Among the patients treated by Rehabilitation Medicine are those with decubitus and leg ulcers. These have significant morbidity, mortality and often are resistant to conventional treatment. The efficacy of electrotherapy is unsettled after decades of use and the possibility remains that a natural source of electricity within wounds(i.e., the """"""""skin battery"""""""") may promote healing. We propose to elaborate the observation that fibroblasts decrease protein synthesis if exposed to electric fields comparable to endogenous fields. For this purpose, human dermal fibroblasts in type I collagen dermal """"""""equivalent"""""""" matrices (DEM) are exposed to ionic currents. Initial results from our DEM model are promising. They suggests an increase in proliferation to electric fields of 20 mv/m, 10Hz.(p,01). (Most often synthesis and proliferation are reciprocal). Employing the same model, we propose a comprehensive study of the biochemical response of the DEM model to these electric fields. We plan radioisotope assays for DNA, proteoglycans, collagen, fibronectin and collagenase. Identifying the process most susceptible to electric effect, we will survey response to amplitudes and frequencies within the endogenous range. If the skin battery is important to wound healing, cells should be most sensitive at 1-10 Hz (i.e., down to 5-20 m/m). Early after wounding, fibroblasts undergo fibroplasia, and synthesis of proteoglycans and fibronectin. Later, collagen synthesis and neoangiogenisis peak. We will investigate the biochemical response of fibroblasts in DEM from 0 to 14 days after stimulation to see if these biosynthetic transformations occur in vitro. If they do, we will have compelling evidence that the skin battery help mediates the response in vivo. Lastly, we will investigate electric effects on early intracellular events that ultimately lead to proliferation and/or synthesis.
| Binhi, V N; Goldman, R J (2000) Ion-protein dissociation predicts 'windows' in electric field-induced wound-cell proliferation. Biochim Biophys Acta 1474:147-56 |
| Cheng, K; Goldman, R J (1998) Electric fields and proliferation in a dermal wound model: cell cycle kinetics. Bioelectromagnetics 19:68-74 |
