Additive manufacturing in spatial patterning for spinal cord injury treatment

Combinatorial treatments integrating cells and biomolecules within scaffolds have been investigated to address the multifactorial nature of spinal cord injury (SCI). Current regenerative treatments have been ineffective as they do not consider the spatial positions of various cell types to effectively form functional neural pathways. Emulating the complex heterogeneity of cells in the native spinal cord requires translating the existing biological understanding of spatial patterning in neural development, as well as the influence of biomolecule and mechanical patterning on regional specification and axonal regeneration, to engineer a scaffold for spinal cord regeneration. This review explores the potential of 3D bioprinting to precisely control material, cell and drug patterns in scaffolds, achieving spatial phenotype specification and providing axonal guidance to form appropriate connections. We also discuss the application of extrusion-based and digital light processing bioprinting in integrating mechanical, chemical and biological cues within a scaffold to advance spatially patterned 3D bioprinted scaffold, as well as current challenges and future perspectives in these bioengineering strategies.