Biodegradable and Biocompatible Piezoelectric Nanofiber Mat for Wound Dressing

摘要 由疾病和身体伤害引起的慢性和不愈合的伤口是一个主要的医学问题 国际吧伤口敷料是伤口治疗的重要组成部分。他们广泛地 开发以同时获得促进（1）止血，（2）细菌预防， (3)隔热，（4）渗出物吸收性，和（5）在受伤或受损组织中的细胞/水分保持。 尽管有许多令人鼓舞的结果，但目前的伤口敷料仍难以拥有所有期望的特性。 使用超声波、负压、水疗法和电的物理刺激也有报道 作为伤口敷料的补充物，以促进愈合率。然而，所有这些辅助方法仍然处于 不成熟阶段，临床应用有限。纳米纤维垫似乎是一种有吸引力的 用于伤口敷料的平台。由于其固有的纳米结构具有高的表面积与体积比和高的介电常数， 多孔性，该垫能够增强止血，出色的细胞和水分保留，以及高吸收性 渗出液。假设，一个混合的敷料与物理刺激，如超声波 并且电疗将提供协同效应以显著促进伤口愈合。在这方面，委员会注意到， PI最近开发了一种新的生物可吸收和生物相容性的压电聚合物聚L-乳酸 酸或PLLA（PNAS，115（5）909-914，2018），其可以将机械变形转化为有用的电力 刺激伤口愈合在这里，我们首次提出了一种独特的方法， 可生物降解的PLLA压电陶瓷支架，它受到非声压力， 侵入性超声（US），以促进伤口愈合。我们的主要假设/科学前提是， 压电-PLLA纳米纤维在施加US下将产生有用的表面电荷， 纳米纤维的伤口愈合特性将产生协同效应，以抑制细菌感染， 促进成纤维细胞增殖，使胶原蛋白快速形成， 上皮形成，从而促进伤口愈合。为了证明这一前提，该项目将有三个 具体目标：目标1是表征压电表面电荷，由静电纺丝PLLA微球产生， 在体外施加US。目的二是研究成纤维细胞和上皮细胞在压电陶瓷上的活性 PLLA纳米纤维在体外具有超声波刺激等伤口敷料性能。 目的3是证明使用这种防粘连垫和应用US促进全层愈合 体内皮肤创伤。

Abstract Chronic and non-healing wounds, caused by diseases and physical injuries, are a major medical problem worldwide. Wound dressings are important components for wound treatment. They have been extensively developed to simultaneously obtain various capabilities which facilitate (1) hemostasis, (2) bacterial prevention, (3) thermal insulation, (4) exudate absorbability, and (5) cell/moisture retention in injured or damaged tissues. Despite many encouraging results, current wound dressings still struggle to possess all of the desired properties. Physical stimulations using ultrasound, negative pressures, hydrotherapy and electricity have been also reported as supplements to wound dressing for promoting healing rate. Yet, all of these adjuvant approaches are still at immature stages with limited applications in clinical settings. Nanofiber mats have appeared to be an appealing platform for wound dressing. Due to their inherent nanostructures with high surface-to-volume ratio and high porosity, the mats enable an enhanced hemostasis, excellent retention of cells and moisture, and high absorption of exudate. Hypothetically, a hybridization of nanofiber dressings with physical stimulations such as ultrasound and electrical therapies will provide a synergistic effect to significantly promote wound healing. In this regard, The PI has recently developed a new bioresorbable and biocompatible piezoelectric polymer of poly-L-lactide acid or PLLA (PNAS, 115 (5) 909-914, 2018), which can convert mechanical deformation into useful electricity for stimulating wound healing. Here we propose for the first time a unique approach, utilizing a new biodegradable piezoelectric nanofiber scaffold of PLLA, which is subjected to acoustic-pressure of non- invasive ultrasound (US), to enhance wound healing. Our main hypothesis/scientific premise is that the piezo-PLLA nanofibers under applied US will generate useful surface charge which together with excellent wound-healing properties of the nanofibers will create a synergistic effect to suppress bacterial infection, facilitate exudate drainage, promote proliferation of fibroblasts and enable rapid formation of collagen for re- epithelialization, consequently promoting wound healing. To demonstrate this premise, the project will have three specific aims; Aim 1 is to characterize piezoelectric surface charge, generated by the electrospun PLLA nanofiber mat under applied US in vitro. Aim 2 is to assess activities of fibroblast and epithelial-cells on the piezoelectric PLLA nanofiber mat with ultrasound stimulation and other wound dressing properties of the nanofibers in vitro. And aim 3 is to demonstrate the use of this nanofiber mat and applied US for promoting healing of full-thickness skin wound in vivo.