Search Results (817)

The small heat shock protein HSPB1 is a ubiquitously expressed mechanoresponsive chaperone essential for cytoskeletal remodeling under mechanical load. Mutations in HSPB1, including S135F, cause Charcot-Marie-Tooth (CMT) peripheral neuropathy, yet the mechanisms underlying the selective vulnerability of peripheral nerves remain enigmatic. Here we demonstrate that substrate stiffness is a critical determinant of HSPB1^S135F-mediated neurodegeneration. Using stiffness-tunable polydimethylsiloxane (PDMS) substrates (1 kPa, 10 kPa, 2 MPa) and uniaxial cyclic stretch, we show that primary dorsal root ganglia (DRG) neurons and SH-SY5Y cells expressing HSPB1^S135F exhibit profound deficits in mechanoadaptation. On compliant substrates (10 kPa), HSPB1^S135F causes stretch-induced axon fragmentation and neuronal death, whereas HSPB1^WT confers robust neuroprotection. HSPB1^S135F also disrupts stiffness-directed neuritogenesis in differentiated SH-SY5Y cells: HSPB1^WT-expressing cells show optimal axonal outgrowth and βIII-tubulin expression on 10 kPa substrates mimicking muscle tissue stiffness, while HSPB1^S135F mutants display disorganized focal adhesions and complete differentiation failure. Mechanistically, we uncover that HSPB1^S135F dysregulates stage-specific transglutaminase (TGase) expression—insufficient TGase during early neuritogenesis impairs filopodia stabilization, whereas aberrant TGase persistence at late stages constrains axon extension. Our findings establish HSPB1 as a biomechanical sensor that integrates ECM stiffness signals to coordinate peripheral nerve regeneration, and identify defective mechanoadaptation as a previously unrecognized pathomechanism in CMT. These results open new avenues for stiffness-targeted therapeutic strategies in peripheral neuropathy. Full article

Background/Objectives: With the biphasic of cataract onset age, presenile cataract (40–55 years) and age-related cataract (≥70 years) demonstrate notable differences in perioperative dry eye manifestations. This review aims to systematically compare their differential characteristics, mechanisms, and management strategies. Methods: An indirect evidence synthesis was conducted, encompassing 71 clinical and mechanistic studies evaluating perioperative dry eye in these two patient populations. Results: Presenile patients predominantly present with evaporative dry eye secondary to meibomian gland dysfunction (55–70%), persisting for 3–6 months postoperatively, especially in subgroups with metabolic disorders, female sex, diabetes with rosacea, or preoperative anxiety. In contrast, age-related patients primarily exhibit mixed-type dry eye, with a shorter recovery period (1–3 months), characterized by corneal nerve demyelination and meibomian gland fibrosis. Mechanistically, the presenile group is associated with glandular functional overload, acute inflammation, and exogenous oxidative stress, while the age-related group shows degenerative degenerative atrophy, chronic low-grade inflammation (senescence-associated secretory phenotype, SASP), and impaired nerve regeneration. Conclusions: Perioperative dry eye exhibits inherent differences between presenile and age-related cataract patients, requiring age-stratified and subgroup-targeted management strategies for precise ocular surface care. However, due to the absence of direct head-to-head studies, these findings are derived from indirect evidence and should be considered hypothesis-generating. Full article

Background and Objectives: Bell’s palsy (BP) is the most common cause of acute unilateral peripheral facial nerve paralysis. The aim of this study was to evaluate the time to complete clinical recovery in patients with BP treated with acupuncture and to identify baseline clinical and electrophysiological predictors of recovery outcomes. In addition, electrophysiological characteristics at the time of complete clinical recovery were examined. Materials and Methods: This prospective, observational, uncontrolled cohort study included 1050 patients with clinically confirmed BP who received acupuncture as the only therapeutic intervention between January 2017 and August 2025. Clinical severity was assessed using the House–Brackmann (HB) and Sunnybrook (SB) grading systems. Electrophysiological evaluation included compound muscle action potential (CMAP) analysis and needle electromyography (EMG). Time-to-event analysis was performed using the Kaplan–Meier method and Cox proportional hazards regression analysis. Results: Complete clinical recovery was achieved in 843 patients (80.3%). The median time to recovery was 40 days (IQR 30–60). Patients with milder baseline deficits (HB II–IV) demonstrated significantly faster recovery than those with severe paralysis (HB V–VI) (log-rank p < 0.001). In multivariable Cox regression analysis, higher baseline HB grade, older age, and more severe EMG denervation were independently associated with slower recovery. Residual electrophysiological abnormalities persisted in most patients despite complete clinical recovery. Conclusions: Recovery from BP is a dynamic and heterogeneous process, significantly influenced by initial clinical severity and the degree of electrophysiological impairment. Combined clinical and electrophysiological assessment may contribute to more precise prognostic stratification and follow-up of patients with BP. Persistent electrophysiological abnormalities despite complete clinical recovery suggest that complete clinical recovery may precede complete neurophysiological regeneration of the facial nerve. Full article

Spinal cord injury (SCI) is a devastating central nervous system disorder that causes irreversible loss of sensory and motor functions below the lesion, seriously compromising patients’ daily activities and quality of life. Due to the inherent shortcomings of existing therapeutic strategies and the rapid progress of material engineering, developing advanced functional materials has emerged as a promising approach for SCI treatment. This review comprehensively summarizes the applications of polymeric materials, inorganic materials, bioactive materials, and composite biomaterials for SCI treatment and regeneration, with a focus on their underlying mechanisms, therapeutic performance, and research trends. Cumulative evidence indicates that these materials possess versatile biological functions and great application potential in facilitating nerve regeneration and tissue reconstruction after SCI. In short, in-depth understanding of material-based therapeutic systems can offer innovative references for the optimization of SCI treatment regimens. Nevertheless, more preclinical and translational investigations are still indispensable to accelerate their clinical transformation and widespread practical use. Full article

Background and Clinical Significanc: Neuropathic corneal pain is a debilitating condition characterized by ocular pain disproportionate to clinical signs, often resulting from peripheral and central sensitization of the corneal somatosensory pathway. Emerging evidence suggests that chronic involuntary muscle contraction in blepharospasm may lead to irritation of trigeminal afferents and corneal neurogenic inflammation, potentially predisposing patients to neuropathic corneal pain. Given its debilitating nature, early recognition can prevent the progression of neuropathic sequelae. This study examines the potential role of blepharospasm as a predisposing factor contributing to neuropathic corneal pain. Case Presentation: This retrospective case series describes three cases (median age: 50 years) of neuropathic corneal pain in association with blepharospasm and their clinical course following multimodal treatment over a median follow-up period of one year. Ocular surface was evaluated using slit-lamp biomicroscopy, while corneal nerve structure and morphology were assessed with in vivo confocal microscopy. All the three subjects presented with minimal ocular surface staining but disproportionate ocular pain characterized by burning sensation and photophobia. Proparacaine challenge testing was performed to determine the subtype of neuropathic corneal pain. Pain symptoms and quality of life were evaluated using the Ocular Pain Assessment Survey and Ocular Surface Disease Index questionnaires. In vivo confocal microscopy demonstrated characteristic corneal nerve abnormalities including reduced corneal nerve density, increased nerve tortuosity, and the presence of microneuromas. Treatment included oral Pregabalin or Gabapentin, topical lubricants, Cyclosporine 0.05% (1 case), and 20% autologous serum eye drops (1 case). Two of the three cases received four to five injections of botulinum toxin for blepharospasm, whereas one had undergone a single injection prior to review. All patients also received weekly periorbital quantum molecular resonance electrotherapy for two months. Improvements were observed across multiple domains of the Ocular Pain Assessment Survey and Ocular Surface Disease Index evaluation, including ocular pain, photophobia, non-ocular pain, and quality-of-life measures following multimodal treatment. The co-existence of blepharospasm and neuropathic corneal pain observed in our cases supports a possible association between chronic periocular muscle hyperactivity and corneal nociceptor sensitization. Proposed mechanisms include chronic trigeminal nerve irritation, neurogenic inflammation, and sensitization mediated by pro-inflammatory neuropeptides. Multimodal treatment targeting both motor hyperactivity and neuropathic pain pathways appeared to provide symptomatic relief, including the use of quantum molecular resonance electrotherapy, which might modulate pain pathways, block nociceptor neurotransmission, and accelerate corneal nerve regeneration. Given the complexity of the neural pathways responsible for ocular discomfort, further studies are required to elucidate the relationship between neuropathic corneal pain and blepharospasm in larger cohorts, as well as refine existing therapeutic approaches, including evaluating the therapeutic role of electrotherapy. Conclusions: Blepharospasm may represent a potential predisposing factor of neuropathic corneal pain. Early recognition and concurrent treatment of blepharospasm and neuropathic corneal pain can effectively relieve symptoms and improve quality of life. Adopting a multimodal treatment approach is therefore recommended. Full article

Endometriosis is a long-term gynecological condition marked by the growth of endometrial-like tissue outside the uterus, which undergoes proliferation, bleeding, and regeneration. This disease is associated with disrupted steroid hormone signaling, notably progesterone (P4) resistance and estradiol (E2) dominance. P4 resistance has been associated with impaired activation of the progesterone receptor (PR) and reduced transcription of P4 target genes, while elevated E2 levels induce estrogen receptor (ER)-mediated signaling, enhancing estrogen-dependent lesion growth. This hormonal imbalance contributes to a pro-inflammatory microenvironment, chronic pelvic pain, infertility, and enhanced neuroangiogenesis. Emerging evidence indicates that the coordinated regulation of neurotrophins and sex hormones promotes nerve fibers and blood vessel growth and invasion within endometriotic lesions. P4 and E2 have been shown to modulate the expression of key neurotrophins, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). This review presents current evidence on the interplay between neurotrophins and ovarian steroids in endometriosis, with a specific focus on their contribution to neuroangiogenesis and pain pathophysiology. The review includes articles in English containing the Medical Subject Headings (MeSH) terms: “endometriosis”, “neurotrophins”, “nerve growth factor”, “brain-derived neurotrophic factor”, “neuroangiogenesis”, “progesterone”, and “estradiol”, found in the PubMed database published between 2000 and 24 May 2026. This review included a range of original research articles, systematic reviews, meta-analyses, prospective observational studies, case–control studies, and review papers, for a total of 122 articles. Full article

Background and Objectives: Conventional supramalleolar osteotomy (SMO) often involves a concomitant fibular osteotomy (FO), which carries risks, such as nonunion and nerve injury. We evaluated the clinical and radiological outcomes of a fibula-preserving SMO (FP-SMO) combined with arthroscopic modified Broström operation (MBO) in patients with medial compartment varus ankle osteoarthritis and chronic lateral ankle instability. Materials and methods: We retrospectively reviewed 22 patients who underwent medial opening wedge FP-SMO and arthroscopic MBO between 2014 and 2019. Clinical outcomes were assessed using the Visual Analog Scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot score, and Foot and Ankle Outcome Score (FAOS). Radiological evaluation included the anterior drawer test (ADT), talar tilt angle, tibiotalar surface (TTS) angle, medial distal tibial angle (MDTA), tibial lateral surface (TLS) angle, Takakura stage, and International Cartilage Regeneration and Joint Preservation Society (ICRS) grade assessed during second-look arthroscopy. Results: At a mean follow-up of 17.22 months, the mean VAS, AOFAS, and FAOS scores improved significantly (p< 0.001). Radiologically, the mean ADT decreased from 5.98 mm to 4.70 mm (p = 0.015), and the mean talar tilt angle decreased from 9.85° to 6.09° (p< 0.001). The mean TTS angle increased from 80.46° to 84.86° (p = 0.021), and the mean MDTA increased from 85.03° to 91.26° (p< 0.001). The TLS angle showed no significant change from 81.17° to 81.54° (p = 0.238). Takakura stage and ICRS grade improved or remained stable in all patients. No major complications, including nonunion, were observed. Conclusions: FP-SMO combined with arthroscopic MBO demonstrated favorable short-term clinical and radiological outcomes in selected patients with medial compartment varus ankle osteoarthritis and chronic lateral ankle instability. This combined approach may be a feasible joint-preserving option that addresses coronal malalignment and lateral ankle instability without requiring FO; however, longer-term comparative studies are needed to confirm its durability and clinical utility. Full article

Background: Meralgia paresthetica (MP) of the lateral femoral cutaneous is a rare, nerve-entrapment condition, often related to an inflammatory and fibrotic pathological component. Although most cases resolve with conservative management, refractory presentations may require interventional or surgical treatment. Platelet-rich plasma (PRP) has demonstrated emerging potential in peripheral neuropathies through anti-inflammatory, neurotrophic, and antifibrotic mechanisms. Case Presentation: We report the case of a 64-year-old professional scuba diving instructor with occupational MP related to repetitive compression from a tight lead weight belt. Symptoms persisted for six months despite conservative therapies. Clinical examination supported lateral femoral cutaneous nerve (LFCN) entrapment. The patient underwent three serial perineural PRP injections prepared from autologous blood and administered along the inguinal course of the nerve. Progressive symptom reduction was observed after each session, reaching approximately 90% improvement at two months. At six months, the patient was pain-free and had returned to full professional activity without limitations. Discussion: Occupational microcompression may induce intraneural edema, ischemia, and perineural fibrosis, creating a biological substrate amenable to regenerative intervention. PRP delivers concentrated growth factors capable of promoting axonal regeneration, angiogenesis, and modulation of the neuroinflammatory microenvironment. Preclinical and clinical evidence in other compressive neuropathies supports this translational rationale. Conclusions: Perineural PRP infiltration may represent a safe and promising regenerative strategy for refractory occupational MP. Controlled clinical studies are needed to define optimal protocols, patient selection criteria, and long-term efficacy in peripheral compressive neuropathies. Full article

Vascular–osteogenic coupling plays a central regulatory role in bone regeneration, but it is frequently impaired under pathological conditions, including aging, ischemia, and chronic inflammation, which compromises efficient bone repair. Gelatin methacryloyl (GelMA) hydrogels, which combine extracellular matrix-like bioactivity, adjustable mechanical properties, and compatibility with three-dimensional biomanufacturing, have become a widely used material platform for vascularized bone regeneration. From the perspective of vascular–osteogenic coupling, this review reframes and synthesizes GelMA-based approaches for vascularized bone regeneration, grouping existing strategies into three categories: (i) intrinsic material design, in which pore architecture, microchannels, dynamic networks, and interfacial functionalization are used to guide vascular ingrowth; (ii) exogenous bioactive delivery, involving growth factors, extracellular vesicles, cells, and inorganic ions to enhance vascularization; and (iii) smart responsive strategies, including ROS/pH-responsive systems, sequential release, and external stimulation, which aim to recapitulate the evolving microenvironment during bone repair. This review further compares these strategies in terms of evidence level, reproducibility, and translational potential. Exogenous delivery systems currently have the strongest preclinical support, but issues related to dose standardization, burst release, and long-term safety remain unresolved. Intrinsic material programming is less extensively studied, yet may be more compatible with manufacturing consistency, sterilization, and engineering translation. Most stimuli-responsive systems, by contrast, remain largely at the small-animal or proof-of-concept stage. Future GelMA-based systems should therefore shift from increasing functional complexity toward improving predictability, reproducibility, and clinical feasibility. Compositionally defined and structurally controllable GelMA composites that integrate vascular regulation with mechanical support may provide a more realistic path for vascularized bone regeneration. Full article

Schwann cells (SCs) are critical effectors of peripheral nerve regeneration, and their interaction with biomaterial scaffolds is a key parameter in neural tissue engineering. This pilot study described and evaluated protocols for a morphological, quantitative, and morphometric analysis of SCs seeded on electrospun polyhydroxybutyrate (PHB) scaffolds using variable-pressure scanning electron microscopy (VP-SEM) under a low vacuum, without a metal coating. Six protocols were compared, varying the number of seeded cells (50,000 or 100,000) and the method used to label the seeded face of the scaffold: no marking, graphite pencil, or permanent ink (Sharpie). Confocal microscopy confirmed SC viability and adhesion. The VP-SEM analysis revealed that seeding 100,000 cells significantly increased the number of detectable cells on the scaffold surface. Graphite labeling was associated with higher cell counts and a more stellate morphology, consistent with the biocompatibility of carbon-based materials reported in the literature. Conversely, ink labeling appeared to inhibit SC adhesion. A refined protocol for measuring SC extensions using ImageJ’s ROI Manager and segmented line tools was also established. These findings provide practical methodological insights to improve the reliability and reproducibility of SC morphological analyses on ultra-thin polymeric scaffolds, with implications for peripheral nerve regeneration research. Full article

Sports injuries, especially musculoskeletal and neurological types from strenuous exercise, are a global public health challenge. Characterized by a high incidence and slow recovery, these injuries differ from typical trauma, often resulting in severe mechanical transmission loss and an imbalanced immune microenvironment. Consequently, standard interventions struggle to achieve true tissue regeneration. Gelatin, a collagen-derived biomaterial, offers RGD-mediated cell adhesion, MMP-responsive degradation, and high modifiability. These qualities make it an excellent foundation for biomimetic repair scaffolds. This paper reviews the design principles and recent advances in gelatin-based multifunctional hydrogels in sports medicine. First, we analyse their structure and engineering advantages. Next, we summarise strategies and mechanisms for modules like conductivity, antibacterial activity, self-healing, stimulus responsiveness, and tissue adhesion. The review links these modules to types of injuries: bone or cartilage, tendon or ligament, skeletal muscle, spinal cord, and peripheral nerve. It clarifies their clinical and translational value in remodelling immune microenvironments, regulating electrophysiology, promoting interfacial regeneration, and restoring motor function. This review provides focused insights from materials science and sports rehabilitation to advance precision treatments for sports injuries. Full article

Progranulin (PGRN) is a secreted protein composed of 7.5 granulin domains. The protein is implicated in various functions, including cell survival, inflammation, lysosomal homeostasis, tumorigenesis, and aging. Haploinsufficiency and complete loss of PGRN function cause the neurodegenerative disorders frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis type 11, respectively. In the nervous system, administration of exogenous PGRN has been shown to promote the survival of various nerve cell types under different pathological conditions and to stimulate neurite outgrowth in vitro and axonal regeneration in vivo. In the retina, PGRN dysfunction results in photoreceptor and retinal ganglion cell (RGC) loss, whereas PGRN administration promotes photoreceptor cell survival. In the present study, we analyzed whether a sustained intravitreal administration of PGRN promotes the survival of axotomized RGCs and the regrowth of the lesioned axons. To this end, we generated a PGRN-overexpressing clonal neural stem cell line and injected the cells into the vitreous cavity of a mouse optic nerve crush model. The progression of the lesion-induced degeneration of RGCs was studied at different time points after the nerve crush. The regeneration of the injured RGC axons into the distal optic nerve stump was analyzed one month after nerve lesioning. We found that the intravitreally administered PGRN slowed the degeneration of the injured RGCs for up to four months, the latest post-lesion interval analyzed. Furthermore, PGRN stimulated the regeneration of some RGC axons over long distances into the distal optic nerve stumps. Taken together, our results identify PGRN as a novel neurotrophic factor for retinal ganglion cells. Full article

Traumatic injuries often result in nerve tissue damage and functional deficits due to limited regeneration. Silk fibroin, a biopolymer with inherent biocompatibility and tunable properties, is a promising material for 3D-bioprinted neural tissue scaffolds. This review highlights recent advancements in silk-derived composite scaffolds, often incorporating additional materials like collagen or conductive polymers to enhance their performance. This review examines how material composition, scaffold architecture, and fabrication strategy influence biological response and functional recovery. This comprehensive review follows PRISMA guidelines and uses comprehensive searches of PubMed, MEDLINE, Embase, Web of Science, Cochrane Central, and ClinicalTrials.gov for studies published through 2025. Studies were screened for eligibility based on substance type, mechanical properties, production methods, and outcomes. Findings were synthesized qualitatively. Twelve studies were included, comprising rat (50%), canine (8.3%), and in vitro (41.7%) models. Analysis reveals that silk fibroin acts as a highly adaptable mechanical backbone. It can consistently integrate with bioactive additives (collagen, dECM) or conductive polymers (Polypyrrole, MXene) to meet specific therapeutic demands. For spinal cord injuries, composites reached a compressive modulus capable of resisting physiological pressures and preventing scaffold collapse. In soft tissue applications, silk–hydrogel blends provided localized release of exosomes and small molecules during the acute injury phase, reducing neuroinflammatory markers. Additionally, adding conductive materials allowed the scaffolds to bridge electrical gaps and promote Schwann cell proliferation and neuronal differentiation. Furthermore, 3D bioprinting enabled the creation of defined microchannels that replicate native fascicular architecture. In vivo outcomes consistently showed superior axonal regeneration, myelination, and synaptic reconnection compared to controls, correlating with significant improvements in electrophysiological and motor function. This review highlights the clinical potential of silk fibroin-based 3D-printed biomaterials for nerve regeneration, including neural repair and neural tissue engineering. More recent studies place greater emphasis on integrating mechanical, architectural, and biological considerations into scaffold design, resulting in increasingly multifunctional scaffold systems. Despite promising efficacy, the heterogeneity of fabrication methods and the predominance of rodent models highlight the need for standardized protocols and evaluations in relevant models to facilitate clinical translation. Full article

The current study illustrates the modeling of a biocompatible poly γ-glutamic acid (PGA)–chitosan–rGO nanocomposite hydrogel scaffold, which showed a promising novel scaffold for stimulating central nerve regeneration that addresses the shortcomings of recent therapies and improves tissue engineering, controls inflammation, and restores lost functions after spinal cord injuries (SCIs). In the implementation part of the study, the COMSOL program’s top-notch modeling of a detailed investigation of how a scaffold’s in vivo diffusion affects injured neurons. Michaelis–Menten kinetics is used to characterize the enzyme process of releasing the outer covering shell of the scaffold, PGA, from a biomaterial matrix to the nerve cell. Results suggested that the injectable hydrogel scaffold theoretically reduces extracellular glutamate concentrations, presenting a potential mechanism to mitigate localized excitotoxicity. Future in vivo experimental validation is required to determine if this reduction prevents neural cell death Full article

Artificial nerve guidance conduits (NGCs) have gained significant attention in the field of peripheral nerve regeneration for the treatment of critically sized nerve defects. Nanotechnology-based NGCs are being explored as potential solutions for repairing and reconstructing peripheral nerve injuries due to their unique structure and topography. In this study, we present a novel core–sheath GelMA/PCL nanofiber construct fabricated through electrospinning and phase separation methods. The core–sheath GelMA/PCL nanofibers replicate the topological morphology of the native extracellular matrix (ECM). The outer layer, composed of GelMA, serves as an “adhesion domain” facilitating direct interaction with surrounding cells and tissues while improving wettability, integrin-mediated cell adhesion/attachment, and degradation. PCL, acting as the “elastic domain” within the nanofibers, enhances mechanical properties, maintains long-term stability of the NGCs, and enables controlled release of GelMA. Histomorphometric analysis along with electrophysiological and behavioral assessments demonstrate that these core–sheath GelMA/PCL nanofiber-based NGCs can activate endogenous mechanisms for peripheral nerve repair while promoting sensory/motor nerve regeneration and functional recovery. Overall, our findings demonstrate that GelMA/PCL nanofibers within the nuclear sheath can effectively remodel the nerve regeneration microenvironment by integrating “mechanical- biochemical” signals, thereby offering a novel strategy for addressing critical-size nerve defects. Full article