A Novel Superparamagnetic Multifunctional Nerve Scaffold: A Remote Actuation Strategy to Boost In Situ Extracellular Vesicles Production for Enhanced Peripheral Nerve Repair

Abstract

Extracellular vesicles (EVs) have inherent advantages over cell‐based therapies in regenerative medicine because their cargos of abundant bioactive cues. Several strategies are proposed to tune EVs production in vitro. However, it remains a challenge for manipulation of EVs production in vivo, which poses significant difficulties for EVs‐based therapies that aim to promote tissue regeneration, particularly for long‐term treatment of diseases like peripheral neuropathy. Herein, a superparamagnetic nanocomposite scaffold capable of controlling EVs production on‐demand is constructed by incorporating polyethyleneglycol/polyethyleneimine modified superparamagnetic nanoparticles into polyacrylamide/hyaluronic acid double‐network hydrogel (Mag‐gel). The Mag‐gel is highly sensitive to rotating magnetic field (RMF), and could act as mechano‐stimulative platform to exert micro/nano‐scale forces on encapsulated Schwann cells (SCs), an essential glial cell in supporting nerve regeneration. By switching the ON/OFF state of RMF, the Mag‐gel could scale up local production of SCs‐derived EVs (SCs‐EVs) both in vitro and in vivo. Further transcriptome sequencing indicated an enrichment of transcripts favorable in axon growth, angiogenesis, and inflammatory regulation of SCs‐EVs in Mag‐gel with RMF, which ultimately results in optimized nerve repair in vivo. Overall, our research provides a noninvasive and remotely time‐scheduled method for fine‐tuning EVs‐based therapies to accelerate tissue regeneration, including that of peripheral nerves.This article is protected by copyright. All rights reserved

Small extracellular vesicles purification and scale-up

“…Melatonin-treated sEVs enhance the regenerative potential of MSCs ( 32 ). In addition, external environments such as magnetic field ( 33 ), flow and stretch ( 34 ), ultrasound ( 35 ), PH ( 36 ), hypoxia ( 37 ), temperature ( 38 ), and light ( 39 ) affect the synthesis and release of sEVs.…”

Dental pulp regeneration strategies: A review of status quo and recent advances

“…3 B) [ 120 ]. The choice of hydrogel type depends on specific application requirements and research objectives, such as injectable hydrogels, microsphere-based hydrogels, bilayer hydrogels, photosensitive hydrogels, magnetic hydrogels, and more [ [121] , [122] , [123] , [124] , [125] [121] , [122] , [123] , [124] , [125] [121] , [122] , [123] , [124] , [125] ]. These hydrogels have the potential to serve as controlled growth factors (GFs) delivery systems and supportive matrices for tissue regeneration, particularly in vascularized soft tissues like the dentin-pulp complex.…”

Therapeutic Potential and Challenges of Mesenchymal Stem Cell-Derived Exosomes for Peripheral Nerve Regeneration: A Systematic Review

“…Research is focusing on new, more effective scaffolds to overcome the burst release of exosomes. One example is a Novel Superparamagnetic Multifunctional Nerve Scaffold with SCs, which explores inducing exosome secretion directly in the patient through a rotating magnetic field that exerts mechanical force on SCs, promoting long-term exosome production [ 85 ]. Research also focuses on preconditioning stem cells—culturally, biochemically, mechanically, or environmentally.…”