplementary Information.…”

The Role of Microsphere Structures in Bottom-Up Bone Tissue Engineering

“…Therefore, there is currently an unmet need to develop granular jammed hydrogels that can preserve the microscale pores [ 212 ]. Ataie and co-workers programmed microgels for reversible interfacial nanoparticle self-assembly, enabling the fabrication of nanoengineered granular bioinks with well-preserved microporosity, enhanced printability, and shape fidelity [ 213 ]. Four-dimensional printing is a rapidly emerging field that has been developed from 3D printing, where printed structures change in shape, properties, or function when exposed to predetermined stimuli, such as humidity and temperature photoelectric stimuli.…”

3D Printing of Self‐Assembling Nanofibrous Multidomain Peptide Hydrogels

“…Although multiple 3D printing methods exist, extrusion‐based printing has been most widely adopted due to its simplistic working principle and ease of use. [ 3,4 ] Inks used in extrusion 3D printing mainly consist of chemically modified versions of gelatin, [ 5–12 ] alginate, [ 13–16 ] hyaluronic acid, [ 17–20 ] collagen, [ 1,21,22 ] decellularized extracellular matrix, [ 23–25 ] or combinations of these. [ 26–35 ] The traditional approach for developing 3D printable inks has been to chemically modify naturally‐derived hydrogel materials to make them more printable, while attempting to maintain their favorable biological properties.…”

“…Although multiple 3D printing methods exist, extrusion-based printing has been most widely adopted due to its simplistic working principle and ease of use. [3,4] Inks used in extrusion 3D printing mainly consist of chemically modified versions of gelatin, [5][6][7][8][9][10][11][12] alginate, [13][14][15][16] hyaluronic acid, [17][18][19][20] collagen, [1,21,22] decellularized extracellular matrix, [23][24][25] or combinations of these. [26][27][28][29][30][31][32][33][34][35] The traditional approach for developing 3D printable inks invented a fabrication method that included extrusion printing followed by spraying a salt gelling agent at each layer.…”