Central and peripheral nerve injuries can lead to permanent paralysis and organ dysfunction. In recent years, many cell and exosome implantation techniques have been developed in an attempt to restore function after nerve injury with promising but generally unsatisfactory clinical results. Clinical outcome may be enhanced by bio-scaffolds specifically fabricated to provide the appropriate three-dimensional (3D) conduit, growth-permissive substrate, and trophic factor support required for cell survival and regeneration. In rodents, these scaffolds have been shown to promote axonal regrowth and restore limb motor function following experimental spinal cord or sciatic nerve injury. Combining the appropriate cell/exosome and scaffold type may thus achieve tissue repair and regeneration with safety and efficacy sufficient for routine clinical application. In this review, we describe the efficacies of bio-scaffolds composed of various natural polysaccharides (alginate, chitin, chitosan, and hyaluronic acid), protein polymers (gelatin, collagen, silk fibroin, fibrin, and keratin), and self-assembling peptides for repair of nerve injury. In addition, we review the capacities of these constructs for supporting in vitro cell-adhesion, mechano-transduction, proliferation, and differentiation as well as the in vivo properties critical for a successful clinical outcome, including controlled degradation and re-absorption. Finally, we describe recent advances in 3D bio-printing for nerve regeneration.

Purpose: Nerve injury-induced pain is difficult to treat. In this study, we developed an alginate scaffold with human umbilical cord mesenchymal stem cell exosomes (EX-SC) to treat nerve injury-induced pain. Materials and Methods: The scaffold was prepared and characterized for its physical traits and biocompatibility. In vitro studies of PC12 and HEK293 cells were used to evaluate the neuroprotective and neurotrophic effects of exosomes. Right L5/6 spinal nerve ligation (SNL) was performed in Sprague-Dawley rats to induce mechanical allodynia and thermal hyperalgesia, evaluated by von Frey hair and radiant heat tests. The EX-SC was wrapped around ligated L5/6 spinal nerves for treatment. Western blotting and immunofluorescence staining were used to evaluate neuron/glial activation, cytokines and neurotrophic factor of affected dorsal root ganglion (DRG). Results: In cell culture assay, the exosomes induce neurite outgrowth of PC12 cells and protect PC12 and HEK293 cells against formaldehyde acid treatment. On post-ligation day 21, rats receiving EX-SC had significantly higher median (interquartile range) withdrawal threshold and latency [14.1 (13.7– 15.5) g, 14.2 (13.7– 15.3) s] than saline-SC-treated rats [2.1 (1.7– 3.0) g, 2.0 (1.8– 2.4) s, P=0.02 and 0.002]. The EX-SC also attenuated SNL-induced up-regulation of c-Fos, GFAP, Iba1, TNF-α and IL-1β, while enhancing the level of IL-10 and GDNF, in the ipsilateral L5/6 DRG. After implantation for 21 days, the EX-SC enhanced the expression of myelin basic protein and IL-10 in injured L5/6 axons. Conclusion: We demonstrate the EX-SC possesses antinociceptive, anti-inflammation and pro-neurotrophic effects in the SNL pain model. It could be a promising therapeutic alternative for nerve injury-induced pain.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising therapeutic strategy for spinal cord injury (SCI). These nanosized vesicles possess unique properties such as low immunogenicity and the ability to cross biological barriers, making them ideal carriers for delivering bioactive molecules to injured tissues. MSC-EVs have been demonstrated to exert multiple beneficial effects in SCI, including reducing inflammation, promoting neuroprotection, and enhancing axonal regeneration. Recent studies have delved into the molecular mechanisms underlying MSC-EV-mediated therapeutic effects. Exosomal microRNAs (miRNAs) have been identified as key regulators of various cellular processes involved in SCI pathogenesis and repair. These miRNAs can influence inflammation, oxidative stress, and apoptosis by modulating gene expression. This review summarized the current state of MSC-EV-based therapies for SCI, highlighting the underlying mechanisms and potential clinical applications. We discussed the challenges and limitations of translating these therapies into clinical practice, such as inconsistent EV production, complex cargo composition, and the need for targeted delivery strategies. Future research should focus on optimizing EV production and characterization, identifying key therapeutic miRNAs, and developing innovative delivery systems to maximize the therapeutic potential of MSC-EVs in SCI.

The pathogenesis of ketamine cystitis (KC) has been recently linked with immune response to patients but the same has not yet been established. Hence, this study aims to propose a possible immune mechanism of irreversible bladder damage caused by KC. A total of 53 KC patients and 21 healthy volunteers as controls have been retrospectively assessed. The levels of serum immunoglobulin E (IgE), IL-6, and IFN-γ of KC patients were significantly higher than those of controls, whereas the TGF-β levels of KC patients substantially reduced but the IL-2 and IL-4 levels of KC patients were comparable to those of controls. Moreover, the KC patients had significantly higher counts of TH1, TH2, and TH17 cells than those of controls. The immune response of KC users may begin with the IL-6 production and differentiation of TH17 and may be followed by alternating between high expressions of TH1 and TH2. The IL-6 may further suppress the TREG cells which can aggravate chronic inflammation in KC patients and the imbalance in TH17 and TREG cells may involve the pathogenesis of KC. Further investigation is needed to define the role of IL-6 in TH1/TH2/TH17-regulated signaling pathway in ketamine-induced cystitis.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising therapeutic strategy for spinal cord injury (SCI). These nanosized vesicles possess unique properties such as low immunogenicity and the ability to cross biological barriers, making them ideal carriers for delivering bioactive molecules to injured tissues. MSC-EVs have been demonstrated to exert multiple beneficial effects in SCI, including reducing inflammation, promoting neuroprotection, and enhancing axonal regeneration. Recent studies have delved into the molecular mechanisms underlying MSC-EV-mediated therapeutic effects. Exosomal microRNAs (miRNAs) have been identified as key regulators of various cellular processes involved in SCI pathogenesis and repair. These miRNAs can influence inflammation, oxidative stress, and apoptosis by modulating gene expression. This review summarizes the current state of MSC-EV-based therapies for SCI, highlighting the underlying mechanisms and potential clinical applications. We discuss the challenges and limitations of translating these therapies into clinical practice, such as inconsistent EV production, complex cargo composition, and the need for targeted delivery strategies. Future research should focus on optimizing EV production and characterization, identifying key therapeutic miRNAs, and developing innovative delivery systems to maximize the therapeutic potential of MSC-EVs in SCI.

Spinal cord injury (SCI) is a devastating neurological condition characterized by irreversible primary damage followed by a complex secondary injury cascade involving oxidative stress, neuroinflammation, iron dysregulation, and regulated cell death. Among these mechanisms, ferroptosis, a distinct, iron-dependent form of regulated cell death driven by lipid peroxidation and redox imbalance, is increasingly recognized as a critical mediator of neurodegeneration after SCI. The miRNAs play essential roles in neural injury responses by modulating inflammation, oxidative stress, and cell-death pathways. Growing evidence indicates that miRNAs closely regulate ferroptosis-related signaling networks following SCI, influencing key molecular targets including iron metabolism, antioxidant defense systems, and lipid peroxidation pathways. Conversely, ferroptotic stress may alter miRNA expression profiles, suggesting a bidirectional regulatory relationship. In addition, ferritinophagy, a selective autophagy pathway degrading ferritin via nuclear receptor coactivator 4 (NCOA4), has emerged as an important yet underexplored regulator of intracellular iron homeostasis and ferroptosis susceptibility in SCI. This review systematically summarizes current evidence on the molecular mechanisms linking miRNAs and ferroptosis in SCI, highlights how miRNA-mediated regulation of ferroptosis contributes to neuronal death, glial responses, and impaired regeneration, and discusses emerging therapeutic strategies targeting this axis to promote neuroprotection and functional recovery. By integrating recent experimental findings, we aim to provide mechanistic insight and identify translational opportunities for miRNA- and ferroptosis-based interventions in SCI.