慢性傷口不僅帶給國家龐大的醫療支出成本，亦會對患者產生身心理上的負面影響，隨著老年人口日益增加，慢性傷口的影響也日趨嚴重。而超音波具非侵入性且不危害人體的特性，成了治療慢性傷口中擁有強大潛力的方法之一。先前的研究也顯示出治療超音波確實可以加速傷口癒合，不論是在細胞、動物甚至是臨床試驗上。另外，為避免超音波探頭與傷口直接接觸，將使用非接觸式探頭進行實驗。本研究利用非接觸式低強度脈衝式超音波刺激人類表皮角質形成細胞 (HaCaT) 以觀察細胞爬行與鈣離子依賴性轉錄因子的活化，除了建構有效的超音波刺激參數，亦研究其潛在與鈣離子相關的分子機制。
在接觸式探頭研究中，使用頻率為1MHz的非聚焦探頭，刺激強度為40, 200 mW/cm2且持續15分鐘；在非接觸式探頭研究中，使用頻率為0.5 MHz的聚焦探頭，刺激強度為30 mW/cm2且持續15分鐘。除了研究細胞爬行與鈣離子依賴性轉錄因子的活化外，也對細胞進行細胞活力及細胞增生檢測實驗，以及利用鈣離子通道抑制劑與鈣離子指示劑進行進一步的驗證。
研究結果顯示不論是接觸式探頭或非接觸式探頭，低強度脈衝式超音波皆可以顯著加速細胞爬行並活化鈣離子依賴性轉錄因子CREB與NFAT1。此外，在非接觸式探頭研究中，發現該刺激強度並不會造成細胞死亡且在細胞爬行過程中並不包含細胞增生現象。除此之外，在超音波刺激過程中，細胞內鈣離子濃度亦明顯上升。最後，鈣離子通道抑制劑有效降低超音波對HaCaT細胞的影響，抑制由 LIPUS 誘發的 Ca2+ 依賴性轉錄因子活化和細胞爬行。

Chronic wounds not only bring about substantial healthcare expenditures to the country, but also lead to a negative physical and psychological condition to patients. As the elderly population increases, the impact of chronic wounds becomes more and more severe. Since the non-invasive and harmless characteristic, ultrasound shows great potential in treating chronic wounds. Previous studies have shown ultrasound can accelerate wound healing in in vitro, in vivo, and clinical studies. In addition, to avoid directly contacting the wound, a non-contact transducer was used. In this study, utilizing LIPUS stimulation on human epidermal keratinocytes (HaCaT) to observe cell migration and activation of calcium (Ca2+)-dependent transcription factors. The aim is to construct effective stimulation parameters, and its Ca2+-related signaling mechanism. In contact transducer study, using a 1 MHz transducer with an intensity of 40, 200 mW/cm2 for 15 min stimulation; in non-contact transducer study, using a 0.5 MHz focused transducer with an intensity of 30 mW/cm2 for 15 min stimulation. Moreover, cell viability and cell proliferation experiments were also performed. The results demonstrated LIPUS can notably increase cell migration and activate the Ca2+-dependent transcription factors CREB and NFAT1 by two types of transducers. Furthermore, in non-contact transducer study, the stimulation intensity would not cause cell death, and without cell proliferation during cell migration process. Additionally, the intracellular Ca2+ level increases significantly upon LIPUS stimulation. Finally, Ca2+ channel blockers effectively inhibited activation of Ca2+-dependent transcription factors and cell migration induced by LIPUS.

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