3D bioprinting complex models of cancer.

Cancer is characterized by the uncontrolled division of cells, resulting in the formation of tumors. The tumor microenvironment (TME) consists of a variety of cell types present within a heterogeneous extracellular matrix (ECM). Current 2D culture methods for mimicking this microenvironment remain limited due to spatial constraints. Many different types of 3D cancer models have been developed in recent years using spheroids/organoids, biomaterial scaffolds, and cancer-on-chip systems. However, these models cannot precisely control the organization of multiple cell types inside of complex architectures. Bioprinted cancer models can incorporate both stromal and cancer cells inside of 3D constructs to generate custom models of this complex disease. 3D bioprinting can generate complex, multicellular, and reproducible constructs where the matrix composition and rigidity are tailored locally to the tumor. These capabilities make 3D bioprinting an attractive method for reproducing the tumor TME found in vivo. Recent advancements in biomaterial-based bioinks enable the generation of 3D bioprinted cancer models that accurately mimic the TM. Here we discuss recent examples of such 3D-bioprinted cancer models, including those of the lungs, prostate, skin, brain, and colon. We then highlight the advantages of using 3D bioprinting compared to other in vitro modeling techniques and detail its limitations.

CRISPR, Prime Editing, Optogenetics, and DREADDs: New Therapeutic Approaches Provided by Emerging Technologies in the Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) causes temporary disabilities or permanent effects including neuropathic pain and spastiscity. The damage often results from mechanical trauma, which in turn triggers the neuroinflammatory process. Neuroinflammation plays essential roles in the structural, biochemical, and cellular changes that take place in the spinal cord after the injury. Indeed, SCI activates many different signaling pathways that coordinate the resulting cellular responses. While neuroinflammation serves as a physiological reaction to harmful stimuli, it is clear that long-lasting inflammatory response leads to aggravation of the neurodegenerative processes, becoming detrimental to recovery post-injury. In this context, we present some possible therapeutic targets in these activated signaling pathways and provide new perspectives for SCI treatment based on recently developed technologies, including clustered regularly interspaced short palindromic repeats (CRISPR)-based methods (including prime editing), optogenetics, and designer receptor exclusively activated by designer drugs (DREADDs). We critically analyze the recent advances in the deployment of these methods focusing on the control of the initial neuroinflammatory response. We then propose alternatives and provide new avenues for SCI treatment based on these emerging technologies.