TiO2 Nanoflowers on Conducting Substrates Ameliorate Effective Transdifferentiation of Human Hepatic Progenitor Cells for Long‐Term Hyperglycemia Reversal in Diabetic Mice

Abstract

AbstractThe growth of 3D nanostructures on conducting substrates through a controlled hydrolysis process of titanium isopropoxide at low‐pH and higher‐pressure is reported. SEM analysis shows the formation of 300–500 nm nanorods, which are symmetrically arranged with an average size of 8–15 µm and 2–3 µm height clusters to form nanoflower‐like structures. 3D nanostructured TiO2 grown on conducting substrates shows efficient in vitro transdifferentiation of human hepatic progenitor cells (hHPCs) into insulin producing cells (T‐iPCs). The physiological functions of transdifferentiated hHPCs confirm the activation of pancreatic transcription factors, which triggers insulin exocytosis during hyperglycemic challenge. The T‐iPCs on TiO2 chips show upregulated expression of master regulator Pdx‐1, β‐cell specific marker Nkx‐6.1, and more importantly C‐peptide similar to human pancreatic β‐cells during hyperglycemic challenge. Intraperitoneally transplanted cellularized TiO2 implants show prompt recovery in blood insulin level and glucose homeostasis in streptozotocin‐induced C57BL6 mice in a glucose regulated manner without immunosuppressant. These implants provide long‐term survival and function of T‐iPCs without eliciting significant immunological reactions and fibrotic tissue/extracellular matrix deposition in vivo, which could be a better technology for developing effective therapeutic options for the management of hyperglycemia.