Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis

Abstract

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.

Generation, Endothelialization, and Microsurgical Suture Anastomosis of Strong 1-mm-Diameter Collagen Tubes

“…On the other hand, dried-and-crosslinked collagen tubes yielded average burst pressures of *1300 mm Hg, which is comparable to the value obtained by Chaikof and coworkers for tubes of 1.3 mm inner diameter. 18 While this value is still shy of the burst pressure of native arteries (which can be as high as 3000 mm Hg) 25 , it is close to the value for native vein (*1200 mm Hg) 26 and more than sufficient to withstand pressure of arterial flow. Compliance of dried-andcrosslinked tubes averaged *1.7%/100 mm Hg, which is comparable to the value (0.7-2.6%/100 mm Hg) of mammalian vein.…”

“…To the best of our knowledge, nearly all other studies that claim anastomosis between an engineered collagen-based scaffold and native vessels £1 mm outer diameter used a polymer mesh to reinforce the anastomosis, 29 or surgical glue in place of suture. 26 Only a few groups have engineered implantable vascular grafts at the £1 mm scale. Narita and coworkers reported making grafts of 0.7 mm inner diameter from poly-ecaprolactone.…”

Modular assembly of thick multifunctional cardiac patches

“…For example, because cardiac cells and blood vessel cells require different culture medium and distinct ECM structure and composition, and mature at different time points, engineering spatially controlled vasculature within a cardiac patch may be a challenge (17,18). To overcome these challenges, recent advances in lithographic methods have enabled the layer-bylayer assembly of anisotropic 3D cardiac tissues and a vascular compartment embedded within them (19)(20)(21). For example, Zhang and colleagues (21) have reported on the production of a biodegradable scaffold with a built-in vasculature.…”

“…To overcome these challenges, recent advances in lithographic methods have enabled the layer-bylayer assembly of anisotropic 3D cardiac tissues and a vascular compartment embedded within them (19)(20)(21). For example, Zhang and colleagues (21) have reported on the production of a biodegradable scaffold with a built-in vasculature. In a different study Ye and colleagues (20) reported the stacking of elastomeric microvessels and heart cell scaffolds to form 3D vascularized tissues.…”

Human pluripotent stem cell-derived cardiomyocyte based models for cardiotoxicity and drug discovery

“…Also, by integrating vasculature models into the ECTs, such as the recent AngioChip (Figure 1(j-m)) [20], a circulatory system could be generated to investigate drug delivery methods as well as the effect of the endothelium. Finally, since most drug delivery methods can result in a systemic exposure to either the drug or its by-products, micro tissues corresponding to the clearance organs, the liver and kidney, upstream of the ECT compartment could provide valuable information about the interaction of the drug with these organs and the downstream consequences.…”