During development, cell fate and organ growth are dictated via a combination of cell-cell and extracellular matrix (ECM)-cell interactions and signals. We focus on how cells communicate with their surrounding ECM and their associated growth factors, and how we can harness these interactions to improve regeneration and develop therapies that have the potential to reduce scar formation and improve regeneration. Among the ECM components, the glycoprotein laminin can form a protein network that provides structural scaffolding for tissues and organs, and has an important role in skeletal muscle regeneration. Defective laminin within skeletal muscle can lead to a debilitating disease known as merosin-deficient congenital muscular dystrophy type 1A (MDC1A). Thus, exogenous laminin protein therapy is an option to improve dystrophic muscle and to enhance muscle regeneration. We also discuss zebrafish spinal cord regeneration, and as with muscle regeneration, environmental cues surrounding cells are critical for a regenerative capacity. By comparing zebrafish spinal cord regeneration with mammals, we can identify specific growth factors that help provide a pro-regenerative environment.