Wound Dressings Based on Rubidium-Doped Bioactive Glass Nanospheres Promote Diabetic Wound Healing.

An improved Stober method was successfully adopted to synthesize the rubidium-doped bioactive glass nanospheres (Rb-BGNs) with excellent homogeneity and integrity. The in vitro results show that the ionic solvent product of Rb-BGNs stimulated human umbilical vein endothelial cells (HUVECs) to proliferate, migrate and promote tubule forming by inducing HIF-1 alpha-driven angiogenesis-related molecules. The ionic dissolution product of Rb-BGNs also promoted the proliferation and migration of both the fibroblasts (FBs) and human immortal keratinocytes (HaCaTs). Meanwhile, growth-promoting factors (such as TGF-beta 1, FGF2, PDGF, and EGF) and ERK/P38 signaling pathways of FBs and HaCaTs were activated by the ionic dissolution product of Rb-BGNs. In vivo study demonstrated that Rb-BGNs could improve wound healing through the synergetic effect on promoting angiogenesis, re-epithelialization as well as collagen deposition on wound surface of diabetic ulcer. Furthermore, EGF loaded Rb-BGNs were freeze-dried for further study. The results show that the EGF loaded Rb-BGNs improved wound healing better than Rb-BGNs, indicating that Rb-BGNs not only have the ability to promote wound healing itself, but also can deliver other drugs to synergistically facilitate the process. Therefore, our work proves that Rb-BGNs is a promising nanoparticle filler for wound healing of diabetic ulcer.