Coaxial nanofiber design for traumatic brain injury: a review and framework for phase-responsive therapeutics

Traumatic brain injury (TBI) is characterized by an evolving pathophysiology spanning acute, subacute, and chronic stages, each demanding temporally tailored therapeutic interventions. However, conventional drug delivery systems lack the capacity to adapt to these shifting biological windows, limiting therapeutic precision and clinical efficacy. Coaxial electrospun nanofibers, with their spatially distinct core-shell architecture, offer a platform for phase-responsive drug delivery, enabling temporal modulation of therapeutic release. In this review and design framework, we explore how the structural logic of coaxial nanofibers can be leveraged to address the temporally distinct therapeutic needs of TBI. We align polymer composition, fiber geometry, and degradation kinetics with the molecular and cellular hallmarks of each injury phase, emphasizing design strategies that synchronize scaffold behavior with evolving oxidative, neuroinflammatory, and regenerative processes. The review also outlines a roadmap for programmable coaxial electrospun nanofiber design logic for TBI application. By structurally aligning therapeutic delivery with TBI's temporal dynamics, phase-responsive nanofiber scaffolds may advance the field toward more precise, adaptive, and effective neurotherapeutics.