Reactive Oxygen Species in Physiologic and Pathologic Angiogenesis - Mechanical and Chemical Signaling in Angiogenesis - page 79

excessive ROS production or their impaired detoxification causes extended oxidative
stress, which leads to chronic, non-healing wounds with decreased angiogenesis
[ 153 ].
5 Novel Methods for Applying Reactive Species
to Stimulate Angiogenesis
Current therapeutic angiogenesis techniques lack the required clinical efficacy.
While angiogenic growth factors including VEGF [ 154 , 155 ] and FGF-2 [ 156 , 157 ]
are critical to the angiogenic process, their success depends on precise timing, dose,
and gradients [ 158 - 161 ]. Efforts to apply growth factors either in ischemic tissue,
wounds, or tissue engineered constructs to induce angiogenesis have met with
limited success [ 161 - 163 ]. ROS are known to promote angiogenesis, however
precise dosing of these species is difficult to achieve. We recently showed that non-
thermal dielectric barrier discharge (DBD) plasma could apply ROS and stimulate
angiogenesis in endothelial cells in 2D and 3D culture.
5.1 Dielectric Barrier Discharge Plasma
Plasma is an ionized gas composed of charged particles (electrons, ions), excited
atoms, molecules, radicals, and UV photons [ 2 ]. Naturally occurring plasmas
include the solar corona and lightning, and man-made plasmas are used in tele-
vision, fluorescent light bulbs, and microelectronics processing. Man-made plasma
is created with an electrical discharge and a large electric field. Electrons, being
much lighter than molecules, atoms, and ions, absorb electrical energy first. Given
sufficient time, electrons transfer a substantial part of their energy to ions, mole-
cules, and atoms through collisions. When the temperature of electrons and the
heavier plasma components equilibrates, the entire plasma becomes hot. Such
plasma is called thermal or equilibrium plasma. In non-thermal plasma, which is
far from thermal equilibrium, the electron temperature is much higher than the
heavy particle temperature. Gas in a non-thermal plasma remains close to room
temperature.
Thermal plasmas such as the argon plasma coagulator have been widely used
for blood coagulation as well as for pathological tissue removal [ 164 - 168 ].
In recent years, non-thermal plasma emerged as a novel technology for medical
applications. Since gas temperature remains close to room temperature, these
plasmas can be applied directly to cells and tissue without measurable damage
[ 169 ]. Non-thermal plasma has primarily been used to coagulate blood, sterilize
tissue and equipment, or kill bacteria and cancerous cells [ 170 - 176 ].