Translational benchmarking of 3D in vitro models of traumatic brain injury.

Abstract

Traumatic brain injury (TBI) remains a major cause of neurological disability, yet effective therapies are limited. Advances in 3D in vitro neural models, including organoids, scaffold-based constructs, and brain-on-a-chip systems, have provided new opportunities to study neurotrauma under controlled conditions. This review evaluates recent in vitro tissue platforms through a dual framework of mechanical fidelity and biological response, benchmarking applied injury conditions against human biomechanical reconstructions and assessing the coverage of downstream responses relative to TBI pathology. Many 3D models apply clinically relevant mechanical loading regimes and reproduce select phenotypes, but remain limited by inconsistent mechanical reporting, incomplete cellular complexity, and sparse modeling of chronic and repetitive injury. Addressing these challenges will improve the translational utility of next-generation platforms.