Three-dimensional bioprinting to bridge the gap in spinal cord injuries

A novel 3D bioprinting technique allows for precise control over cell type positioning and axonal growth direction toward recapitulating the complex architecture of the spinal cord. Tissue engineering uses a combination of cells, signaling molecules, and biomaterial scaffolding to replace or regenerate damaged tissue. For spinal cord repair, most approaches have relied on direct injection of cells into the lesion without providing an adequate support system or recapitulating the native spinal cord structure. Recently, three-dimensional (3D) printing has emerged as a tool to create scaffolds that can mimic the structure of many tissues. Nonetheless, it remains a challenge to use 3D printing to replicate heterogeneous tissues with multiple cell types and complex architecture, such as the central nervous system. To address this challenge, Joung and colleagues developed a novel 3D neuro-bioprinting technique capable of precisely controlling the positioning of multiple cell types. Two types of cells, spinal neuronal progenitor cells (sNPCs) and oligodendrocyte progenitor cells (OPCs), were printed directly onto silicone scaffolds with 150 μm-diameter channels. The authors demonstrated the ability to print the cells separately or in combination with precise control over cell type spatial positioning using a point-dispensing method while maintaining good cell viability. After one week, sNPCs differentiated into neurons with axons extending along the silicone channels. Calcium imaging was used to evaluate neuronal activity; the authors showed that cells responded to high potassium and glutamate, indicating differentiation into functionally mature neurons. Similar results were also obtained using a biocompatible printing material as the scaffold'alginate blended with methylcellulose'allowing for simultaneous printing of the cells and scaffold. Eventually the authors hope to use their novel 3D neuro-bioprinting technique to both guide axonal growth of differentiated neurons and allow for myelination of these axons via oligodendrocytes differentiated from 3D-printed OPCs. 3D printing is a promising tool for manufacturing “living” materials that recapitulate the complex multicellular architecture of biological tissues. Here, the authors detail a novel bioprinting method capable of precisely controlling cell positioning and axonal growth direction. Although all the current work was performed in vitro, recapitulating the heterogeneous nature of the spinal cord is likely critical for functional regeneration of the spinal cord in vivo. Additionally, the multicellular bioprinting approach detailed in this manuscript is broadly applicable to a wide range of multicellular tissues with complex architectures.