Additive manufacturing (AM) using computer-assisted layer-bylayer material deposition is becoming an influential field in biological engineering and regenerative medicine. It holds the potential to regenerate or replace damaged tissue in order to help overcome organ failures and organ scarcity. In bio AM or biofabrication, biological material is deposited three dimensionally in a precise and efficient way. Custom-designed shapes, patterns, and architecture can be prepared, replicating biological tissue-level architecture. For biological engineering, a hydrogel is printed either with or without encapsulated cells. These hydrogels are a network of hydrophilic polymers, able to swell in water like the native tissue extracellular matrix (ECM), [1][2][3] and are the basic building blocks of defined 3D structures. Printed material composed of hydrogel with cells, is called bio-ink. But the cells do not necessarily have to be encapsulated before printing the construct. For a functional biofabricated 3D construct, cells can be seeded or grown into a previously printed design. [4] 3D bioprinting uses several technical solutions to print a defined pattern. Commonly used techniques are bioblotting (i.e., direct extrusion printing, direct dispensing), ink-jet printing, melt electro writing (MEW), solution electro writing (SEW), and electrospinning. Less commonly used or yet emerging techniques in bioprinting, are photo-curing 3D printing techniques like stereo lithography appearance (SLA), digital light processing (DLP), multijet printing (MJP),

Cell cultures aiming at tissue regeneration benefit from scaffolds with physiologically relevant elastic moduli to optimally trigger cell attachment, proliferation and promote differentiation, guidance and tissue maturation. Complex scaffolds designed with guiding cues can mimic the anisotropic nature of neural tissues, such as spinal cord or brain, and recall the ability of human neural progenitor cells to differentiate and align. This work introduces a cost-efficient gelatin-based submicron patterned hydrogel–fiber composite with tuned stiffness, able to support cell attachment, differentiation and alignment of neurons derived from human progenitor cells. The enzymatically crosslinked gelatin-based hydrogels were generated with stiffnesses from 8 to 80 kPa, onto which poly(ε-caprolactone) (PCL) alignment cues were electrospun such that the fibers had a preferential alignment. The fiber–hydrogel composites with a modulus of about 20 kPa showed the strongest cell attachment and highest cell proliferation, rendering them an ideal differentiation support. Differentiated neurons aligned and bundled their neurites along the aligned PCL filaments, which is unique to this cell type on a fiber–hydrogel composite. This novel scaffold relies on robust and inexpensive technology and is suitable for neural tissue engineering where directional neuron alignment is required, such as in the spinal cord.

Additive manufacturing (AM) using computer-assisted layer-bylayer material deposition is becoming an influential field in biological engineering and regenerative medicine. It holds the potential to regenerate or replace damaged tissue in order to help overcome organ failures and organ scarcity. In bio AM or biofabrication, biological material is deposited three dimensionally in a precise and efficient way. Custom-designed shapes, patterns, and architecture can be prepared, replicating biological tissue-level architecture. For biological engineering, a hydrogel is printed either with or without encapsulated cells. These hydrogels are a network of hydrophilic polymers, able to swell in water like the native tissue extracellular matrix (ECM), [1][2][3] and are the basic building blocks of defined 3D structures. Printed material composed of hydrogel with cells, is called bio-ink. But the cells do not necessarily have to be encapsulated before printing the construct. For a functional biofabricated 3D construct, cells can be seeded or grown into a previously printed design. [4] 3D bioprinting uses several technical solutions to print a defined pattern. Commonly used techniques are bioblotting (i.e., direct extrusion printing, direct dispensing), ink-jet printing, melt electro writing (MEW), solution electro writing (SEW), and electrospinning. Less commonly used or yet emerging techniques in bioprinting, are photo-curing 3D printing techniques like stereo lithography appearance (SLA), digital light processing (DLP), multijet printing (MJP),