P3 Development of a functional, human model of medial arterial calcification

Introduction Medial arterial calcification is mediated by phenotypical changes of vascular smooth muscle cells (VSMCs) to osteoblastic and osteocytic type cells. It is associated with continuously high calcium phosphate levels within the body, a common occurrence in diabetes and chronic kidney disease. As the pathogenesis of medial calcification is not understood yet, and there is currently no treatment or early detection methods, the development of an advanced human model is crucial for further research progression.

Aims In this study a cell-seeded electrospun gelatine membrane mimics the mechanics, morphology and pathology of a calcified human artery, providing a more flexible and physiologically relevant cell environment compared to common, rigid tissue plastic. Tuning fibre alignment in the electrospun membrane prompts SMC alignment, resembling natural arterial morphology. Cell orientation is essential when replicating native smooth muscle tissue, as it strongly influences SMC phenotype, functionality and cell-cell interactions.

Methods Calcification in human umbilical artery smooth muscle cells (HUASMC) is induced by high calcium phosphate levels. Changes in phenotype and gene expression are characterised using immunostaining and advanced imaging techniques.

Results Aligned SMC show a higher degree of calcification when compared with unaligned SMCs when growing on the membrane. Common tissue culture plastic leads to significantly lower calcification in comparison.

Future Work This work describes progress towards a bioengineered human arterial calcification model, which can be easily adapted to study other vascular diseases. It will be further developed into a microfluidic Organ-on-a-chip model of human artery disease, allowing additional control over vascular hemodynamics including hypertension and vascular narrowing, as well as the integration of biosensors for real time monitoring.