elastin and procyanidin

Elastin, a main component of decellularized extracellular matrices and elastin-containing materials, has been used for tissue engineering applications due to their excellent biocompatibility. However, elastin is easily calcified, leading to the decrease of life span for elastin-based substitutes. How to inhibit the calcification of elastin-based scaffolds, but maintain their good biocompatibility, still remains significantly challenging. Procyanidins (PC) are a type of natural polyphenols with crosslinking ability. To investigate whether pure elastin could be crosslinked by PC with anti-calcification effect, PC was first used to crosslink aortic elastin. Results show that PC can crosslink elastin and effectively inhibit elastin-initiated calcification. Further experiments reveal the possible mechanisms for the anti-calcification of PC crosslinking including (1) inhibiting inflammation cell attachment, and secretion of inflammatory factors such as MMPs and TNF-α, (2) preventing elastin degradation by elastase, and (3) direct inhibition of mineral nucleation in elastin. Moreover, the PC-crosslinked aortic elastin maintains natural structure with high pore volume (1111 μL/g), large pore size (10-300 μm) and high porosity (75.1%) which facilitates recellularization of scaffolds in vivo, and displays excellent hemocompatibility, anti-thrombus and anti-inflammatory potential. The advantages of PC-crosslinked porous aortic elastin suggested that it can serve as a promising scaffold for tissue engineering.

Topics: Animals; Aorta; Biflavonoids; Blood Coagulation; Calcification, Physiologic; Catechin; Cell Adhesion; Cell Line; Cross-Linking Reagents; Elastin; Glutaral; Heart Valves; Hemolysis; Humans; Macrophages; Matrix Metalloproteinase 12; Minerals; Pancreatic Elastase; Platelet Adhesiveness; Porosity; Proanthocyanidins; Proteolysis; Rats, Sprague-Dawley; Staining and Labeling; Sus scrofa; Tissue Scaffolds

Tissues are composed of cells and extracellular matrix (EM). Adhesion of cells to extracellular matrix is mediated by membrane-bound glycoproteins such as fibronectin, laminin and others. Elastonectin was shown recently to be involved in the mediation of interactions between elastic fibers and cells such as human skin fibroblasts (FB) and smooth muscle cells (SMC) from the media of the aorta. A strong interaction between fibers and cells is important for the maintenance of the quality of the vascular wall. We studied the action of procyanidolic oligomers (PCO) on the attachment of fibroblasts from human skin and smooth muscle cells from porcin aorta to elastic fibers. A dose-dependent increase of cell-fiber interaction could be demonstrated with both cell-types. Elastonectin is located on the cell membrane as well as an elastolytic serine-protease exhibiting an age- and pathology-dependent increase in activity. This will result in a degradation of elastic lamellae, the detachment of cells from elastic fibers and a weakening of the vascular wall. The activity of procyanidolic oligomers increasing the resistance of elastic fibers to degradation by elastases and enhancing the interaction between fibers and cells can be considered as favouring the maintenance of the normal functional state of the vascular wall.

Topics: Adult; Animals; Antihypertensive Agents; Aorta; Biflavonoids; Catechin; Cell Adhesion; Cells, Cultured; Dose-Response Relationship, Drug; Elastin; Female; Fibroblasts; Humans; In Vitro Techniques; Muscle, Smooth, Vascular; Proanthocyanidins; Swine