Functional cobalt-doped hydrogel scaffold enhances concurrent vascularization and neurogenesis.

Achieving functional tissue regeneration hinges on the coordinated growth of intricate blood vessels and nerves within the defect area. However, current strategies do not offer a reliable and effective way to fulfill this critical need. To address this challenge, a three-dimensional (3D) gelatin methacryloyl-multi-walled carbon nanotube/cobalt (GelMA-MWCNTs/Co) hydrogel with controlled release of cobalt (Co) ions was developed for hypoxia-mimicking and dual beneficial effects on promoting vasculogenesis and neurogenesis. GelMA-MWCNTs/Co hydrogel exhibited sustained release of Co ions, promoting laden cell viability and long-term cell survival. GelMA-MWCNTs/Co hydrogel effectively enhanced human umbilical vein endothelial cells (HUVECs) vasculogenesis when cocultured with stem cells from apical papilla (SCAP). Moreover, this hydrogel facilitated the interaction between the pre-formed vascular and neural-like structures generated by electrical stimulation-induced SCAP (iSCAP). Furthermore, our in vivo study revealed that the GelMA-MWCNTs/Co hydrogel remarkably enhanced neovascularization and accelerated anastomosis with the host vasculature. The pre-vascularized scaffolds boosted the presence of neural differentiated SCAP in the regenerated tissue. This study provided proof of integrating functional Co ions release materials and dental-derived stem cells within a hydrogel scaffold as a promising potential for achieving simultaneous vascularization and neurogenesis.