Dr. Zhao Research Lab-Research Focus
Our research is aimed toward improving wound healing and regeneration of damaged or diseased tissues.
Our current work focuses on:
- The role naturally occurring electric fields or electric currents in wound healing and tissue regeneration.
- Development of therapies to electrically stimulate and direct wound healing and tissue regeneration.
- Targeting stem cell migration.
Endogenous wound electric fields and electric stimulation in wound healing
Delayed or non-healing wounds pose an immense health and economic problem with an estimated cost to the US health system in excess of $20 billion. Effective wound healing requires precisely regulated cell movement and tissue growth. Epithelial wound healing consists of a series of ordered events including epithelial cell spreading, migration, proliferation and differentiation. However, the basic mechanisms of epithelial repair are not fully understood. Impaired re-epithelialization and persistent epithelial defects are characteristic of chronic wounds in the elderly, decubitus ulcers, and venous stasis ulcers of the skin.
Endogenous wound electric fields (EFs) were discovered centuries ago. Using modern techniques (e.g. vibrating probes or glass microelectrodes), the existence of these naturally occurring EFs has been confirmed in a variety of tissues including skin and cornea.It has long been suggested that endogenous EFs might have a role in wound healing. These EFs have also been implicated in development and regeneration; electric currents have been detected and experimental disruption of the EFs causes developmental abnormalities and substantially impaired regeneration.
Clues that initiate epithelial cells to grow directionally into the wound include injury stimulation, contact inhibition release, wound void and chemical substances released from inflammatory cells and injured cells. Both keratinocytes and corneal epithelial cells have been shown to respond robustly to small direct-current EFs with strength within the range that have been measured at wounds. Most importantly, electric signals of physiological strength are a predominant guidance cue directing migration of corneal epithelial cells (CECs) in wound healing against other well-accepted directional cues (Zhao et al., Nature, 2006 442: 457-460).
There are many examples of clinical use of electric stimulation to promote injury repair, such as in non-union of bones, non-healing skin ulcers, and spinal injuries. Animal experiments and clinical trials have gradually established the efficacy of such a treatment. Clinical application of electric stimulation appears to have beneficial effects in wound healing, especially for intractable wounds.
Due to its apparent benefits, electrical stimulation has recently been approved in the US, for Medicare coverage in treatment of refractory chronic wounds (chronic Stage III or Stage IV pressure ulcers, arterial ulcers, diabetic ulcers and venous stasis ulcers). Unfortunately, results and conclusions from using electric stimulation in clinical trials are inconsistent. Not a single electrical stimulation device has been approved or received pre-market approval by the FDA for wound healing. Applicability of electric stimulation in management of wound healing is greatly hindered by lack of in-depth scientific understanding and approved devices.