Metabolic reprogramming: a new option for the treatment of spinal cord injury

Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they cause.Despite the ongoing development of various therapies for spinal cord injuries,their effectiveness remains unsatisfactory.However,a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming.In this review,we explore the metabolic changes that occur during spinal cord injuries,their consequences,and the therapeutic tools available for metabolic reprogramming.Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling.However,spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism,lipid metabolism,and mitochondrial dysfunction.These metabolic disturbances lead to corresponding pathological changes,including the failure of axonal regeneration,the accumulation of scarring,and the activation of microglia.To rescue spinal cord injury at the metabolic level,potential metabolic reprogramming approaches have emerged,including replenishing metabolic substrates,reconstituting metabolic couplings,and targeting mitochondrial therapies to alter cell fate.The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury.To further advance the metabolic treatment of the spinal cord injury,future efforts should focus on a deeper understanding of neurometabolism,the development of more advanced metabolomics technologies,and the design of highly effective metabolic interventions.

A bioactive injectable self-healing anti-inflammatory hydrogel with ultralong extracellular vesicles release synergistically enhances motor functional recovery of spinal cord injury

The repair and motor functional recovery after spinal cord injury(SCI)remains a worldwide challenge.The inflammatory microenvironment is one of main obstacles on inhibiting the recovery of SCI.Using mesenchymal stem cells(MSCs)derived extracellular vesicles to replace MSCs transplantation and mimic cell paracrine secretions provides a potential strategy for microenvironment regulation.However,the effective preservation and controlled release of extracellular vesicles in the injured spinal cord tissue are still not satisfied.Herein,we fabricated an injectable adhesive anti-inflammatory F127-polycitrate-polyethyleneimine hydrogel(FE)with sustainable and long term extracellular vesicle release(FE@EVs)for improving motor functional recovery after SCI.The orthotopic injection of FE@EVs hydrogel could encapsulate extracellular vesicles on the injured spinal cord,thereby synergistically induce efficient integrated regulation through suppressing fibrotic scar formation,reducing inflammatory reaction,promoting remyelination and axonal regeneration.This study showed that combining extracellular vesicles into bioactive multifunctional hydrogel should have great potential in achieving satisfactory locomotor recovery of central nervous system diseases.

A conductive supramolecular hydrogel creates ideal endogenous niches to promote spinal cord injury repair

The current effective method for treatment of spinal cord injury(SCI)is to reconstruct the biological microenvironment by filling the injured cavity area and increasing neuronal differentiation of neural stem cells(NSCs)to repair SCI.However,the method is characterized by several challenges including irregular wounds,and mechanical and electrical mismatch of the material-tissue interface.In the current study,a unique and facile agarose/gelatin/polypyrrole(Aga/Gel/PPy,AGP3)hydrogel with similar conductivity and modulus as the spinal cord was developed by altering the concentration of Aga and PPy.The gelation occurred through non-covalent interactions,and the physically crosslinked features made the AGP3 hydrogels injectable.In vitro cultures showed that AGP3 hydrogel exhibited excellent biocompatibility,and promoted differentiation of NSCs toward neurons whereas it inhibited over-proliferation of astrocytes.The in vivo implanted AGP3 hydrogel completely covered the tissue defects and reduced injured cavity areas.In vivo studies further showed that the AGP3 hydrogel provided a biocompatible microenvironment for promoting endogenous neurogenesis rather than glial fibrosis formation,resulting in significant functional recovery.RNA sequencing analysis further indicated that AGP3 hydrogel significantly modulated expression of neurogenesis-related genes through intracellular Ca2+signaling cascades.Overall,this supramolecular strategy produces AGP3 hydrogel that can be used as favorable biomaterials for SCI repair by filling the cavity and imitating the physiological properties of the spinal cord.