We report the fabrication of a scaffold (hereafter referred to as AngioChip) that supports the assembly of parenchymal cells on a mechanically tunable matrix surrounding a perfusable, branched, three-dimensional microchannel network coated with endothelial cells. The design of AngioChip decouples the material choices for the engineered vessel network and for cell seeding in the parenchyma, enabling extensive remodelling while maintaining an open-vessel lumen. The incorporation of nanopores and micro-holes in the vessel walls enhances permeability, and permits intercellular crosstalk and extravasation of monocytes and endothelial cells on biomolecular stimulation. We also show that vascularized hepatic tissues and cardiac tissues engineered by using AngioChips process clinically relevant drugs delivered through the vasculature, and that millimeter-thick cardiac tissues can be engineered in a scalable manner. Moreover, we demonstrate that AngioChip cardiac tissues implanted via direct surgical anastomosis to the femoral vessels of rat hindlimbs establish immediate blood perfusion.
Significant advances in biomaterials, stem cell biology, and microscale technologies have enabled the fabrication of biologically relevant tissues and organs. Such tissues and organs, referred to as organ-on-a-chip (OOC) platforms, have emerged as a powerful tool in tissue analysis and disease modeling for biological and pharmacological applications. A variety of biomaterials are used in tissue fabrication providing multiple biological, structural, and mechanical cues in the regulation of cell behavior and tissue morphogenesis. Cells derived from humans enable the fabrication of personalized OOC platforms. Microscale technologies are specifically helpful in providing physiological microenvironments for tissues and organs. In this review, biomaterials, cells, and microscale technologies are described as essential components to construct OOC platforms. The latest developments in OOC platforms (e.g., liver, skeletal muscle, cardiac, cancer, lung, skin, bone, and brain) are then discussed as functional tools in simulating human physiology and metabolism. Future perspectives and major challenges in the development of OOC platforms toward accelerating clinical studies of drug discovery are finally highlighted.
Polyester
biomaterials are used in tissue engineering as scaffolds
for implantation of tissues developed in vitro. An ideal biodegradable
elastomer for cardiac tissue engineering exhibits a relatively low
Young’s modulus, with high elongation and tensile strength.
Here we describe a novel polyester biomaterial that exhibits improved
elastic properties for cardiac tissue engineering applications. We
synthesized poly(octamethylene maleate (anhydride) 1,2,4-butanetricarboxylate)
(124 polymer) prepolymer gel in a one-step polycondensation reaction.
The prepolymer was then molded as desired and exposed to ultraviolet
(UV) light to produce a cross-linked elastomer. 124 polymer exhibited
highly elastic properties under aqueous conditions that were tunable
according to the UV light exposure, monomer composition, and porosity
of the cured elastomer. Its elastomeric properties fell within the
range of adult heart myocardium, but they could also be optimized
for higher elasticity for weaker immature constructs. The polymer
showed relatively stable degradation characteristics, both hydrolytically
and in a cellular environment, suggesting maintenance of material
properties as a scaffold support for potential tissue implants. When
assessed for cell interaction, this polymer supported rat cardiac
cell attachment in vitro as well as comparable acute in vivo host
response when compared to poly(l-lactic acid) control. This
suggests the potential applicability of this material as an elastomer
for cardiac tissue engineered constructs.
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