Impact of\nDiabetic Condition on the Remodeling of\nIn Situ Tissue-Engineered Heart Valves

Most in situ tissue-engineered heart valve (TEHV) evaluation\nstudies\nare conducted in a healthy physical environment, which cannot accurately\nreflect the specific characteristics of patients. In this study, we\nestablished a diabetic rabbit model and implanted decellularized extracellular\nmatrix (dECM) into the abdominal aorta of rabbits through interventional\nsurgery with a follow-up period of 8 weeks. The results indicated\nthat dECM implants in diabetic rabbits exhibited poorer endothelialization\nand more severe fibrosis compared to those in healthy animals. Furthermore,\nmechanistic studies revealed that high glucose induced endothelial\ncell (EC) apoptosis and impeded their proliferation and migration,\naccompanied by an increase in reactive oxygen species (ROS) concentration\nand a decrease in the nitric oxide (NO) level. High glucose also led\nto elevated ROS levels and an increased expression of inflammatory\nfactors and transforming growth factor β1 (TGF-β1) in\nmacrophages, contributing to fibrosis. These findings suggest that\noxidative-stress-mediated mechanisms are likely the primary pathways\naffecting heart valve repair and regeneration under diabetic conditions.\nTherefore, future design and evaluation of TEHVs may concern more\npatient-specific circumstances.