The ideal engineered vascular graft would utilize human-derived materials to minimize foreign body response and tissue rejection. Current biological engineered blood vessels (BEBVs) inherently lack the structure required for implantation. We hypothesized that an ECM material would provide the structure needed. Skin dermis ECM is commonly used in reconstructive surgeries, is commercially available and FDA-approved. We evaluated the commercially-available decellularized skin dermis ECM Alloderm for efficacy in providing structure to BEBVs. Alloderm was incorporated into our lab’s unique protocol for generating BEBVs, using fibroblasts to establish the adventitia. To assess structure, tissue mechanics were analyzed. Standard BEBVs without Alloderm exhibited a tensile strength of 67.9 ± 9.78 kPa, whereas Alloderm integrated BEBVs showed a significant increase in strength to 1500 ± 334 kPa. In comparison, native vessel strength is 1430 ± 604 kPa. Burst pressure reached 51.3 ± 2.19 mmHg.
Fig: Diagram of self-assembled rings with incorporated Alloderm. Alloderm was integrated into the engineered vascular rings by placing the ECM material into the plate prior to cell seeding. Fibroblasts were seeded on top of the Alloderm and hydrogel, and the cells were able to infiltrate both the Alloderm ECM and hydrogel. Plate images show the progression of the engineered vascular ring formation 1 day and 14 days following seeding, showing the cell monolayer with hydrogel (edge indicated by white arrows) and the location of the Alloderm (black arrow) in the final ring tissue. Scale bar = 1 cm.
Total collagen and fiber maturity were significantly increased due to the presence of the Alloderm material. Vessels cultured for 4 weeks maintained mechanical and structural integrity. Low probability of thrombogenicity was confirmed with a negative platelet adhesion test. Vessels were able to be endothelialized. These results demonstrate the success of Alloderm to provide structure to BEBVs in an effective way.
Patel, B., Wonski, B.T., Saliganan, D.M. et al. Decellularized dermis extracellular matrix alloderm mechanically strengthens biological engineered tunica adventitia-based blood vessels. Sci Rep 11, 11384 (2021). https://doi.org/10.1038/s41598-021-91005-9