Vascular tissue engineering, creation of small-diameter vascular grafts

Even in modern medicine, full-fledged and functional vascular grafts remain an unsolved problem.  More than 70 years after the first vascular graft was introduced into clinical practice, only acellular grafts are routinely used, whether they are synthetic polymers or biological matrices (allogeneic or xenogeneic). Small-diameter (less than 6 mm) artificial grafts almost always undergo stenosis and obliteration, resulting in failure. This is because they lack a continuous inner lining of endothelial cells, the most effective prevention against thrombosis and other pathological changes. There is a possibility of spontaneous endothelialization of vascular grafts through capillaries growing into the graft from surrounding tissues (doi: 10.3389/fcvm.2020.00159). However, this possibility of spontaneous endothelialization is limited in human patients. Therefore, we will facilitate this process during the in vitro construction of the vascular graft.

A porous substrate, ideally made of biopolymers (cellulose, particularly bacterial nanocellulose) or degradable synthetic polymers (polycaprolactone), will be seeded with mesenchymal stem cells (MSCs; e.g., from subcutaneous adipose tissue) and covered with hydrogel (e.g., collagen) mixed with endothelial cells. As we have verified in preliminary experiments, MSCs will colonize the hydrogel and support the formation of capillary-like tubular structures by endothelial cells. Once these pre-capillaries reach the surface of the hydrogel, they emerge on it, and the endothelial cells form a continuous layer, which becomes the basis of the tunica intima of the vascular wall. The MSCs colonizing the hydrogel will then be differentiated towards smooth muscle cells, mimicking the tunica media. We will determine the optimal ratio between endothelial and stem cells, the appropriate ratio of vasculogenic and differentiation media, and the optimal timing of intima and media reconstruction to ensure that the vascularization of the construct does not interfere with cell differentiation (doi: 10.1089/ten.tea.2020.0330). In its planar form, our tissue construct can serve as a vascular patch, and in its tubular form, as a small-diameter blood vessel replacement.

We are looking for collaboators-material engineers, who can provide us with a biocompatible, mechanically strong scaffolds, and also biologists, who can help us to solve the "conflict" between the pre-vascularization and smooth muscle cell differentiation. We are also looking for clinical collaborators and companies to help us implement our newly developed constructs.

https://fgu.cas.cz/en/research-and-laboratories/research-departments/laboratory-of-biomaterials-and-tissue-engineering/