The Effects of Scaffold Remnants in Decellularized Tissue-Engineered Cardiovascular Constructs on the Recruitment of Blood Cells

Decellularized tissue-engineered heart valves (DTEHVs) showed remarkable results in translational animal models, leading to recellularization within hours after implantation. This is crucial to enable tissue remodeling. To investigate if the presence of scaffold remnants before implantation is responsible for the fast recellularization of DTEHVs, an in vitro mesofluidic system was used. Human granulocyte and agranulocyte fractions were isolated, stained, brought back in suspension, and implemented in the system. Three different types of biomaterials were exposed to the circulating blood cells, consisting of decellularized tissue-engineered constructs (DTECs) with or without scaffold remnants or only bare scaffold. After 5 h of testing, the granulocyte fraction depleted faster from the circulation than the agranulocyte fraction. However, only granulocytes infiltrated into the DTEC with scaffold, migrating toward the scaffold remnants. The agranulocyte population, on the other hand, was only observed on the outer surface. Active cell infiltration was associated with increased levels of matrix metalloproteinase-1 secretion in the DTEC, including scaffold remnants. Proinflammatory cytokines such as interleukin (IL)-1 alpha, IL-6, and tumor necrosis factor alpha (TNF alpha) were significantly upregulated in the DTEC without scaffold remnants. These results indicate that scaffold remnants can influence the immune response in DTEC, being responsible for rapid cell infiltration.