This peer-reviewed invited review recasts traumatic brain injury not as a single bruise to the head but as a system-wide disorder that ripples through the lungs, heart, kidneys, and gut. Synthesizing evidence from rodents, swine, and nonhuman primates through early human case reports, the authors examine mesenchymal stromal cell-derived extracellular vesicles, the tiny membrane-bound parcels cells shed to talk to one another. The synthesis reveals that these vesicles can quiet inflammation, blunt cell death, and coax new vessels and neurons. The authors map cargo engineering, delivery routes, and artificial intelligence-guided design while flagging the standardization gaps that still separate promise from practice.