Cerium-Containing Bioactive Glasses Promote In Vitro Lymphangiogenesis.

Hanyu Xie,Geng Wu,Rongyao Xu,Aldo R Boccaccini,Sha Sha,Kai Zheng,Hongbing Jiang,Lingbo Lu

doi:10.3390/pharmaceutics14020225

Hanyu Xie, Geng Wu + Show 6 more

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https://doi.org/10.3390/pharmaceutics14020225

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Abstract

The lymphatic system is crucial for the regeneration of many tissues due to its fundamental role in immune cell trafficking, protein transport, and tissue homeostasis maintenance. Strategies stimulating lymphangiogenesis can provide new therapeutic approaches for tissue repair and regeneration (e.g., chronic wound healing). Here, we explored the effects of cerium-containing mesoporous bioactive glass nanoparticles (Ce-MBGNs) on lymphangiogenesis. The results showed that the extracts of Ce-MBGNs (1, 5, or 10 wt/v%) were non-cytotoxic toward lymphatic endothelial cells (LECs), while they enhanced the proliferation of LECs. Moreover, as evidenced by the scratch wound healing and Transwell migration assays, conditioned media containing the extract of Ce-MBGNs (1 wt/v%) could enhance the migration of LECs in comparison to the blank control and the media containing vascular endothelial growth factor-C (VEGF-C, 50 ng/mL). Additionally, a tube-formation assay using LECs showed that the extract of Ce-MBGNs (1 wt/v%) promoted lymphatic vascular network formation. Western blot results suggested that Ce-MBGNs could induce lymphangiogenesis probably through the HIF-1α/VEGFR-3 pathway. Our study for the first time showed the effects of Ce-MBGNs on stimulating lymphangiogenesis in vitro, highlighting the potential of Ce-MBGNs for wound healing.

Highlights

Wound healing is a complex process, which covers four overlapping stages, i.e., hemostasis, inflammation, proliferation, and remodeling [1]
Our results revealed that the extracts of Ce-MBGNs (1, 5, or 10 wt/v% in DMEM) were noncytotoxic against lymphatic endothelial cells (LECs)
The extracts of Ce-MBGNs (1 wt/v%) could enhance the migration of LECs and promote lymphatic vascular network formation compared to the blank control and the vascular endothelial growth factor (VEGF)-C (50 ng/mL) group

Summary

Introduction

Wound healing is a complex process, which covers four overlapping stages, i.e., hemostasis, inflammation, proliferation, and remodeling [1]. Some undesired conditions, for example, infection and inflammation, can cause the failure of wound healing or a prolonged healing time. Disruption of the four stages can cause an extended wound healing period resulting in a chronic wound [1]. Suffering from chronic wounds can remarkably reduce the living quality of patients, which has been a considerable issue for global healthcare. Healing of chronic wounds (e.g., ulcers caused by peripheral vascular disease and diabetes) remains an unsolved medical challenge

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