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/文摘

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.