Medical/biological study (experimental study)

Targeted release of stromal cell-derived factor-1α by reactive oxygen species-sensitive nanoparticles results in bone marrow stromal cell chemotaxis and homing, and repair of vascular injury caused by electrical burns med./bio.

By: He F, Luo PF, Tang T, Zhang F, Fang H, Ji SZ, Sun Y, Wu GS, Pan BH, Huo ZB, Wang GY, Xia ZF

Published in: PLoS One 2018; 13 (3): e0194298

SDF-1α-PPADT nanoparticles should be investigated regarding the targeted release of SDF-1α, directional chemotaxis of bone marrow mesenchymal stem cells and repair of vascular injury caused by electrical burns in a rat model.

In a previous study, the authors used the ROS-sensitive thioketal polymer, PPADT, as a nanoparticle carrier. These nanoparticles release drugs in response to high ROS concentrations in tissue lesions, achieving the goal of targeted therapy. The nanoparticle carriers were used to encapsulate SDF (stromal cell-derived factor)-1α, forming SDF-1α-PPADT. SDF-1α is the primary chemokine to induce chemotaxis of bone marrow stromal cells (BMSCs) to a tissue lesion, where they can repair the tissue. These mechanisms were investigated in a rat and mouse modell of vascular injury caused by electrical burns.
Rats or nude mice were divided into two groups: 1) Electrical current exposure and 2) sham exposure. The type and numbers of animals, exposure durations, the time points of measurement as well as the supplementation of SDF-1α, SDF-1α-PPADT or BMSCs varied according to the investigated parameters.

Effect and mechanisms of healing of vascular injury caused by electrical burns with SDF-1α-PPADT nanoparticles

Exposure	Parameters
Exposure 1: 50–60 Hz Exposure duration: 1, 3 or 6 seconds	electric current: 180 mA ± 36 mA at 220 V (current passing through the limbs)

Exposure source	electrode
Setup	two copper electrode clips or two copper electrode plates (3 mm × 3 mm) were connected to adjustable voltage regulator (220 V used); rat or mouse was placed in prone position with limbs extended and fixed to a bench; conductive paste was smeared in the region above the ankle of both hind limbs and electrodes were applied
Sham exposure	A sham exposure was conducted.

Measurand	Value	Type	Method	Mass	Remarks
cf. remarks	-	maximum	measured	-	electric current: 180 mA ± 36 mA at 220 V (current passing through the limbs)

Exposed system:

morphol./histopathol. changes: histopathological changes of wound tissue (hematoxylin-eosin stain and immunohistochemical stain of CD31 (marker for angiogenesis); microscopy), reactive oxygen species in wound tissue (fluorescence microscopy)
molecular biosynthesis: gene expression of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase in wound tissue (RT-PCR), protein expression of SDF-1α in wound tissue (ELISA)
verification of ROS-sensitive targeted release of SDF-1α from nanoparticels in mice in vivo (injection of fluorescence-labeled SDF-1α or SDF-1α-PPADT; fluorescence imaging system) and in wound tissue in vitro (injection of SDF-1α or SDF-1α-PPADT; ELISA); directional chemotaxis and homing of BMSCs to wound tissue (injection of fluorescence-labeled BMSCs and SDF-1α or SDF-1α-PPADT and immunofluorescence stain of CD31; fluorescence microscopy); histopathological effects of SDF-1α-PPADT nanoparticles on vascular repair (injection of rats with SDF-1α or SDF-1α-PPADT, hematoxylin-eosin stain and immunohistochemical stain of CD31 of wound tissue; microscopy)

Investigated system:

Time of investigation:

Exposure to electric current for 6 s could damage vascular endothelial cells, strip off the inner layer of vessels and significantly elevate the local level of ROS and antioxidative enzymes compared to sham exposure. Exposure to electric current for 1 s and 3 s led to significant increase of SDF-1α in wound tissue compared to the sham exposure group, while exposure to electric current for 6 s did not show significant differences.
After injection of fluorescence-labeled SDF-1α-PPADT nanoparticles, the distribution of fluorescence suggested that SDF-1α was distributed primarily at the injury site, and the local SDF-1α levels increased significantly in the exposure group compared to the sham exposure group. Seven days after the electrical injury, aggregation of fluorescence-labeled BMSCs at the injury site was observed in rats with nanoparticles injection. Ten days after the elctrical injury, the endothelial cell arrangement was better organized and continuous, with relatively intact vascular morphology and more blood vessels compared to rats with electrical injury but without nanoparticel injection.
The authors conclude that SDF-1α-PPADT nanoparticles targeted the SDF-1α release at the site of injury, directed BMSC chemotaxis and homing and promoted vascular repair in response to electrical burns in a rat model.

Study character:

Saputro I et al. (2018): The effect of oral N-acetylcystein on prevention of extensive tissue destruction in electrical burn injury
Prindeze NJ et al. (2014): Regional Neurovascular Inflammation and Apoptosis Are Detected After Electrical Contact Injury
Shupp JW et al. (2012): Examination of local and systemic in vivo responses to electrical injury using an electrical burn delivery system
Laberge LC et al. (1984): Experimental electrical burns: low voltage