Cancer Models on Chip: Paving the Way to Large-Scale Trial Applications.

Cancer kills millions of individuals every year all over the world (Global Cancer Observatory). The physiological and biomechanical processes underlying the tumor are still poorly understood, hindering researchers from creating new, effective therapies. Inconsistent results of preclinical research, in vivo testing, and clinical trials decrease drug approval rates. 3D tumor-on-a-chip (ToC) models integrate biomaterials, tissue engineering, fabrication of microarchitectures, and sensory and actuation systems in a single device, enabling reliable studies in fundamental oncology and pharmacology. This review includes a critical discussion about their ability to reproduce the tumor microenvironment (TME), the advantages and drawbacks of existing tumor models and architectures, major components and fabrication techniques. The focus is on current materials and micro/nanofabrication techniques used to manufacture reliable and reproducible microfluidic ToC models for large-scale trial applications.

Chondrogenic differentiation of mesenchymal stem/stromal cells on 3D porous poly (ε-caprolactone) scaffolds: Effects of material alkaline treatment and chondroitin sulfate supplementation.

Cartilage defects resultant from trauma or degenerative diseases (e.g., osteoarthritis) can potentially be repaired using tissue engineering (TE) strategies combining progenitor cells, biomaterial scaffolds and bio-physical/chemical cues. This work examines promoting chondrogenic differentiation of human bone marrow mesenchymal stem/stromal cells (BM-MSCs) by combining the effects of modified poly (ε-caprolactone) (PCL) scaffolds hydrophilicity and chondroitin sulfate (CS) supplementation in a hypoxic 5% oxygen atmosphere. 3D-extruded PCL scaffolds, characterized by µCT, featured a 21 mm-1 surface area to volume ratio, 390 µm pore size and approximately 100% pore interconnectivity. Scaffold immersion in sodium hydroxide solutions for different periods of time had major effects in scaffold surface morphology, wettability and mechanical properties, but without improvements on cell adhesion. In-situ chondrogenic differentiation of BM-MSC seeded in 3D-extruded PCL scaffolds resulted in higher cell populations and ECM deposition along all scaffold structure, when chondrogenesis was preceded by an expansion phase. Additionally, CS supplementation during BM-MSC expansion was crucial to enhance aggrecan gene expression, known as a hallmark of chondrogenesis. Overall, this study presents an approach to tailor the wettability and mechanical properties of PCL scaffolds and supports the use of CS-supplementation as a biochemical cue in integrated TE strategies for cartilage regeneration.