A multi-scale mechanobiological framework for vibration-induced intimal hyperplasia.

Intimal hyperplasia is a pathological mechanism underlying arterial growth and remodeling in numerous vascular diseases, in which key biological processes are regulated by mechanical fields such as wall shear stress (WSS) and circumferential stress within the artery walls. In the present study, we hypothesize that chronic exposure to hand-arm vibrations (HAV) contributes to the development of intimal hyperplasia in the digital artery through vibration-induced reductions in WSS. Accordingly, a mechanobiological framework coupling an agent-based model (ABM) with a finite element model (FEM) was developed. The ABM captures the hemodynamics-driven and mechanoregulated cellular and molecular mechanisms involved in this pathology, including mediator secretion by endothelial and smooth muscle cells (SMCs), SMCs proliferation and migration, and extracellular matrix (ECM) synthesis and degradation. WSS values, reflecting the presence or absence of vibration during long-term working conditions, were used as model inputs. Circumferential stresses were computed using the FEM, which describes the mechanical behavior of the digital artery. The model parameters were identified from our experimental findings and literature data. Over a 5 year period of vibration exposure (4 h/day), our simulations revealed that the constitutive law of the arterial walls had a negligible impact on the progression of stenosis. Moreover, reductions in circumferential stress associated with arterial wall thickening led to ECM degradation in the media layer due to an increase in the production of matrix metalloproteinase-2. This mechanobiological framework provides a computational tool for estimating vibration-induced stenosis rates and can be extended to study intimal hyperplasia in diverse biomechanical and pathological contexts.