Search Results (168)

Electroactive biomaterials are a key emerging technology for the treatment of neural damage. Conducting polymer-coated carbon microfibers are particularly useful for this application because they provide directional support for cell growth and tissue repair and simultaneously allow for ultrasensitive recording and stimulation of neural activity. Here, we report in vitro experiments investigating the biology of Schwann cells (SCs), a major player in peripheral nerve regeneration, on electroconducting microfibers. The optimal molecular composition of the cell substrate and cell culture medium was studied for SCs dissociated from rat and pig peripheral nerves. The substrate molecules were then attached to carbon microfibers coated with poly (3,4-ethylenedioxythiophene) doped with poly [(4-styrenesulfonic acid)-co-(maleic acid)] (PCMFs), which served as an electroactive scaffold for culturing nerve explants. Biphasic electrical stimulation (ES) was applied through the microfibers, and its effects on cell proliferation and migration were assessed in different cell culture media. Rodent and porcine SCs avidly migrated on PCMFs functionalized with a complex of poly-L-lysine, heparin, basic fibroblast growth factor, and fibronectin. Serum and forskolin/heregulin increased, by two-fold and four-fold, the number of SCs on PCMFs, respectively, and ES further doubled cell numbers without favoring fibroblast proliferation. ES additionally increased SC migration. These results provide a baseline for using biofunctionalized PCMFs in peripheral nerve repair. Full article

Oxaliplatin-induced peripheral neurotoxicity (OIPN) represents a major challenge in cancer therapy, characterized by dorsal root ganglia (DRG) inflammation and disruption of neuro-glio-vascular unit function. In this study, we investigated the involvement of the scaffold protein IQ Motif Containing GTPase Activating Protein 1 (IQGAP1) and dehydropeptidase-1 (DPEP1) in the DRG response to oxaliplatin (OxPt) and the modulatory effect of cilastatin. Behavioral assessment showed a robust nocifensive response to cold stimuli in OxPt-treated rats, attenuated by cilastatin co-treatment. Our confocal study revealed different cellular and subcellular expression patterns of IQGAP1 and DPEP1 in neurons, glia, and endothelial cells, where both signals overlap approximately one-third. OxPt enhanced cytosolic aggregation of IQGAP1 in neurons and upregulation of signal in glia, accompanied by co-expression of TNFα and IL-6, indicating involvement in the inflammatory process. DPEP1 showed altered subcellular distribution in OxPt-treated animals, suggesting a potential role in the inflammatory cascade. Notably, IQGAP1 expression was diminished in endothelial membranes under OxPt, while cilastatin preserved endothelial IQGAP1-CD31 colocalization, suggesting partial restoration of blood-nerve barrier integrity. These findings identify IQGAP1 and DPEP1 as key players in DRG inflammation and position cilastatin as a promising modulator of OIPN through neuro-glio-vascular stabilization. Full article

Spinal cord injury (SCI) remains a devastating neurological condition characterized by loss of sensory, motor and autonomic function. Despite decades of research, no FDA-approved regenerative therapies currently exist to restore lost function following SCI. Schwann cells (SCs) support axon regeneration, remyelination, and neuroprotection after SCI, with their therapeutic potential validated in clinical trials demonstrating safe and feasible transplantation in humans. Although SC transplantation has shown promising results, challenges remain, including modest graft survival, limited host integration, and restricted migration that collectively contribute to constrain efficacy. To address these limitations, biomaterial scaffolds have been explored as synergistic platforms to enhance SC delivery and function. When combined with natural or synthetic biomaterials such as hydrogels, nanofiber scaffolds, or ECM-mimetic matrices, SCs demonstrate improved survival, retention, spatial distribution, and regenerative activity. The intrinsic regenerative properties of SCs, first demonstrated in models of peripheral nerve injury, make them particularly well-suited for neural repair of the central nervous system (CNS) compared to other cell types and their effectiveness can be enhanced synergistically when combined with biomaterials. These constructs not only provide structural support but also modulate the lesion microenvironment, enhance axon growth and improve SC integration with host tissue. Combinatorial approaches incorporating biomaterials with SCs are emerging as next-generation strategies to optimize repair for clinical translation. This review focuses on current progress in SC-based therapies combined with biomaterials, highlighting key preclinical advances, clinical translation efforts, and the path forward toward effective regenerative interventions for SCI. Full article

Bioactive materials have recently shown potential in nerve repair and regeneration by promoting the growth of new cells, tissue repair, and restoring nerve function. These natural, synthetic, and hybrid materials offer a biomimetic structure, enhance cell attachment, and release bioactive molecules that promote the axonal extension of severed nerves. Scaffold-based preclinical studies have shown promising results on enhancing nerve repair; however, they are limited by the immune response and fabrication, scalability, and cost. Nevertheless, advances in manufacturing, including 3D bioprinting, and other strategies, such as gene editing by CRISPR, will overcome these shortcomings. The opportunity for the development of individualized approaches and specific treatment plans for each patient will also increase the effectiveness of bioactive materials for the treatment of nerve injuries. Combining bioactive materials with the neural interface can develop new reliable therapeutic solutions, particularly for neuroprosthetics. Finally, it is essential to stress a multidisciplinary focus, and future studies are needed to enhance the potential of bioactive materials for patients with nerve injuries and the field of regenerative medicine. Full article

Neuropathic pain is a persistent and exhausting condition which results from damage to the nervous system and is often accompanied by emotional and cognitive impairments. In this study, we investigated dynamic changes in pain-related behaviors over 8 weeks using a spared nerve injury (SNI) model in male C57Bl/6 mice. We examined behavioral outcomes in conjunction with glial activation, neurogenesis, and glutamatergic signaling in the hippocampus to elucidate the mechanisms underlying cognitive and affective alterations associated with chronic pain. Our findings demonstrate that SNI-induced neuropathic pain progressively increases anxiety-like behavior and impairs both working and long-term memory. These behavioral deficits are accompanied by significant activation of microglia and astrocytes, a reduction in hippocampal neurogenesis, and a decrease in the expression of NMDA and AMPA glutamate receptor subunits and the scaffolding protein PSD-95. Taken together, our results suggest that hippocampal neuroinflammation and associated synaptic dysfunction contribute to the affective and cognitive disturbances observed in chronic pain, providing insight into potential molecular targets for therapeutic intervention. Full article

This review is different from previous studies focusing on polypyrrole (PPy) in universal fields such as sensors and supercapacitors. It is the first TO systematically review the specific applications of PPy-based electrospun nanofiber composites in the biomedical field, focusing on its biocompatibility regulation mechanism and tissue repair function. Although PPy exhibits exceptional electrical conductivity, redox activity, and biocompatibility, its clinical translation is hindered by processing challenges and poor degradability. These limitations can be significantly mitigated through composite strategies with degradable nanomaterials, enhancing both process compatibility and biofunctionality. Leveraging the morphological similarity between electrospun nanofibers and the natural extracellular matrix (ECM), this work comprehensively analyzes the topological characteristics of three composite fiber architectures—randomly distributed, aligned, and core–shell structures—and elucidates their application mechanisms in nerve regeneration, skin repair, bone mineralization, and myocardial tissue reconstruction (e.g., facilitating oriented cell migration and regulating differentiation through specific signaling pathway activation). The study further highlights critical challenges in the field, including PPy’s poor solubility, limited spinnability, insufficient mechanical strength, and scalability limitations. Future efforts should prioritize the development of multifunctional gradient composites, intelligent dynamic-responsive scaffolds, and standardized biosafety evaluation systems to accelerate the substantive translation of these materials into clinical applications. Full article

Peripheral myelination is driven by the intricate interplay between Schwann cells and axons, coordinated through molecular signaling and the structural organization of their shared environment. While the biochemical regulation of this process has been extensively studied, the influence of spatial architecture and mechanical cues remains poorly understood. Here, we use in vitro co-culture models—featuring microfluidic devices and hydrogel-based scaffolds—to explore how extracellular organization, cellular density, and spatial constraints shape Schwann cell behavior. Our results show that (i) pro-myelinating effects triggered by ascorbic acid administration is distally propagated along axons in Schwann cell-DRG co-cultures, (ii) ascorbic acid modulates Neuregulin-1 expression, (iii) a critical threshold of cellular density is required to support proper Schwann cell differentiation and myelin formation, and (iv) spatial confinement promotes myelination in the absence of ascorbic acid. Together, these findings highlight how spatial and structural parameters regulate the cellular and molecular events underlying peripheral myelination, offering new physiologically relevant models of myelination and opening new avenues for peripheral nerve repair strategies. Full article

Peripheral nerve injuries (PNIs) commonly result from trauma, compression, or iatrogenic causes, leading to functional deficits. Despite the peripheral nervous system’s regenerative capacity, current treatments yield inconsistent outcomes. Basic science and translational research supporting nerve repair remain underdeveloped, partly due to the absence of standardized protocols, limiting reproducibility. Animal models are essential for studying injury mechanisms, repair strategies, and therapeutic development. This review examines commonly used animal models in PNI research, from non-mammalian species to rodents and large mammals. We discuss the relevance of injury types, experimental variables (i.e., age, sex, nerve type), and study design elements (i.e., nerve gap size, injury induction methods). Assessing these models’ strengths and limitations, this review aims to guide researchers in selecting appropriate models that enhance preclinical relevance. It also addresses the need for standardized protocols and future directions for improving PNI research and patient outcomes. Various PNI treatments—including microsurgery, nerve grafts, scaffolds, stem cells, immunomodulators, nerve augmentation strategies, and polyethylene glycol-mediated fusion—have been developed using animal models. These models are essential for driving innovation and translating emerging therapies to improve outcomes across a broad range of peripheral nerve injuries. Full article

Background/Objectives: Previous work in our lab demonstrated that a 3D scaffold containing lysine-modified chitosan (K-chitosan) and decorated with Matrilin-2 (MATN2) enhanced Schwann cell (SC) migration and axonal outgrowth in vitro and ex vivo. This study aimed to assess the regenerative effect of this scaffold compared to that of a collagen conduit and an autograft using a segmental rat sciatic nerve injury model. Methods: A total of 30 Lewis Rats were assigned into three groups: an untreated collagen conduit (UC) group, a collagen conduit treated with MATN2 K-chitosan (TC) group, and a reverse autograft (RA) group. Walking force measurements, compound muscle action potential (CMAP), the wet muscle weight of the tibialis anterior and the gastrocnemius, and axonal histomorphometry were assessed. Results: The walking force and CMAP were significantly higher in the TC group compared to those in the UC group, with no significant difference between the TC and RA groups. The muscle weights were significantly greater in the TC group compared to those in the UC group but smaller than those in the RA group. The TC group experienced significantly greater axonal regeneration compared to that with the UC, and no differences were found with the RA. The TC group further demonstrated significantly greater cell counts than those in the UC group and greater affinity of the Schwann cells towards nerve reconstruction. Conclusion: The MATN2 K-chitosan scaffold significantly improved nerve regeneration and was comparable to the RA, supporting the development of a novel bio-conductive scaffold conduit. Full article

Tissue engineering techniques aim to improve or replace biological tissues or organs by utilizing the extracellular matrix to facilitate the repair of damaged tissues or organs. Collagen-based scaffolds offer numerous advantages, including excellent biocompatibility, low immunogenicity, biodegradability, hemostatic properties, and mechanical strength. Collagen scaffolds can reconstruct the extracellular microenvironment, promote cell adhesion, migration, proliferation, and differentiation, and play a critical role in cell-to-cell and cell-to-matrix interactions. Collagen has been extensively utilized in tissue engineering to facilitate tissue repair and organ reconstruction. This review examines the properties of collagen, including its composition, structure, biological characteristics, and role in regulating various cellular behaviors. Additionally, the preparation of cell-loaded collagen scaffolds is discussed, along with a comprehensive overview of their applications in various tissues, including skin, nerve, bone/cartilage, heart, liver, and others. Emerging strategies and future perspectives for clinical tissue repair are also presented. This review provides a comprehensive synthesis of the mechanisms underlying the use of cell-loaded collagen scaffolds as advanced biomaterials, emphasizing their potential to expand the clinical applications of collagen. Full article

Peripheral nerve injuries (PNIs) pose significant challenges to recovery, often resulting in impaired function and quality of life. To address these challenges, nerve guidance conduits (NGCs) are being developed as effective strategies to promote nerve regeneration by providing a supportive framework that guides axonal growth and facilitates reconnection of severed nerves. Among the materials being explored, graphene-based materials (GBMs) have emerged as promising candidates due to their unique properties. Their unique properties—such as high mechanical strength, excellent electrical conductivity, and favorable biocompatibility—make them ideal for applications in nerve repair. The integration of 3D printing technologies further enhances the development of GBM-based NGCs, enabling the creation of scaffolds with complex architectures and precise topographical cues that closely mimic the natural neural environment. This customization significantly increases the potential for successful nerve repair. This review offers a comprehensive overview of properties of GBMs, the principles of 3D printing, and key design strategies for 3D-printed NGCs. Additionally, it discusses future perspectives and research directions that could advance the application of 3D-printed GBMs in nerve regeneration therapies. Full article

Melatonin, a natural hormone with antioxidant, anti-inflammatory, and regenerative properties, has gained increasing attention in tissue engineering for its ability to enhance the therapeutic potential of biopolymeric scaffolds. These scaffolds, designed to mimic the extracellular matrix, provide structural support and a bioactive environment for tissue regeneration. By integrating melatonin, researchers aim to create multifunctional scaffolds that promote cell proliferation, modulate inflammatory responses, and improve wound healing outcomes. Challenges in utilizing melatonin include maintaining its stability under light, heat, and oxygen exposure, and optimizing its release profile for sustained therapeutic effects. Innovative fabrication methods, such as electrospinning, 3D printing, and lyophilization, have enabled precise control over scaffold architecture and melatonin delivery. These techniques ensure enhanced interactions with target tissues and tailored regeneration processes. Combining melatonin with growth factors, cytokines, and antimicrobial agents offers the potential for multifunctional applications, from chronic wound management to bone and nerve regeneration. Continued research in this field promises transformative solutions in regenerative medicine, expanding the clinical applicability of melatonin-enriched scaffolds. This review highlights the current progress, challenges, and opportunities associated with harnessing melatonin’s therapeutic potential within tissue engineering frameworks. Full article

Peripheral nerve injuries are common complications in surgical and dental practices, often resulting in functional deficiencies and reduced quality of life. Current treatment choices, such as autografts, have limitations, including donor site morbidity and suboptimal outcomes. Adipose-derived stem cells (ADSCs) have shown assuring regenerative potential due to their accessibility, ease of harvesting and propagation, and multipotent properties. This review investigates the therapeutic potential of ADSCs in peripheral nerve regeneration, focusing on their use in bioengineered nerve conduits and supportive microenvironments. The analysis is constructed on published case reports, organized reviews, and clinical trials from Phase I to Phase III that investigate ADSCs in managing nerve injuries, emphasizing both peripheral and orofacial applications. The findings highlight the advantages of ADSCs in promoting nerve regeneration, including their secretion of angiogenic and neurotrophic factors, support for cellular persistence, and supplementing scaffold-based tissue repair. The regenerative capabilities of ADSCs in peripheral nerve injuries offer a novel approach to augmenting nerve repair and functional recovery. The accessibility of adipose tissue and the minimally invasive nature of ADSC harvesting further encourage its prospective application as an autologous cell source in regenerative medicine. Future research is needed to ascertain standardized protocols and optimize clinical outcomes, paving the way for ADSCs to become a mainstay in nerve regeneration. Full article

Background: Pain is a complex condition influenced by peripheral, central, immune, and psychological factors. Multitarget approaches offer a more effective and safer alternative to single-target analgesics by enhancing efficacy, reducing side effects, and minimizing tolerance. This study aimed to identify a novel multitarget analgesic with improved pharmacological properties. Methods: An in vivo-guided screening approach was used to discover a new analgesic compound. Compound 29, derived from a novel scaffold inspired by opiranserin and vilazodone pharmacophores, was identified through analog screening in the formalin test. Its efficacy was further evaluated in the spinal nerve ligation (SNL) model of neuropathic pain. Mechanistic studies explored its interaction with neurotransmitter transporters and receptors, while pharmacokinetic and safety assessments were conducted to determine its stability, brain penetration, and potential toxicity. Results: Compound 29 demonstrated high potency in the formalin test, with an ED50 of 0.78 mg/kg in the second phase and a concentration-dependent effect in the first phase. In the SNL model, it produced dose-dependent analgesic effects, increasing withdrawal thresholds by 24% and 45% maximum possible effect (MPE) at 50 and 100 mg/kg, respectively. Mechanistic studies revealed strong triple uptake inhibition, particularly at dopamine (DAT) and serotonin (SERT) transporters, alongside high-affinity 5-HT2A receptor antagonism. Pharmacokinetic analysis indicated enhanced stability and blood–brain barrier permeability. In vitro studies confirmed its nontoxicity to HT-22 cells but revealed potential hERG inhibition and strong CYP3A4 inhibition. Conclusions: Compound 29 is a promising multitarget analgesic with potent efficacy and favorable pharmacokinetics. Ongoing optimization efforts aim to mitigate side effects and enhance its therapeutic profile for clinical application. Full article

Background: The combination of macroporous cryogels with synthetic peptide factors represents a promising but poorly explored strategy for the development of extracellular matrix (ECM)-mimicking scaffolds for peripheral nerve (PN) repair. Methods: In this study, IKVAV peptide was functionalized with terminal lysine residues to allow its in situ cross-linking with gelatin macromer, resulting in the formation of IKVAV-containing proteinaceous cryogels. The controllable inclusion and distribution of the peptide molecules within the scaffold was verified using a fluorescently labelled peptide counterpart. The optimized cryogel scaffold was combined with polycaprolactone (PCL)-based shell tube to form a suturable nerve conduit (NC) to be implanted into sciatic nerve diastasis in rats. Results: The NC constituents did not impair the viability of primary skin fibroblasts. Concentration-dependent effects of the peptide component on interrelated viscoelastic and swelling properties of the cryogels as well as on proliferation and morphological differentiation of neurogenic PC-12 cells were established, also indicating the existence of an optimal-density range of the introduced peptide. The in vivo implanted NC sustained the connection of the nerve stumps with partial degradation of the PCL tube over eight weeks, whereas the core-filling cryogel profoundly improved local electromyographic recovery and morphological repair of the nerve tissues, confirming the regenerative activity of the developed scaffold. Conclusions: These results provide proof-of-concept for the development of a newly designed PN conduit prototype based on IKVAV-activated cryogel, and they can be exploited to create other ECM-mimicking scaffolds. Full article