Investigating the Impact of Titanium Dioxide Nanoparticles on Wound Healing

Approaches in the study of wound healing attempts to promote and accelerate either of the four stages in wound healing: homeostasis, inflammation, proliferation and remodeling. An approach in developing wound dressing is titanium dioxide (TiO2) nanotechnology-based interventions, where its antimicrobial properties are utilized in creating nanocomposite wound dressings. While there has been many studies in accelerating the inflammation phase, little has been researched on promoting the proliferation and remodeling phase of wound healing. Thus, this study focuses on the TiO2 nanoparticles on human umbilical vein endothelial cells (HUVEC) angiogenesis and impact of exposed rutile TiO2 nanoparticles on human skin organotypic was studied on a cellular and tissue level.

To test for TiO2 cytotoxicity, cells were treated at a concentration of 0.4 mg/mL rutile TiO2 particles for 24 hours prior to the tests. Fibroblast and keratinocyte cell proliferation assays were then evaluated for 5 days after treatment. Data shows that the presence of TiO2 nanoparticles did not significantly impact the proliferate rate of either keratinocyte or fibroblast.

For HUVEC angiogenesis assay, after the TiO2 treatments, HUVECS were sorted through fluorescence activated cell sorting. Cells sorted with a high scattering angle window were assumed to have an increase in TiO2 uptake. HUVECs with and without TiO2 underwent 18 hours of vascular network formation on Matrigel. Quantification of network formation of HUVECs cells using EVOS microscope shows greater vessel network density in the treated sample, suggesting promotion of angiogenesis.

Lastly, wound healing in treatments of TiO2 nude mice skin grafts were studied. 8 millimeter diameter puncture wounds was inflicted posteriorly on both mice A) with transplanted vascularized autografts as control and mice B) 20 microliters of 0.4 mg/mL TiO2 placed onto the wound followed by the transplantation of vascularized autograft. Through post-autograft histology of both mice, TiO2 did not affect the fibroblast’s ability to support the epidermis and there were nanoparticles aggregation near the stratum corneum for TiO2 treated skin equivalents.

In conclusion, the data demonstrated that TiO2 nanoparticles do not interfere with the skin wound healing process, rather promote angiogenesis. TiO2 not only did not have a negative impact on the functionality of the epidermis, but also showed evidence that TiO2 can be removed from tissue through epidermis differentiation.