The development of techniques for fabricating vascular wall models will foster the development of preventive
and therapeutic therapies for treating cardiovascular diseases. However, the physical and biological
complexity of vascular tissue represents a major challenge, especially for the design and the production
of off-the-shelf biomimetic vascular replicas. Herein, we report the development of a biocasting
technique that can be used to replicate the tunica adventitia and the external elastic lamina of the vascular
wall. Type I collagen embedded with neonatal human dermal fibroblast (HDFn) and an elastic click crosslinkable,
cell-adhesive and protease-sensitive elastin-like recombinamer (ELR) hydrogel were investigated
as readily accessible and tunable layers to the envisaged model. Mechanical characterization confirmed
that the viscous and elastic attributes predominated in the collagen and ELR layers, respectively. In vitro
maturation confirmed that the collagen and ELR provided a favorable environment for the HDFn viability,
while histology revealed the wavy and homogenous morphology of the ELR and collagen layer respectively,
the cell polarization towards the cell-attachment sites encoded on the ELR, and the enhanced
expression of glycosaminoglycan-rich extracellular matrix and differentiation of the embedded HDFn into
myofibroblasts. As a complementary assay, 30% by weight of the collagen layer was substituted with the
ELR. This model proved the possibility to tune the composition and confirm the versatile character of the
technology developed, while revealing no significant differences with respect to the original construct.
On-demand modification of the model dimensions, number and composition of the layers, as well as the
type and density of the seeded cells, can be further envisioned, thus suggesting that this bi-layered model
may be a promising platform for the fabrication of biomimetic vascular wall models.
