Human tissue-engineered skeletal muscle: a novel 3D in vitro model for drug disposition and toxicity after intramuscular injection

摘要: The development of laboratory-grown tissues, referred to as organoids, bio-artificial tissue or tissue-engineered constructs, is clearly expanding. We describe for the first time how engineered human muscles can be applied a pre- non-clinical model intramuscular drug injection further decrease and complement use in vivo animal studies. muscle (BAM) formed seven day engineering procedure during which myoblasts fuse differentiate aligned myofibers an extracellular matrix. dimensions BAM constructs allow follow-up several days after injection. A stereotactic setup allows controllable at multiple sites BAM. injected compounds; dye, hydrolysable compound, reducible substrate wasp venom toxin. Afterwards, direct reflux, release metabolism were assessed comparison 2D cell culture isolated strips. Spectrophotometry luminescence allowed measure compounds their metabolites over time. profile 40 hours was observed contrast culture, showing capacity function depot. also determined compound toxicity on BAMs by measuring creatine kinase medium, increased with increasing toxic insult. Taken together, we show that injectable 3D used vitro.