Exploring the role of adventitial fibers in cerebral artery biomechanics for the subfailure damage regime.

Abstract

The gradual recruitment of tortuous medial collagen fibers underlies the nonlinear behavior of arteries within the physiological loading regime, while adventitial collagen fibers are hypothesized to act primarily as a protective element during supraphysiological loading events, such as balloon angioplasty. We examined five human cerebral artery specimens using multiphoton microscopy to image adventitial collagen during progressive supraphysiological uniaxial testing to failure. Fiber angles, tortuosity, and sublayer location were quantified for 3467 fibers across the adventitial thickness. A mixed-effects regression model assessed the effects of strain, tortuosity, sublayer index, and their interactions on circumferential fiber alignment. Higher strain significantly decreased fiber angles (p<0.001), indicating greater alignment, while higher tortuosity reduced alignment (p<0.01) and diminished aligning effects of strain (p<0.001). Sublayer position was also significant (p<0.001), with adventitial fibers closer to the media being more aligned. With increasing stretch, adventitial fibers first lose tortuosity. At higher stretch (λ^∗≈1.25±0.09, σ^∗≈0.92±0.27MPa), internal elastic lamina (IEL) tearing and adjacent medial fiber rupture occur, followed by circumferential adventitial fiber alignment. However, in this cohort (mean age 73.4±7.9 years), realignment was observed after multiple transverse IEL and medial tears had occurred. These findings provide quantitative, layer- and sublayer-specific evidence of a two-stage adventitial response, highlighting the coupled influence of loading, tortuosity, and wall depth on fiber alignment, and underscoring the need for high-fidelity models that explicitly incorporate layer-specific fiber architecture and failure mechanisms.