Botulinum Toxin A: Dose-dependent Effect on Reepithelialization and Angiogenesis

Area of Science:

• Cellular Biology
• Dermatology
• Plastic Surgery

Background:

• Botulinum (neuro)toxin A (BoNT) is utilized in plastic and reconstructive surgery for aesthetic purposes, pain management, hyperhidrosis, and notably, to improve wound healing and minimize scarring.
• While clinical applications are established, the precise cellular mechanisms underlying BoNT's effects on wound healing remain incompletely understood.

Purpose of the Study:

• To investigate the in vitro effects of botulinum (neuro)toxin A (BoNT) on primary human keratinocytes and endothelial cells, key players in the wound healing process.
• To assess the impact of varying BoNT concentrations on cellular proliferation, migration, and the angiogenic potential of endothelial cells.

Main Methods:

• Primary human keratinocytes and endothelial cells were cultured and treated with three concentrations of BoNT: low (1 IU/mL), medium (10 IU/mL), and high (20 IU/mL).
• Cellular proliferation and migration assays were performed for both cell types.
• The angiogenic behavior of endothelial cells was evaluated in vitro.

Main Results:

• A high concentration of BoNT (20 IU/mL) significantly inhibited the proliferation and migration of keratinocytes.
• Endothelial cell proliferation and migration were not adversely affected by the tested BoNT concentrations.
• High BoNT concentrations (20 IU/mL) reduced in vitro angiogenesis, while low concentrations (1 IU/mL) appeared to promote endothelial cell sprouting.

Conclusions:

• High concentrations of botulinum (neuro)toxin A can negatively impact wound closure by impairing keratinocyte functions essential for healing.
• Botulinum (neuro)toxin A at 20 IU/mL constrains in vitro blood vessel formation but does not affect endothelial cell proliferation or migration.
• The findings suggest a dose-dependent effect of BoNT on wound healing cellular processes, with potential benefits at low concentrations and detrimental effects at high concentrations.