Tissue-engineered collagenous fibrous cap models to systematically elucidate atherosclerotic plaque rupture.

A significant amount of vascular thrombotic events are associated with rupture of the fibrous cap that overlie atherosclerotic plaques. Cap rupture is however difficult to predict due to the heterogenous composition of the plaque, unknown material properties, and the stochastic nature of the event. Here, we aim to create tissue engineered human fibrous cap models with a variable but controllable collagen composition, suitable for mechanical testing, to scrutinize the reciprocal relationships between composition and mechanical properties. Myofibroblasts were cultured in 1 × 1.5 cm-sized fibrin-based constrained gels for 21 days according to established (dynamic) culture protocols (i.e. static, intermittent or continuous loading) to vary collagen composition (e.g. amount, type and organization). At day 7, a soft 2 mm ∅ fibrin inclusion was introduced in the centre of each tissue to mimic the soft lipid core, simulating the heterogeneity of a plaque. Results demonstrate reproducible collagenous tissues, that mimic the bulk mechanical properties of human caps and vary in collagen composition due to the presence of a successfully integrated soft inclusion and the culture protocol applied. The models can be deployed to assess tissue mechanics, evolution and failure of fibrous caps or complex heterogeneous tissues in general.

Immuno-regenerative biomaterials for in situ cardiovascular tissue engineering - Do patient characteristics warrant precision engineering?

In situ tissue engineering using bioresorbable material implants - or scaffolds - that harness the patient's immune response while guiding neotissue formation at the site of implantation is emerging as a novel therapy to regenerate human tissues. For the cardiovascular system, the use of such implants, like blood vessels and heart valves, is gradually entering the stage of clinical translation. This opens up the question if and to what extent patient characteristics influence tissue outcomes, necessitating the precision engineering of scaffolds to guide patient-specific neo-tissue formation. Because of the current scarcity of human in vivo data, herein we review and evaluate in vitro and preclinical investigations to predict the potential role of patient-specific parameters like sex, age, ethnicity, hemodynamics, and a multifactorial disease profile, with special emphasis on their contribution to the inflammation-driven processes of in situ tissue engineering. We conclude that patient-specific conditions have a strong impact on key aspects of in situ cardiovascular tissue engineering, including inflammation, hemodynamic conditions, scaffold resorption, and tissue remodeling capacity, suggesting that a tailored approach may be required to engineer immuno-regenerative biomaterials for safe and predictive clinical applicability.