# Advancing in vitro vascular wall modelling using digital light processing to study hyperglycemia-driven cell changes

## TL;DR

This study develops a 3D vascular wall model using 3D-printed scaffolds to study how high glucose levels affect blood vessel cells in metabolic syndrome.

## Contribution

The study introduces a novel in vitro vascular wall model using DLP-printed scaffolds and GelMA coatings to study hyperglycemia effects on cells.

## Key findings

- GelMA-coated scaffolds improved the cytocompatibility and allowed MSC trilineage differentiation.
- High glucose conditions significantly reduced the viability of endothelial cells but not mesenchymal stromal cells.
- The model mimics endothelial damage seen in metabolic syndrome and replicates 2D culture effects in 3D.

## Abstract

Metabolic syndrome is a pathological state, frequently associated with type 2 diabetes, which is marked by abdominal obesity, impaired insulin action, hypertension, and vascular wall changes. Similar to humans, horses can suffer from equine metabolic syndrome. A representative in vitro vascular wall model is needed to study its pathophysiology and develop novel treatments for both human and equine patients.

In this study, scaffolds manufactured via digital light processing (DLP) exploiting an acrylate-endcapped urethane-based polymer precursor with a polyethylene glycol backbone (AUP2PEG) were coated with collagen or gelatin derivatives. Their cell-interactive properties were evaluated using equine mesenchymal stromal cells (MSC) and endothelial cells (EC). Coating was performed using either UV-induced photopolymerization of gelatin methacryloyl (GelMA) on the surface of the DLP-printed scaffold or physisorption of type I atelocollagen.

The GelMA coating formed a thin, uniform layer on the scaffold surface and improved the cytocompatibility of DLP-printed AUP2PEG-based scaffolds for EC and MSC. Furthermore, they permitted MSC trilineage differentiation. To mimic the endothelial damage occurring in metabolic syndrome conditions, the GelMA-coated AUP2PEG scaffolds were incubated in high glucose culture conditions. Short-term cell culture in these conditions significantly reduced the number of viable EC. In contrast, the short-term culture of MSC in these conditions did not result in a similarly deleterious impact on cell viability.

In conclusion, GelMA-coated DLP-printed AUP2PEG scaffolds facilitate the growth of EC and MSC. Furthermore, exposing EC cultured on the developed scaffolds to hyperglycemic culture conditions negatively affects the viability of EC, comparable to what is observed in two-dimensional culture conditions.