Advanced Solutions Discovers a Way to Guide New Blood Vessel Growth Across Tissue Boundaries

Advanced Solutions’ Angiomics™ microvessels enable vascularized tissue models, spheroids, and 3D culture

One of the biggest challenges facing the field of tissue engineering is building a stable yet adaptable microcirculation outside of the body. Advanced Solutions is pioneering the use of human-derived, isolated microvessel fragments in building vasculatures in ex-vivo tissues and tissue models.

A recent article published in Frontiers in Physiology, conducted in partnership with the University of Utah’s Scientific Computing and Imaging Institute, demonstrated how stromal cells and chemical cues can be deployed in 3D models to help guide new vessel growth between tissue boundaries and compartments.

Angiogenesis - the development of new blood vessels – involves the formation of new vasculatures during development, tissue healing, tumor formation, and tissue grafting. A largely under-studied aspect of angiogenesis is the process by which growing vessels navigate through complex tissue structures and stromal compartments in adult humans.

Figure 1: The Core-in-field (CIF) tissue boundary model. (A) Schematic of the CIF model showing the preformed “core” sitting on a thin bed of gelled collagen surrounded by an additional “field” of gelled collagen.

To further explore this important vascular biology, the Advanced Solutions’ team created a novel in-vitro 3D model of a tissue interface consisting of a high-density collagen layer formed between two lower density collagen compartments. In this experiment, the team combined this 3D tissue model system with Angiomics™ microvessels to evaluate how neovessels growing from the parent microvessel fragments across tissue boundaries as they form an expanded neovascular network.

The team observed that, unexpectedly, angiogenic neovessels are unable to spontaneously cross the dense collagen interface. The evidence suggested that this was due to the condensed nature of the fibril network of the 3D collagen at the interface, which impeded the neovessel growth across the interface. Years of work by the collaborative team has shown that collagen fibril density, as well as the alignment of the fibrils, provide guidance cues for growing neovessels resulting in differences in neovessel growth rates, branching, and direction.

Informed by in vivo implant studies involving the microvessels, further experimentation revealed that stromal cells promoted neovessel invasion through the interface into the neighboring collagen compartment and that this involved biochemical cues from the stromal cells. Additional findings suggest that spatiotemporal cues, perhaps as angiogenic factors, generated by the stromal cells overrode the mechanical cues of the deflective interface to promote neovessel growth into neighboring tissue compartments. In the absence of stromal cells, these factor gradients could be designed into the 3D matrix architecture (3D bioprinting for porosity, fibril layout, solute diffusion) and/or ligand distribution.

Better understanding the rules of angiogenesis is helping the Advanced Solutions’ team become the market leader in biofabrication of vascularized, biologically relevant tissue models on their mission to deliver curative solutions.

Learn how to use Angiomics™ microvessels to vascularize your 3D Cell Culture.

Questions? Get in touch with our Vascularization team

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