Angiogenesis and Vascularization Model from Allevi Authors

In their recent publication, Allevi authors Serkan Dikici, Fredrick Claeyssens, and Sheila MacNeil developed a very clever synthetic vascular network (SVN) by combining electro-spun layers with 3D bioprinted vascular channels. This unique construct demonstrated angiogenesis (the process through which new blood vessels form from pre-existing vessels) and vascularization.

Creating the Construct

The researchers used sodium alginate as a sacrificial bioink which they printed with their Allevi 2. This channel design was sandwiched between two layers of electro-spun Poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV). They then dissolved the sodium alginate, creating a construct ready for cell seeding in their subsequent experiments. The construct helped create clinically relevant engineered skin tissue incorporating blood vessels. Their PHBV layers provided an excellent texture for supporting dermal cells. Meanwhile, their 3D printed channel provided an excellent environment for endothelial cells as well as a route for perfusion. The researchers were able to make multiple constructs at a time with a high degree of reproducibility and customizability.

Key Findings

The two key results were the demonstration of both angiogenesis into Matrigel® pockets and vascularization in a chick chorioallantoic membrane (CAM) assay. To demonstrate angiogenesis, the researchers introduced Matrigel® loaded with growth factors near the channels of the construct. Over time, they were able to image tubes of Human Dermal Microvascular Endothelial Cells (HDMECs) growing into the gel. Further, these tubes were branching, showing the expected growth behavior for proper angiogenesis.

To demonstrate vascularization, the researchers cultured an engineered skin tissue patch in the construct. After maturation, they performed a CAM assay in which the tissue patches were incorporated in chick embryos. They saw relatively healthy incorporation on several of the patches indicating good vascularization in the tissue.

While previous work has shown angiogenesis and vascularization, especially with skin tissue, this model notably shows both simultaneously. The combination lends a further degree of clinical relevance to the model. It also provides progress on the current problem of vascularizing complex tissue in tissue engineering.

You can check out their paper, Bioengineering Vascular Networks to Study Angiogenesis and Vascularization of Physiologically Relevant Tissue Models in Vitro, in ACS Biomaterials, Science & Engineering. You can also read about other inspirational Allevi Authors on the Allevi Blog!