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Photoacoustic and epigenetic nerve scaffold for nerve regeneration

用于神经再生的光声和表观遗传神经支架

基本信息

批准号：
10445552
负责人：
Jian Yang
金额：
$ 42.94万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-18 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10445552
关键词：
Affect Anatomy Ankle Athletic Injuries Autologous Transplantation Biochemical Biocompatible Materials Biomechanics Blood Vessels Bone Screws Caliber Cells Citrates Clinical Cues Data Defect Development Diagnosis Disadvantaged Dose Elastomers Elbow Epigenetic Process Evolution FDA approved Fiber Folic Acid Genes Goals Gold Half-Life Hemoglobin Image In Situ Injury Knee Light Maps Medical Device Methodology Modality Monitor Morbidity - disease rate Morphogenesis Natural regeneration Nerve Nerve Regeneration Neuroma Neuronal Differentiation Neurons Numbness Operative Surgical Procedures Orthopedics Outcome Parents Peripheral Peripheral Nerves Peripheral nerve injury Persons Polyesters Polymers Postoperative Period Process Rattus Recovery of Function Regenerative capacity Regulation Research Resistance Role Series Shoulder Site Speed Spinal Ganglia Structure Surgical sutures Time Tissues Ultrasonography United States Urethane Vitamins Wrist Yang absorption base biodegradable polymer bioimaging cell regeneration crosslink design foot implantation improved in situ imaging in vivo in vivo evaluation injury and repair innovation interest migration nerve gap neuron regeneration novel peripheral nerve regeneration photoacoustic imaging regenerative repaired scaffold sciatic nerve sciatic nerve injury success tissue oxygenation

项目摘要

Project Summary This proposal aims to uncover the underexplored epigenetic and biomechanical roles of folate (FA, Vitamin B9) for neuronal morphogenesis and develop novel epigenetically stimulating, biodegradable, and photoacoustic nerve guidance conduits (NGCs) for the repair of critical-sized peripheral nerve (PN) defects. The hypotheses are that (1) local delivery of an inexpensive and stable (half-life of over 100 days) folate (also known as vitamin B9) directly to the peripheral injury site at a critical concentration level of mg/L can enhance nerve regeneration and functional recovery through an intriguing epigenetic modulation; (2) folate-releasing NGCs could orchestrate intriguing biochemical-to-biomechanical force transduction to promote neuronal differentiation and regeneration; (3) incorporating FA into POC results in a polymer that enables photoacoustic imaging (PAI) in the tissue trans- parent near-infrared (NIR) window for non-invasive, real-time, in-situ monitoring of nerve scaffold degradation and nerve regeneration. The project’s innovation lie in 1) synthesizing new folate-releasing and photoacoustic citrate biodegradable polymers (POCFA) for nerve scaffold fabrication; 2) elucidating the underexplored gene- specific epigenetic and biochemical-to-biomechanical transduction effects of folate for neuroregeneration; 3) for the first time, exploring the PN regeneration by delivering folate at critical concentrations (mg/L) directly to the injury site; and 4) in vivo real-time dual-modality photoacoustic and ultrasound (PAUS) imaging of nerve scaffold degradation and nerve regeneration. Ultrasound imaging provides underlying anatomical or structural infor- mation of the tissue, whereas spectral photoacoustic imaging (PAI) maps light-absorbing polymers along with vascular structure and associated functional oxygen saturation of the tissue exploiting differential absorption of oxy- and deoxy- hemoglobin’s in the NIR window. The Rigor of Prior Research includes 1) we have previously developed multifunctional multi-channeled biodegradable elastic CUPE NGCs promising for PN regeneration; 2) we have obtained compelling data to support that biologically stable folate displayed intriguing dose-dependent epigenetic and biomechanical effects to promote neuronal differentiation migration and proliferation of both rat Schwann and neuron cells, and the regeneration and functional recovery of 20 mm sciatic nerve defects in rats as early as 4 weeks post-implantation; 3) POCFA displayed unexpected strong absorption in near-infrared-I (NIR-I, 700-1000 nm) and even in NIR-II (1000-1700 nm) window for PAI. The expected outcome of this pro- posal is a practical methodology for the optimal design of imageable NGCs with suitable epigenetic, biomechan- ical, and topographical cues for the regeneration and functional recovery of critically sized nerve defects.

项目总结