Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
College of Chemistry and Materials Science, Shanghai Normal University, Shanghai 200234, China.
ACS Nano. 2023 Oct 24;17(20):19652-19666. doi: 10.1021/acsnano.3c02561. Epub 2023 Oct 11.
Electrical stimulation therapy (EST) has been established as an effective strategy to accelerate wound healing by stimulating cell proliferation and migration, ultimately promoting re-epithelialization and vascularization, two key processes that significantly influence the rate of wound healing. Phosphatase and tensin homologue (PTEN), a widely expressed protein in somatic cells, works as a "brake" regulating cell differentiation, proliferation, and migration. Given that this "brake" also works in cell electrical responses, there is a hypothesis that PTEN inhibition may amplify the efficacy of EST in wound treatment. However, long-term inhibition of PTEN may result in DNA damage and reduce DNA repair, which poses a significant challenge to the safe use of PTEN inhibitors. To address this issue, we developed a system that combines PTEN inhibitor loaded electro-responsive hydrogel (BPV@PCP) with a wearable direct current pulse piezoelectric nanogenerator (PENG). The PENG converts the rat's motions into electric fields that synchronously charge the wound edge tissue and BPV@PCP. Electric field intensity was lower when the rat was quiet or anesthetized, which is insufficient to trigger an effective PTEN inhibitor release. However, when the rat was in action, the electric field intensity exceeded 625 mV/mm, resulting in a rapid drug release. This on-demand PTEN inhibition accelerated wound healing by amplifying cell electric responsiveness while avoiding negative effects associated with continuous overinhibition of PTEN. Notably, this system improves vascularization not only by improving endothelial cell electric responsiveness but also through the paracrine pathway, in which electrical stimulation and PTEN inhibition synergically promote VEGF secretion.
电刺激疗法 (EST) 已被确立为一种通过刺激细胞增殖和迁移来加速伤口愈合的有效策略，最终促进再上皮化和血管生成，这两个关键过程显著影响伤口愈合的速度。磷酸酶和张力蛋白同源物 (PTEN) 是一种在体细胞中广泛表达的蛋白质，作为调节细胞分化、增殖和迁移的“刹车”发挥作用。由于这个“刹车”也作用于细胞的电反应，因此有一个假设，即 PTEN 抑制可能会增强 EST 在伤口治疗中的效果。然而，PTEN 的长期抑制可能会导致 DNA 损伤并减少 DNA 修复，这对 PTEN 抑制剂的安全使用构成了重大挑战。为了解决这个问题，我们开发了一种系统，将负载 PTEN 抑制剂的电响应水凝胶 (BPV@PCP) 与可穿戴的直流脉冲压电纳米发电机 (PENG) 结合在一起。PENG 将大鼠的运动转化为电场，同步为伤口边缘组织和 BPV@PCP 充电。当大鼠安静或麻醉时，电场强度较低，不足以引发有效的 PTEN 抑制剂释放。然而，当大鼠活动时，电场强度超过 625 mV/mm，导致药物快速释放。这种按需 PTEN 抑制通过放大细胞的电反应来加速伤口愈合，同时避免了与 PTEN 持续过度抑制相关的负面影响。值得注意的是，该系统不仅通过改善内皮细胞的电反应，还通过旁分泌途径来改善血管生成，其中电刺激和 PTEN 抑制协同促进 VEGF 的分泌。
