Hydrogel Composite Incorporating Deferoxamine-Loaded Gelatin-Based Microspheres Enhance Angiogenesis Ability of Dental Pulp Stem Cells

Fast reconstruction of the pulpal vasculature is crucial for effective pulp regeneration. Dental pulp stem cells (DPSCs) are promising candidates for pulp regeneration because of their potential for multilineage differentiation and vasculogenic properties. Deferoxamine (DFO) has been shown to stimulate angiogenesis during wound healing and bone regeneration; however, the effects of DFO on the angiogenic potential of DPSCs remain unknown. Moreover, its usefulness is restricted by a limited half-life and challenges in achieving localized tissue enrichment. This study aimed to develop a sustained-release injectable hydrogel composite as a drug delivery system and to investigate its influence on DPSCs. Herein, gelatin-based microspheres (GMSs) were loaded with DFO, and temperature-sensitive injectable hydrogels incorporating collagen and chitosan were synthesized to enable controlled DFO release. The experimental findings demonstrated that the DFO-loaded GMSs (DFO-GMSs) hydrogel composite possessed favorable physical properties and biocompatibility, enabling sustained DFO delivery for up to 15 days. DFO effectively stimulated DPSC migration, promoted the secretion of angiogenesis-related factors, and induced tube formation in vitro. These results suggest that the DFO-GMSs hydrogel composite significantly increased the migration and angiogenic potential of DPSCs, highlighting its promise for tissue regeneration applications.