Nanofabricated Devices and Nanomedicine Approaches for Wound Healing

用于伤口愈合的纳米制造设备和纳米医学方法

• 批准号: 10888600
• 负责人: Yi Xuan
• 金额: $ 15.59万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10888600
• 关键词: Acceleration; Actins; Address; Adopted; Adult; Animal Model; Biological; Biology; Biomedical Research; Blood Vessels; Cells; Characteristics; Clinical; Clinical Trials; Cytoskeletal Modeling; Dedications; Devices; Diabetic mouse; Disease; Drug Delivery Systems; Electrophysiology (science); Encapsulated; Engineering; Ensure; Gene Transfer; Generations; Genomics; Goals; Health; Human; Immune; In Vitro; K-Series Research Career Programs; Label; Laboratories; Learning; Lipids; Mediator; Medicine; Mentors; Messenger RNA; Methods; MicroRNAs; Microtubules; Modification; Multivesicular Body; Mus; Nanotechnology; Neurons; Nucleic Acids; Oligonucleotides; Plasmids; Preclinical Testing; Procedures; Proteins; RNA; Regenerative Medicine; Reporting; Research; Research Proposals; Risk; Role; Science; Signal Transduction; Skin; Skin wound healing; Structure; Technology; Technology Transfer; Testing; Therapeutic; Tissues; Training; United States National Institutes of Health; Work; biomarker discovery; career; clinically significant; design; diabetic ulcer; diabetic wound healing; efficacy testing; electric field; engineered exosomes; exosome; improved; in vivo; intercellular communication; interest; nano; nanocarrier; nanomedicine; nanoscience; nanotransfection; neurogenesis; new technology; paracrine; pre-clinical; rab GTP-Binding Proteins; recruit; research study; skills; skin wound; technology platform; tissue regeneration; vasculogenesis; wound closure; wound healing

Project Summary/Abstract This mentored research proposal seeks to aims establish a laboratory of an engineer and nanoscientist in biomedical research. The scientific focus of this proposal is on tissue nanotransfection (TNT), an electromotive gene transfer technology that delivers plasmids, RNA and oligonucleotides to the live tissue in vivo. This technology was the first to achieve non-viral in vivo reprograming of the skin to functional blood vessels (iV, induced vasculogenesis) or to electrophysiologically active neural cells (iN, induced neuritogenesis) under immune survillence using a nanoelectroporation approach that does not pose the risk of genomic integration or transformation. TNT facilitates packaging of reprogramming cargo into biological nano carrier called exosome. Although the feasibility of this approach has been tested in murine skin, its application in pre-clinical setting is yet to be tested. The proposed work focuses on a new design of TNT chip that can be leveraged for release of endogenous engineered exosomes in vivo for therapeutic purposes in both diabetic mice and humans. Such approach was adopted to ensure high clinical significance. The project includes the following three aims. ?Aim 1: Nanoelectroporation induces release of exosome from cells. ?1.1: Nanoelectroporation increases cellular cytoskeletal reorganization and recruitment of Rab-GTPase at the microtubules for transfer of multivesicular bodies to the actin-rich cortex for release of exosome. ?1.2: Nanoelectroporation can be used as a method to package endogenous mRNA and miRNA for release via exosome. ?Aim 2: Test the efficacy of tissue nanotransfection induced engineered exosome in accelerating diabetic wound closure. ?2.1: Design of plasmids for cell-specific packaging of mRNA in vivo. ?2.2: In vivo cell specific mRNA packaging within exosome via TNT accelerates diabetic wound healing. ?Aim 3: Develop human scale TNT2.1 chip for preliminary preclinical testing.

项目总结/摘要 这项指导研究提案旨在建立一个工程师和纳米科学家的实验室， 生物医学研究这项提案的科学重点是组织纳米转染（TNT），一种电动 基因转移技术，将质粒、RNA和寡核苷酸递送到体内活组织。这 技术是第一个实现皮肤到功能性血管的非病毒体内重编程的技术（IV， 诱导的血管发生）或电生理活性神经细胞（iN，诱导的神经突发生）， 使用纳米电穿孔方法进行免疫监测，不会造成基因组整合的风险，或 转型TNT有助于将重编程货物包装到称为外泌体的生物纳米载体中。 虽然这种方法的可行性已经在小鼠皮肤中进行了测试，但其在临床前环境中的应用还有待进一步研究。 还有待检验拟议的工作重点是TNT芯片的新设计，可用于发布 内源性工程化外泌体在体内用于糖尿病小鼠和人类的治疗目的。等 方法，以确保高的临床意义。该项目包括以下三个目标。?目的 1：纳米电穿孔诱导外泌体从细胞释放。? 1.1：纳米电穿孔增加细胞 细胞骨架重组和Rab-GTdR在微管的募集用于多泡细胞的转移 将细胞体运送到富含肌动蛋白的皮质以释放外泌体。? 1.2：纳米电穿孔可用作一种方法， 包装内源性mRNA和miRNA以通过外泌体释放。?目的2：测试组织的功效 纳米转染诱导的工程化外泌体加速糖尿病伤口闭合。? 2.1：质粒的设计 用于体内mRNA的细胞特异性包装。? 2.2：通过TNT在外来体内细胞特异性mRNA包装 加速糖尿病伤口愈合?目的3：开发人体规模的TNT2.1芯片进行初步的临床前测试。

项目成果

Myogenic tissue nanotransfection improves muscle torque recovery following volumetric muscle loss.

• DOI: 10.1038/s41536-022-00259-y
• 发表时间: 2022-10-20
• 期刊: NPJ REGENERATIVE MEDICINE
• 影响因子: 7.2
• 作者: Clark, Andrew;Ghatak, Subhadip;Guda, Poornachander Reddy;El Masry, Mohamed S.;Xuan, Yi;Sato, Amy Y.;Bellido, Teresita;Sen, Chandan K.
• 通讯作者: Sen, Chandan K.