Biofabrication and mechanical characterization of hydrogel-based atherosclerotic plaques for the in vitro testing of drug-coated balloons

Realistic in vitro models are essential to the evalation and development of new treatments. In this work, a hydrogel-based atherosclerotic plaque was fabricated and mechanically characterized with the purpose to be used in drug-coated balloon (DCB) performance testing. Gelatin-based hydrogels were preliminary evaluated, glutaraldehyde and genipin were tested as crosslinkers, the latter being chosen as the definite crosslinker. The goal was to mimic fibrous (type VIII) and calcified (type VII) atherosclerotic plaques, hydroxyapatite (HA) was added to mimic the latter. Unconfined compression test were conducted on the hydrogels where the maximum stress reached at 25% strain and the tangential stiffness at 20% strain were considered to be successfully replicated. Unfortunately, when performing three consecutive stress relaxation tests, the hydrogels did not reproduce the mechanical behavior over time of the real plaques. The hydrogels were made of biocompatible components, had a gelation time of 5 to 6 minutes, and swelling and stability tests indicated stability and no major changes in volume for at least 8 days when immersed in PBS. Wettability tests were performed, and based on Young’s equation it was determined that hydrogel’s surfaces were slightly hydrophobic or slightly hydrophilic. Although the mechanical behavior over time was not replicated, this work appears to have the potential to be an adequate option towards a realistic in vitro model that contains an artificial atherosclerotic plaque to evaluate the effectiveness of DCB on SFA.