Angiogenesis is a key process in regenerative medicine generally, as well as in the specific field of nerve regeneration. However, no convenient and objective method for evaluating the angiogenesis of tissue-engineere...Angiogenesis is a key process in regenerative medicine generally, as well as in the specific field of nerve regeneration. However, no convenient and objective method for evaluating the angiogenesis of tissue-engineered nerves has been reported. In this study, tissue-engineered nerves were constructed in vitro using Schwann cells differentiated from rat skin-derived precursors as supporting cells and chitosan nerve conduits combined with silk fibroin fibers as scaffolds to bridge 10-mm sciatic nerve defects in rats. Four weeks after surgery, three-dimensional blood vessel reconstructions were made through MICROFIL perfusion and micro-CT scanning, and parameter analysis of the tissue-engineered nerves was performed. New blood vessels grew into the tissue-engineered nerves from three main directions： the proximal end, the distal end, and the middle. The parameter analysis of the three-dimensional blood vessel images yielded several parameters, including the number, diameter, connection, and spatial distribution of blood vessels. The new blood vessels were mainly capillaries and microvessels, with diameters ranging from 9 to 301 μm. The blood vessels with diameters from 27 to 155 μm accounted for 82.84% of the new vessels. The microvessels in the tissue-engineered nerves implanted in vivo were relatively well-identified using the MICROFIL perfusion and micro-CT scanning method, which allows the evaluation and comparison of differences and changes of angiogenesis in tissue-engineered nerves implanted in vivo.展开更多
BACKGROUND： Schwann cells are the most commonly used cells for tissue-engineered nerves. However, autologous Schwann cells are of limited use in a clinical context, and allogeneic Schwann cells induce immunological r...BACKGROUND： Schwann cells are the most commonly used cells for tissue-engineered nerves. However, autologous Schwann cells are of limited use in a clinical context, and allogeneic Schwann cells induce immunological rejections. Cells that do not induce immunological rejections and that are relatively easy to acquire are urgently needed for transplantation. OBJECTIVE： To bridge sciatic nerve defects using tissue engineered nerves constructed with neural tissue-committed stem cells （NTCSCs） derived from bone marrow; to observe morphology and function of rat nerves following bridging; to determine the effect of autologous nerve transplantation, which serves as the gold standard for evaluating efficacy of tissue-engineered nerves. DESIGN, TIME AND SETTING： This randomized, controlled, animal experiment was performed in the Anatomical Laboratory and Biomedical Institute of the Second Military Medical University of Chinese PLA between September 2004 and April 2006. MATERIALS： Five Sprague Dawley rats, aged 1 month and weighing 100-150 g, were used for cell culture. Sixty Sprague Dawley rats aged 3 months and weighing 220-250 g, were used to establish neurological defect models. Nestin, neuron-specific enolase （NSE）, glial fibrillary acidic protein （GFAP）, and S-100 antibodies were provided by Santa Cruz Biotechnology, Inc., USA. Acellular nerve grafts were derived from dogs. METHODS： All rats, each with 1-cm gap created in the right sciatic nerve, were randomly assigned to three groups. Each group comprised 20 rats. Autograft nerve transplantation group： the severed 1-cm length nerve segment was reverted, but with the two ends exchanged; the proximal segment was sutured to the distal sciatic nerve stump and the distal segment to the proximal stump. Blank nerve scaffold transplantation group： a 1-cm length acellular nerve graft was used to bridge the sciatic nerve gap. NTCSC engineered nerve transplantation group： a 1-cm length acellular nerve graft, in which NTCSCs were inoculated, was used to bridge the sciatic nerve gap. MAIN OUTCOME MEASURES： Following surgery, sciatic nerve functional index and electrophysiology functions were evaluated for nerve conduction function, including conduction latency, conduction velocity, and action potential peak. Horseradish peroxidase （HRP, 20%） was injected into the gastrocnemius muscle to retrogradely label the 1-4 and L5 nerve ganglions, as well as neurons in the anterior horn of the spinal cord, in the three groups. Positive expression of nestin, NSE, GFAP, and S-100 were determined using an immunofluorescence double-labeling method. RESULTS： NTCSCs differentiated into neuronal-like cells and glial-like cells within 12 weeks after NTCSC engineered nerve transplantation. HRP retrograde tracing displayed a large amount of HRP-labeled neurons in I-45 nerve ganglions, as well as the anterior horn of the spinal cord, in both the autograft nerve transplantation and the NTCSC engineered nerve transplantation groups. However, few HRP-labeled neurons were detected in the blank nerve scaffold transplantation group. Nerve bridges in the autograft nerve transplantation and NTCSC engineered nerve transplantation groups exhibited similar morphology to normal nerves. Neither fractures or broken nerve bridges nor neuromas were found after bridging the sciatic nerve gap with NTCSCs-inoculated acellular nerve graft, indicating repair. Conduction latency, action potential, and conduction velocity in the NTCSC engineered nerve transplantation group were identical to the autograft nerve transplantation group （P 〉 0.05）, but significantly different from the blank nerve scaffold transplantation group （P 〈 0.05）. CONCLUSION＂ NTCSC tissue-engineered nerves were able to repair injured nerves and facilitated restoration of nerve conduction function, similar to autograft nerve transplantation. ＂展开更多
Three articles regarding the use of nerve fragments bridging regeneration chambers, three-dimensional bionic nerve conduits and multiwalled carbon nanotubes for repair of sciatic nerve injury were reported in Neural R...Three articles regarding the use of nerve fragments bridging regeneration chambers, three-dimensional bionic nerve conduits and multiwalled carbon nanotubes for repair of sciatic nerve injury were reported in Neural Regeneration Research. We hope that our readers find these papers useful to their research.展开更多
Damage to peripheral nerve tissue may cause loss of function in both the nerve and the targeted muscles it innervates. This study compared the repair capability of engineered nerve conduit （ENC）, engineered fibrobla...Damage to peripheral nerve tissue may cause loss of function in both the nerve and the targeted muscles it innervates. This study compared the repair capability of engineered nerve conduit （ENC）, engineered fibroblast conduit （EFC）, and autograft in a 10-mm tibial nerve gap. ENCs were fabricated utilizing primary fibroblasts and the nerve cells of rats on embryonic day 15 （E 15）. EFCs were fabricated utilizing primary fi- broblasts only. Following a 12-week recovery, nerve repair was assessed by measuring contractile properties in the medial gastrocnemius muscle, distal motor nerve conduction velocity in the lateral gastrocnemius, and histology of muscle and nerve. The autografts, ENCs and EFCs reestablished 96%, 87% and 84% of native distal motor nerve conduction velocity in the lateral gastrocnemius, 100%, 44% and 44% of native specific force of medical gastrocnemius, and 63%, 61% and 67% of native medial gastrocnemius mass, re- spectively. Histology of the repaired nerve revealed large axons in the autograft, larger but fewer axons in the ENC repair, and many smaller axons in the EFC repair. Muscle histology revealed similar muscle fiber cross-sectional areas among autograft, ENC and EFC repairs. In conclusion, both ENCs and EFCs promot- ed nerve regeneration in a 10-mm tibial nerve gap repair, suggesting that the El5 rat nerve cells may not be necessary for nerve regeneration, and EFC alone can suffice for peripheral nerve injury repair.展开更多
Objective Peripheral nerve injury leads to various degrees of functional defects.Nerve guidance conduits are considered as a new promising scaffold for peripheral nerve repair.However,conventional single-material nerv...Objective Peripheral nerve injury leads to various degrees of functional defects.Nerve guidance conduits are considered as a new promising scaffold for peripheral nerve repair.However,conventional single-material nerve conduits have shown limited efficacy in protecting cells from posttraumatic inflammation.This study aims to develop a single-process PLGA-based nerve conduit loaded with melatonin to enhance the biological performance of pure PLGA materials by suppressing oxidative stress and inflammatory responses.Methods The PLGA conduit is prepared with dry-jet wet spinning methods.The melatonin is integrated into PLGA conduits directly with the single-step process.Scanning electrical microscope observation,FTIR test,degradation test and drug releasing test were performed to characterize the morphology and physical properties of the nerve conduits.Schwann cells were cultured to test the biocompatibility of the prepared nerve conduits.Oxidative stress was applied on Schwann cell using hydrogen peroxide.Then the protecting effects of the nerve conduits were tested on the hydrogen peroxide-treated cells.SD rat sciatic model was applied to test the conduit in vivo.Results The melatonin is successfully integrated into the nerve conduit with the dry-jet wet spinning method.Cell adhesion and proliferation test of the Schwann cell indicated that the nerve conduits exhibit excellent biocompatibility.While the mitochondrial morphology observation and JC-1 potential detection also showed protecting effects on Mitochondria.The q-PCR analysis showed nerve conduits reduced cellular oxidative stress and inflammatory responses while enhancing cellular proliferation.A marked enhancement on SD rat sciatic nerve regeneration was also observed on melatonin loaded conduits.Conclusions By integrating melatonin into PLGA using the dryjet wet-spinning technique,the conduit is endowed with multiple functional advantages,including antiinflammatory,antioxidant,and neuroprotective properties.This approach is expected to create a favorable microenvironment for nerve tissue regeneration and provide a new perspective for the treatment of peripheral nerve injuries.展开更多
Stroke and traumatic brain injury lead to upper motor neuron syndrome,which is characterized by muscle spasticity or paresis of varying severity depending on the lesion’s location and extent.Current treatments are mo...Stroke and traumatic brain injury lead to upper motor neuron syndrome,which is characterized by muscle spasticity or paresis of varying severity depending on the lesion’s location and extent.Current treatments are mostly symptomatic with limited efficacy and significant side effects.Nerve transfer techniques,such as the contralateral L4 ventral root transfer in animal models and C7 root transfer in both animal and clinical studies,have been shown to reduce spasticity and improve function in upper motor neuron syndrome;however,they lack selectivity.Our hypothesis is that using a selective peripheral donor nerve from the contralateral side,rather than the entire nerve root,may represent an effective nerve transfer and provide a robust basis for future research on selective muscle reinnervation in upper motor neuron syndrome.Ten rats underwent a contralateral ulnar-to-ulnar nerve transfer procedure.Electrophysiological measurements were conducted twelve weeks post-surgery to assess successful reinnervation of the contralateral flexor carpi ulnaris muscle.Additionally,muscle biopsies of the reinnervated flexor carpi ulnaris were harvested to examine the muscle fiber type composition,cross-sectional area,and collagen content as well as compare them to naive counterparts.Axon quantification of the reinnervated nerves was also performed.All rats recovered uneventfully,maintaining the use of both paws post-surgery.Electrophysiological tests confirmed the successful reinnervation of the flexor carpi ulnaris muscle.Muscle fiber type composition,cross-sectional area,and collagen content did not show statistically significant changes.Axon counts indicated successful nerve regeneration without architectural disruption.In conclusion,we were able to demonstrate this novel contralateral nerve transfer model’s feasibility,reproducibility,and safety as well as achieve effective muscle reinnervation.This model provides a valuable tool for further research on selective muscle reinnervation and treatment of upper motor neuron syndrome,with potential implications for improving clinical outcomes in stroke and traumatic brain injury patients.展开更多
We have previously shown the success of polyethylene glycol fusion repair of segmental-loss peripheral nerve injuries in rats using freshly harvested,viable peripheral nerve allografts that can conduct action potentia...We have previously shown the success of polyethylene glycol fusion repair of segmental-loss peripheral nerve injuries in rats using freshly harvested,viable peripheral nerve allografts that can conduct action potentials.Because clinical application of polyethylene glycol fusion with viable peripheral nerve allografts demands pre-transplant donor tissue storage,we developed a protocol for ex vivo storage of rat sciatic nerves as viable peripheral nerve allografts,preserving many axons for up to 5 days.The current study evaluated the in vivo use of these stored viable peripheral nerve allografts.We hypothesized that stored viable peripheral nerve allografts with viable axons would enable successful in vivo repair of segmental-loss peripheral nerve injuries via polyethylene glycol-fusion.Polyethylene glycol-fused viable peripheral nerve allografts were classified as successful if they produced significantly improved locomotor recovery,as evaluated by the sciatic functional index,within 8 weeks post-repair.Many Sprague-Dawley and Lewis rats with successfully polyethylene glycol-fused viable peripheral nerve allografts had significantly improved sciatic functional index scores beginning at 5 weeks post-operatively.There was no significant difference in the efficiency and extent of successful polyethylene glycol fusion between stored and freshly harvested viable peripheral nerve allografts.In contrast,rats with non-fused negative control viable peripheral nerve allografts showed no recovery by 8 weeks post-operatively.Additional confirmatory outcome measures included in vivo compound action potentials and assessments of axon morphometry.These results suggest that viable peripheral nerve allografts can be stored and later used for successful polyethylene glycol fusion repair of segmental-loss peripheral nerve injuries.展开更多
Peripheral nerve injury is a complex condition presenting significant clinical treatment challenges due to the limited regenerative capacity of peripheral nerves.Nerve conduits have been seen as a promising strategy t...Peripheral nerve injury is a complex condition presenting significant clinical treatment challenges due to the limited regenerative capacity of peripheral nerves.Nerve conduits have been seen as a promising strategy to overcome the shortage of other treatment options(e.g.,nerve graft).However,nerve regeneration occurs within a complex environment,and elaborate modulation is needed to meet repair requirements.The aim of this study was to investigate and explore a multifunctional nerve conduit with reactive oxygen species clearing,immune modulation to reshape the regenerative environment,and topographic cues and electrical signals to guide nerve growth.We developed an electroactive nerve guidance conduit composed of polylactic-glycolic acid and carbon nanotubes with an oriented structure using electrospinning and modified it with mussel-inspired polydopamine combining neurotrophin-3.The resulting nerve scaffold exhibited favorable orientation,electrical conductivity,and mechanical properties.Continuous release of neurotrophin-3 from the nerve conduit supported nerve regeneration throughout the repair process.In vitro assessments confirmed the cytocompatibility,reactive oxygen species scavenging,and immune regulation capabilities of the nerve scaffolds.In a rat sciatic nerve defect model,the nerve scaffolds effectively prevented muscle atrophy and promoted nerve regeneration and functional recovery over a 12-week period.These findings suggest that polydopamine-modified,electroactive,oriented nerve guidance conduits with multiple bioactive functions hold great promise for the repair of peripheral nerve injuries.展开更多
Bone is highly innervated,and its regeneration is significantly nerve-dependent.Extensive evidence suggests that the nervous system plays an active role in bone metabolism and development by modulating osteoblast and ...Bone is highly innervated,and its regeneration is significantly nerve-dependent.Extensive evidence suggests that the nervous system plays an active role in bone metabolism and development by modulating osteoblast and osteoclast activity.However,the majority of research to date has focused on the direct effects of peripheral nerves and their neurotransmitters on bone regeneration.Emerging studies have begun to reveal a more intricate role of nerves in regulating the immune microenvironment,which is crucial for bone regeneration.This review summarizes how nerves influence bone regeneration through modulation of the immune microenvironment.We first discuss the changes in peripheral nerves during the regenerative process.We then describe conduction and paracrine pathways through which nerves affect the osteogenic immune microenvironment,emphasizing nerves,neural factors,and their impacts.Our goal is to deepen the understanding of the nerve-immune axis in bone regeneration.A better grasp of how nerves influence the osteogenic immune microenvironment may lead to new strategies that integrate the nervous,immune,and skeletal systems to promote bone regeneration.展开更多
Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological prop...Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity,highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury;however,its role in modulating neuroinflammation post-peripheral nerve injury remains unknown.Here,we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms.Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel,we evaluated structural and functional recovery,macrophage phenotype alteration,specific cytokine expression,and changes in related signaling molecules in vivo.Similar parameters were evaluated in vitro using monocyte/macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel-coated plates in complete medium.These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages.Additionally,porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro.Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway,providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.展开更多
Neural injuries can cause considerable functional impairments,and both central and peripheral nervous systems have limited regenerative capacity.The existing conventional pharmacological treatments in clinical practic...Neural injuries can cause considerable functional impairments,and both central and peripheral nervous systems have limited regenerative capacity.The existing conventional pharmacological treatments in clinical practice show poor targeting,rapid drug clearance from the circulatory system,and low therapeutic efficiency.Therefore,in this review,we have first described the mechanisms underlying nerve regeneration,characterized the biomaterials used for drug delivery to facilitate nerve regeneration,and highlighted the functionalization strategies used for such drug-delivery systems.These systems mainly use natural and synthetic polymers,inorganic materials,and hybrid systems with advanced drug-delivery abilities,including nanoparticles,hydrogels,and scaffoldbased systems.Then,we focused on comparing the types of drug-delivery systems for neural regeneration as well as the mechanisms and challenges associated with targeted delivery of drugs to facilitate neural regeneration.Finally,we have summarized the clinical application research and limitations of targeted delivery of these drugs.These biomaterials and drug-delivery systems can provide mechanical support,sustained release of bioactive molecules,and enhanced intercellular contact,ultimately reducing cell apoptosis and enhancing functional recovery.Nevertheless,immune reactions,degradation regulation,and clinical translations remain major unresolved challenges.Future studies should focus on optimizing biomaterial properties,refining delivery precision,and overcoming translational barriers to advance these technologies toward clinical applications.展开更多
Retinal ganglion cells,a crucial component of the central nervous system,are often affected by irreversible visual impairment due to various conditions,including trauma,tumors,ischemia,and glaucoma.Studies have shown ...Retinal ganglion cells,a crucial component of the central nervous system,are often affected by irreversible visual impairment due to various conditions,including trauma,tumors,ischemia,and glaucoma.Studies have shown that the optic nerve crush model and glaucoma model are commonly used to study retinal ganglion cell injury.While these models differ in their mechanisms,both ultimately result in retinal ganglion cell injury.With advancements in high-throughput technologies,techniques such as microarray analysis,RNA sequencing,and single-cell RNA sequencing have been widely applied to characterize the transcriptomic profiles of retinal ganglion cell injury,revealing underlying molecular mechanisms.This review focuses on optic nerve crush and glaucoma models,elucidating the mechanisms of optic nerve injury and neuron degeneration induced by glaucoma through single-cell transcriptomics,transcriptome analysis,and chip analysis.Research using the optic nerve crush model has shown that different retinal ganglion cell subtypes exhibit varying survival and regenerative capacities following injury.Single-cell RNA sequencing has identified multiple genes associated with retinal ganglion cell protection and regeneration,such as Gal,Ucn,and Anxa2.In glaucoma models,high-throughput sequencing has revealed transcriptomic changes in retinal ganglion cells under elevated intraocular pressure,identifying genes related to immune response,oxidative stress,and apoptosis.These genes are significantly upregulated early after optic nerve injury and may play key roles in neuroprotection and axon regeneration.Additionally,CRISPR-Cas9 screening and ATAC-seq analysis have identified key transcription factors that regulate retinal ganglion cell survival and axon regeneration,offering new potential targets for neurorepair strategies in glaucoma.In summary,single-cell transcriptomic technologies provide unprecedented insights into the molecular mechanisms underlying optic nerve injury,aiding in the identification of novel therapeutic targets.Future researchers should integrate advanced single-cell sequencing with multi-omics approaches to investigate cell-specific responses in retinal ganglion cell injury and regeneration.Furthermore,computational models and systems biology methods could help predict molecular pathways interactions,providing valuable guidance for clinical research on optic nerve regeneration and repair.展开更多
Autologous nerve transplantation is currently recognized as the gold standard for treating seve re peripheral nerve injuries in clinical practice.Howeve r,challenges such as a limited supply of donors,complications in...Autologous nerve transplantation is currently recognized as the gold standard for treating seve re peripheral nerve injuries in clinical practice.Howeve r,challenges such as a limited supply of donors,complications in the donor area,and the formation of neuromas necessitate the optimization of existing transplantation strategies.Additionally,the development of new and promising repair methods is a critical issue in the field of peripheral nerve research.The purpose of this article is to compare the advantages and disadvantages of autologous,allogeneic,decellularized nerve grafts,and cell-composite graft,as well as to summarize the diffe rences in their prognostic factors and associated adve rse events.The length,diamete r,polarity,and sensory or motor origin of autografts all influence axonal regeneration.While pre-denaturation treatment can accele rate early regeneration,long-term functional outcomes of autografts do not show significant differences compared with fresh autologous grafts.For decellularized nerve grafts,defect length is identified as an independent risk factor,and the internal microenvironment(delayed angiogenesis,Schwann cell senescence,and reduced T-cell infiltration)is considered a key factor limiting long-segment regeneration.Additionally,the decellula rization process(whether chemical,physical,or supercritical CO_(2))affects the integrity of the extracellular matrix and the presence of immune residuals,which directly impacts axonal guidance and host integration.Common adve rse events following autograft transplantation include donor site numbness,neuromas,and scarring.In contrast,adverse events associated with decellularized nerve graft transplantation may present as inflammatory reactions,excessive scar prolife ration,and misalignment or reconnection of regenerating axons,which can lead to sensory-m otor cross-innervation.To mitigate these issues,combining decellularized nerve grafts with autologous Schwann cells,mesenchymal stem cells,or induced pluripotent stem cellderived cells may help bridge the gap with autografts.However,the fact that structural recovery does not necessarily lead to functional recovery needs further clarification.Future research should establish la rge animal models to replicate the limits of human regenerative capacity,use gene editing to enhance the phenotype and microenvironment of transplanted cells,and develop a mild combined decellularization process that maximizes the preservation of natural nerve grafts.Through multidimensional optimization,decellularized nerve grafts have the potential to ultimately re place autograft transplantation,enabling precise repair of individualized,long-segment,and complex nerve defects.展开更多
Traumatic axonal lesions of peripheral nerves disrupt neuronal connections with their targets,resulting in the loss of motor and sensory functions.Despite the peripheral nervous system’s capacity for axonal regrowth,...Traumatic axonal lesions of peripheral nerves disrupt neuronal connections with their targets,resulting in the loss of motor and sensory functions.Despite the peripheral nervous system’s capacity for axonal regrowth,this may lead to permanent impairements resulting in a loss of quality of life and a high socioeconomic burden.展开更多
Traditional nerve repair methods,such as autologous nerve grafting and allogeneic nerve grafting,face issues such as donor shortage,functional loss,and immune rejection.Decellularized extracellular matrix-based grafts...Traditional nerve repair methods,such as autologous nerve grafting and allogeneic nerve grafting,face issues such as donor shortage,functional loss,and immune rejection.Decellularized extracellular matrix-based grafts have emerged as highly promising alternatives,capable of uniquely recreating the natural neural mic roenvironment,promoting host cell remodeling,and ultimately enhancing functional neural regeneration.This review comprehensively analyzes the key mechanisms of peripheral nerve injury and regeneration,focusing on contemporary therapeutic strategies for key aspects such as axonal apoptosis inhibition,enhanced intrinsic regenerative capacity,construction of regenerative microenvironment,and prevention of target organ atrophy.Findings from this review has shown that decellularized extra cellular matrix grafts can promote the migration,prolife ration,and differentiation of nerve cells by providing physical suppo rt,chemical signals,and mechanical stability.Decellularized extracellular matrix grafts are mainly used as ne rve conduits,scaffolds,hydrogels,and3D printing inks.Decellularized extra cellular matrix grafts have demonstrated significant advantages in promoting nerve regeneration by regulating the prolife ration and differentiation of Schwann cells,improving the neural microenvironment,reducing inflammato ry responses,and promoting angiogenesis.Additionally,decellularized extracellular matrix grafts can se rve as drug carrie rs,enabling the controlled release of growth factors,which further enhances nerve regeneration.However,these grafts also have some limitations,including the presence of immunogenic residues,inadequate mechanical prope rties,inter-batch variability,and uncontrollable degradation rates.Future research should focus on optimizing the decellularization process,enhancing the mechanical prope rties of decellularized extracellular matrix grafts,reducing immunogenicity,improving biocompatibility and safety,and developing new composite mate rials.Furthermore,exploring their application potential in complex nerve injuries,such as diabetic neuropathy,is crucial to meet the needs of peripheral nerve regeneration and repair.展开更多
1Introduction A 25-year-old woman presented with a 3-month history of otalgia and aural fullness in the left ear,without associated otological or systemic symptoms.Her medical history was unremarkable,and she denied a...1Introduction A 25-year-old woman presented with a 3-month history of otalgia and aural fullness in the left ear,without associated otological or systemic symptoms.Her medical history was unremarkable,and she denied any history of hepatitis,hypertension,diabetes,cardiovascular disease,or other significant conditions.The patient was diagnosed with external auditory canal cholesteatoma and subsequently underwent canalplasty under general anesthesia.Routine anesthetic drugs,including 2%lidocaine,dexamethasone,propofol,sufentanil,rocuronium bromide,ondansetron,flurbiprofen axetil,neostigmine,and atropine,were used during surgery and anesthesia recovery.No significant events were noted,and the patient experienced only a blood loss of 10 mL.展开更多
Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells.However,adult tissue–derived mesenchymal stem cells en...Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells.However,adult tissue–derived mesenchymal stem cells encounter various obstacles,including limited tissue sources,invasive acquisition methods,cellular heterogeneity,purification challenges,cellular senescence,and diminished pluripotency and proliferation over successive passages.In this study,we used induced pluripotent stem cell-derived mesenchymal stem cells,known for their self-renewal capacity,multilineage differentiation potential,and immunomodulatory characteristics.We used induced pluripotent stem cell-derived mesenchymal stem cells in conjunction with acellular nerve allografts to address a 10 mm-long defect in a rat model of sciatic nerve injury.Our findings reveal that induced pluripotent stem cell-derived mesenchymal stem cells exhibit survival for up to 17 days in a rat model of peripheral nerve injury with acellular nerve allograft transplantation.Furthermore,the combination of acellular nerve allograft and induced pluripotent stem cell-derived mesenchymal stem cells significantly accelerates the regeneration of injured axons and improves behavioral function recovery in rats.Additionally,our in vivo and in vitro experiments indicate that induced pluripotent stem cell-derived mesenchymal stem cells play a pivotal role in promoting neovascularization.Collectively,our results suggest the potential of acellular nerve allografts with induced pluripotent stem cell-derived mesenchymal stem cells to augment nerve regeneration in rats,offering promising therapeutic strategies for clinical translation.展开更多
Tactile feedback is critical for human interaction with external information.Similarly,tactile feedback can enrich the user's sensations when using prosthesis.To explore a potential scheme for tactile feedback,thi...Tactile feedback is critical for human interaction with external information.Similarly,tactile feedback can enrich the user's sensations when using prosthesis.To explore a potential scheme for tactile feedback,this study applied a non-inva-sive Transcutaneous Electrical Nerve Stimulation(TENS)to elicit tactile sensations in the hand,which involved median nerve,ulnar nerve,and radial nerve.Ten able-bodied subjects(8 males,2 females)were recruited to participate in the study.An array of 4×2 electrodes was positioned on the medial aspect of the brachii muscle's short head in the upper arm,which is in proximity to the median nerve,ulnar nerve,and radial nerve.Different electrode pairs were randomly selected to elicit distinct sensations at various positions on the hand,and the subjects reported the sensory areas.Then,the sensory areas and sensory thresholds were confirmed through psychophysical methods.According to the experimental results,tactile sensations were elicited at different locations on the subjects'hand through TENS of different electrode pairs.All subjects reported extensive and detailed sensory areas in the fingers,palm,and dorsum,corresponding to the sensory innervation areas of different nerves.The study effectively demonstrated the ability of TENS in evoking tactile feedback in the hand,paving the way for future optimization and development of prosthetic hands.展开更多
Dear Editor,Dorsal pontine lesions may cause a variety of complex neuro-ophthalmic deficits,including horizontal gaze palsy(HGP),internuclear ophthalmoplegia,one-and-ahalf syndrome,abducens nerve palsy,skew deviation,...Dear Editor,Dorsal pontine lesions may cause a variety of complex neuro-ophthalmic deficits,including horizontal gaze palsy(HGP),internuclear ophthalmoplegia,one-and-ahalf syndrome,abducens nerve palsy,skew deviation,or any combination of these.Here we present a rare case of an adult patient who developed multiple complicated clinical manifestations after surgical removal of a pontine cavernous hemangioma(PCH).Our case highlights a single pontine lesion may involve complicated neural pathways and result in complicated symptoms and signs,in which abducens nerve palsy or skew deviation is easily missed when combined with HGP.展开更多
Phrenic nerve stimulation(PNS)may preserve diaphragm activation and mitigate multiorgan injury during mechanical ventilation(MV);however,a minimal invasive rat model integrating PNS with MV is lacking.We established a...Phrenic nerve stimulation(PNS)may preserve diaphragm activation and mitigate multiorgan injury during mechanical ventilation(MV);however,a minimal invasive rat model integrating PNS with MV is lacking.We established an omohyoid muscle-based PNS rat model combined with MV.Bilateral nerves were exposed within 20±2 min by transection at the intermediate tendon of omohyoid muscle,minimizing trauma and bleeding.Threshold stimulation(0.6±0.2 mA)correlated with body weight.Ventilator-synchronized stimulation increased compound muscle action potentials by~30%,whereas histology confirmed intact nerve.Physiological parameters remained stable throughout ventilation.This model provides a safe and scalable platform for mechanistic and preclinical studies on PNS-mediated protection against MV-induced organ injury.展开更多
基金supported by the National Natural Science Foundation of ChinaNo.81130080
文摘Angiogenesis is a key process in regenerative medicine generally, as well as in the specific field of nerve regeneration. However, no convenient and objective method for evaluating the angiogenesis of tissue-engineered nerves has been reported. In this study, tissue-engineered nerves were constructed in vitro using Schwann cells differentiated from rat skin-derived precursors as supporting cells and chitosan nerve conduits combined with silk fibroin fibers as scaffolds to bridge 10-mm sciatic nerve defects in rats. Four weeks after surgery, three-dimensional blood vessel reconstructions were made through MICROFIL perfusion and micro-CT scanning, and parameter analysis of the tissue-engineered nerves was performed. New blood vessels grew into the tissue-engineered nerves from three main directions： the proximal end, the distal end, and the middle. The parameter analysis of the three-dimensional blood vessel images yielded several parameters, including the number, diameter, connection, and spatial distribution of blood vessels. The new blood vessels were mainly capillaries and microvessels, with diameters ranging from 9 to 301 μm. The blood vessels with diameters from 27 to 155 μm accounted for 82.84% of the new vessels. The microvessels in the tissue-engineered nerves implanted in vivo were relatively well-identified using the MICROFIL perfusion and micro-CT scanning method, which allows the evaluation and comparison of differences and changes of angiogenesis in tissue-engineered nerves implanted in vivo.
基金Shanghai Municipal Natural Science Foundation,No.06ZR14108
文摘BACKGROUND： Schwann cells are the most commonly used cells for tissue-engineered nerves. However, autologous Schwann cells are of limited use in a clinical context, and allogeneic Schwann cells induce immunological rejections. Cells that do not induce immunological rejections and that are relatively easy to acquire are urgently needed for transplantation. OBJECTIVE： To bridge sciatic nerve defects using tissue engineered nerves constructed with neural tissue-committed stem cells （NTCSCs） derived from bone marrow; to observe morphology and function of rat nerves following bridging; to determine the effect of autologous nerve transplantation, which serves as the gold standard for evaluating efficacy of tissue-engineered nerves. DESIGN, TIME AND SETTING： This randomized, controlled, animal experiment was performed in the Anatomical Laboratory and Biomedical Institute of the Second Military Medical University of Chinese PLA between September 2004 and April 2006. MATERIALS： Five Sprague Dawley rats, aged 1 month and weighing 100-150 g, were used for cell culture. Sixty Sprague Dawley rats aged 3 months and weighing 220-250 g, were used to establish neurological defect models. Nestin, neuron-specific enolase （NSE）, glial fibrillary acidic protein （GFAP）, and S-100 antibodies were provided by Santa Cruz Biotechnology, Inc., USA. Acellular nerve grafts were derived from dogs. METHODS： All rats, each with 1-cm gap created in the right sciatic nerve, were randomly assigned to three groups. Each group comprised 20 rats. Autograft nerve transplantation group： the severed 1-cm length nerve segment was reverted, but with the two ends exchanged; the proximal segment was sutured to the distal sciatic nerve stump and the distal segment to the proximal stump. Blank nerve scaffold transplantation group： a 1-cm length acellular nerve graft was used to bridge the sciatic nerve gap. NTCSC engineered nerve transplantation group： a 1-cm length acellular nerve graft, in which NTCSCs were inoculated, was used to bridge the sciatic nerve gap. MAIN OUTCOME MEASURES： Following surgery, sciatic nerve functional index and electrophysiology functions were evaluated for nerve conduction function, including conduction latency, conduction velocity, and action potential peak. Horseradish peroxidase （HRP, 20%） was injected into the gastrocnemius muscle to retrogradely label the 1-4 and L5 nerve ganglions, as well as neurons in the anterior horn of the spinal cord, in the three groups. Positive expression of nestin, NSE, GFAP, and S-100 were determined using an immunofluorescence double-labeling method. RESULTS： NTCSCs differentiated into neuronal-like cells and glial-like cells within 12 weeks after NTCSC engineered nerve transplantation. HRP retrograde tracing displayed a large amount of HRP-labeled neurons in I-45 nerve ganglions, as well as the anterior horn of the spinal cord, in both the autograft nerve transplantation and the NTCSC engineered nerve transplantation groups. However, few HRP-labeled neurons were detected in the blank nerve scaffold transplantation group. Nerve bridges in the autograft nerve transplantation and NTCSC engineered nerve transplantation groups exhibited similar morphology to normal nerves. Neither fractures or broken nerve bridges nor neuromas were found after bridging the sciatic nerve gap with NTCSCs-inoculated acellular nerve graft, indicating repair. Conduction latency, action potential, and conduction velocity in the NTCSC engineered nerve transplantation group were identical to the autograft nerve transplantation group （P 〉 0.05）, but significantly different from the blank nerve scaffold transplantation group （P 〈 0.05）. CONCLUSION＂ NTCSC tissue-engineered nerves were able to repair injured nerves and facilitated restoration of nerve conduction function, similar to autograft nerve transplantation. ＂
文摘Three articles regarding the use of nerve fragments bridging regeneration chambers, three-dimensional bionic nerve conduits and multiwalled carbon nanotubes for repair of sciatic nerve injury were reported in Neural Regeneration Research. We hope that our readers find these papers useful to their research.
基金supported by a NIH,NIAMS,NIBIB funded grant R01 AR054778-05 and gift from the Barbara and Richard Raynor Medical Foundation Award
文摘Damage to peripheral nerve tissue may cause loss of function in both the nerve and the targeted muscles it innervates. This study compared the repair capability of engineered nerve conduit （ENC）, engineered fibroblast conduit （EFC）, and autograft in a 10-mm tibial nerve gap. ENCs were fabricated utilizing primary fibroblasts and the nerve cells of rats on embryonic day 15 （E 15）. EFCs were fabricated utilizing primary fi- broblasts only. Following a 12-week recovery, nerve repair was assessed by measuring contractile properties in the medial gastrocnemius muscle, distal motor nerve conduction velocity in the lateral gastrocnemius, and histology of muscle and nerve. The autografts, ENCs and EFCs reestablished 96%, 87% and 84% of native distal motor nerve conduction velocity in the lateral gastrocnemius, 100%, 44% and 44% of native specific force of medical gastrocnemius, and 63%, 61% and 67% of native medial gastrocnemius mass, re- spectively. Histology of the repaired nerve revealed large axons in the autograft, larger but fewer axons in the ENC repair, and many smaller axons in the EFC repair. Muscle histology revealed similar muscle fiber cross-sectional areas among autograft, ENC and EFC repairs. In conclusion, both ENCs and EFCs promot- ed nerve regeneration in a 10-mm tibial nerve gap repair, suggesting that the El5 rat nerve cells may not be necessary for nerve regeneration, and EFC alone can suffice for peripheral nerve injury repair.
文摘Objective Peripheral nerve injury leads to various degrees of functional defects.Nerve guidance conduits are considered as a new promising scaffold for peripheral nerve repair.However,conventional single-material nerve conduits have shown limited efficacy in protecting cells from posttraumatic inflammation.This study aims to develop a single-process PLGA-based nerve conduit loaded with melatonin to enhance the biological performance of pure PLGA materials by suppressing oxidative stress and inflammatory responses.Methods The PLGA conduit is prepared with dry-jet wet spinning methods.The melatonin is integrated into PLGA conduits directly with the single-step process.Scanning electrical microscope observation,FTIR test,degradation test and drug releasing test were performed to characterize the morphology and physical properties of the nerve conduits.Schwann cells were cultured to test the biocompatibility of the prepared nerve conduits.Oxidative stress was applied on Schwann cell using hydrogen peroxide.Then the protecting effects of the nerve conduits were tested on the hydrogen peroxide-treated cells.SD rat sciatic model was applied to test the conduit in vivo.Results The melatonin is successfully integrated into the nerve conduit with the dry-jet wet spinning method.Cell adhesion and proliferation test of the Schwann cell indicated that the nerve conduits exhibit excellent biocompatibility.While the mitochondrial morphology observation and JC-1 potential detection also showed protecting effects on Mitochondria.The q-PCR analysis showed nerve conduits reduced cellular oxidative stress and inflammatory responses while enhancing cellular proliferation.A marked enhancement on SD rat sciatic nerve regeneration was also observed on melatonin loaded conduits.Conclusions By integrating melatonin into PLGA using the dryjet wet-spinning technique,the conduit is endowed with multiple functional advantages,including antiinflammatory,antioxidant,and neuroprotective properties.This approach is expected to create a favorable microenvironment for nerve tissue regeneration and provide a new perspective for the treatment of peripheral nerve injuries.
基金supported by the European Research Council(ERC)under the European Union’s Horizon 2020 Research and Innovation Programme,No.810346.
文摘Stroke and traumatic brain injury lead to upper motor neuron syndrome,which is characterized by muscle spasticity or paresis of varying severity depending on the lesion’s location and extent.Current treatments are mostly symptomatic with limited efficacy and significant side effects.Nerve transfer techniques,such as the contralateral L4 ventral root transfer in animal models and C7 root transfer in both animal and clinical studies,have been shown to reduce spasticity and improve function in upper motor neuron syndrome;however,they lack selectivity.Our hypothesis is that using a selective peripheral donor nerve from the contralateral side,rather than the entire nerve root,may represent an effective nerve transfer and provide a robust basis for future research on selective muscle reinnervation in upper motor neuron syndrome.Ten rats underwent a contralateral ulnar-to-ulnar nerve transfer procedure.Electrophysiological measurements were conducted twelve weeks post-surgery to assess successful reinnervation of the contralateral flexor carpi ulnaris muscle.Additionally,muscle biopsies of the reinnervated flexor carpi ulnaris were harvested to examine the muscle fiber type composition,cross-sectional area,and collagen content as well as compare them to naive counterparts.Axon quantification of the reinnervated nerves was also performed.All rats recovered uneventfully,maintaining the use of both paws post-surgery.Electrophysiological tests confirmed the successful reinnervation of the flexor carpi ulnaris muscle.Muscle fiber type composition,cross-sectional area,and collagen content did not show statistically significant changes.Axon counts indicated successful nerve regeneration without architectural disruption.In conclusion,we were able to demonstrate this novel contralateral nerve transfer model’s feasibility,reproducibility,and safety as well as achieve effective muscle reinnervation.This model provides a valuable tool for further research on selective muscle reinnervation and treatment of upper motor neuron syndrome,with potential implications for improving clinical outcomes in stroke and traumatic brain injury patients.
基金National Institutes of Health(NIH)R01-NS128086 grant(to GDB and JSB)Lone Star Paralysis Foundation(to GDB).
文摘We have previously shown the success of polyethylene glycol fusion repair of segmental-loss peripheral nerve injuries in rats using freshly harvested,viable peripheral nerve allografts that can conduct action potentials.Because clinical application of polyethylene glycol fusion with viable peripheral nerve allografts demands pre-transplant donor tissue storage,we developed a protocol for ex vivo storage of rat sciatic nerves as viable peripheral nerve allografts,preserving many axons for up to 5 days.The current study evaluated the in vivo use of these stored viable peripheral nerve allografts.We hypothesized that stored viable peripheral nerve allografts with viable axons would enable successful in vivo repair of segmental-loss peripheral nerve injuries via polyethylene glycol-fusion.Polyethylene glycol-fused viable peripheral nerve allografts were classified as successful if they produced significantly improved locomotor recovery,as evaluated by the sciatic functional index,within 8 weeks post-repair.Many Sprague-Dawley and Lewis rats with successfully polyethylene glycol-fused viable peripheral nerve allografts had significantly improved sciatic functional index scores beginning at 5 weeks post-operatively.There was no significant difference in the efficiency and extent of successful polyethylene glycol fusion between stored and freshly harvested viable peripheral nerve allografts.In contrast,rats with non-fused negative control viable peripheral nerve allografts showed no recovery by 8 weeks post-operatively.Additional confirmatory outcome measures included in vivo compound action potentials and assessments of axon morphometry.These results suggest that viable peripheral nerve allografts can be stored and later used for successful polyethylene glycol fusion repair of segmental-loss peripheral nerve injuries.
基金supported by the National Key R&D Program of China,No.2022YFC3006200(to YW)the Natural Science Foundation of Beijing,No.7232190(to YW)+1 种基金Zhejiang Province Medical and Health Technology Plan Project,Nos.2022020506(to XW),2024KY1612(to JX),2024KY1615(to MY)Ningbo Clinical Research Center for Orthopedics and Sports Rehabilitation,No.2024L004(to XW).
文摘Peripheral nerve injury is a complex condition presenting significant clinical treatment challenges due to the limited regenerative capacity of peripheral nerves.Nerve conduits have been seen as a promising strategy to overcome the shortage of other treatment options(e.g.,nerve graft).However,nerve regeneration occurs within a complex environment,and elaborate modulation is needed to meet repair requirements.The aim of this study was to investigate and explore a multifunctional nerve conduit with reactive oxygen species clearing,immune modulation to reshape the regenerative environment,and topographic cues and electrical signals to guide nerve growth.We developed an electroactive nerve guidance conduit composed of polylactic-glycolic acid and carbon nanotubes with an oriented structure using electrospinning and modified it with mussel-inspired polydopamine combining neurotrophin-3.The resulting nerve scaffold exhibited favorable orientation,electrical conductivity,and mechanical properties.Continuous release of neurotrophin-3 from the nerve conduit supported nerve regeneration throughout the repair process.In vitro assessments confirmed the cytocompatibility,reactive oxygen species scavenging,and immune regulation capabilities of the nerve scaffolds.In a rat sciatic nerve defect model,the nerve scaffolds effectively prevented muscle atrophy and promoted nerve regeneration and functional recovery over a 12-week period.These findings suggest that polydopamine-modified,electroactive,oriented nerve guidance conduits with multiple bioactive functions hold great promise for the repair of peripheral nerve injuries.
基金supported by grants from the National Natural Science Foundation of China(No.82372382,82002333,32371412,and 32071349)the Central Guidance on Local Science and Technology Development Fund of Zhejiang Province(No.2024ZY01033)+1 种基金the Zhejiang Provincial Natural Science Foundation of China(No.LY24C100001)the Key Research and Development Program of Zhejiang(No.2022C01076).
文摘Bone is highly innervated,and its regeneration is significantly nerve-dependent.Extensive evidence suggests that the nervous system plays an active role in bone metabolism and development by modulating osteoblast and osteoclast activity.However,the majority of research to date has focused on the direct effects of peripheral nerves and their neurotransmitters on bone regeneration.Emerging studies have begun to reveal a more intricate role of nerves in regulating the immune microenvironment,which is crucial for bone regeneration.This review summarizes how nerves influence bone regeneration through modulation of the immune microenvironment.We first discuss the changes in peripheral nerves during the regenerative process.We then describe conduction and paracrine pathways through which nerves affect the osteogenic immune microenvironment,emphasizing nerves,neural factors,and their impacts.Our goal is to deepen the understanding of the nerve-immune axis in bone regeneration.A better grasp of how nerves influence the osteogenic immune microenvironment may lead to new strategies that integrate the nervous,immune,and skeletal systems to promote bone regeneration.
基金supported by the Shenzhen Hong Kong Joint Funding Project,No.SGDX20230116093645007(to LY)the Shenzhen Science and Technology Innovation Committee International Cooperation Project,No.GJHZ20200731095608025(to LY)+7 种基金Shenzhen Development and Reform Commission’s Intelligent Diagnosis,Treatment and Prevention of Adolescent Spinal Health Public Service Platform,No.S2002Q84500835(to LY)Shenzhen Medical Research Fund,No.B2303005(to LY)Team-based Medical Science Research Program,No.2024YZZ02(to LY)Zhejiang Provincial Natural Science Foundation of China,No.LWQ20H170001(to RL)Basic Research Project of Shenzhen Science and Technology from Shenzhen Science and Technology Innovation Commission,No.JCYJ20210324103010029(to BY)Shenzhen Second People’s Hospital Clinical Research Fund of Guangdong Province High-level Hospital Construction Project,Nos.2023yjlcyj029(to BY),2023yjlcyj021(to LL)Guangdong Basic and Applied Basic Research Foundation,No.2022A1515110679(to LL)China Postdoctoral Science Foundation,No.2022M722203(to GL).
文摘Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity,highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury;however,its role in modulating neuroinflammation post-peripheral nerve injury remains unknown.Here,we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms.Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel,we evaluated structural and functional recovery,macrophage phenotype alteration,specific cytokine expression,and changes in related signaling molecules in vivo.Similar parameters were evaluated in vitro using monocyte/macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel-coated plates in complete medium.These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages.Additionally,porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro.Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway,providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.
基金the support from Base for Interdisciplinary Innovative Talent Training,Shanghai Jiao Tong UniversityYouth Science and Technology Innovation Studio of Shanghai Jiao Tong University School of Medicine。
文摘Neural injuries can cause considerable functional impairments,and both central and peripheral nervous systems have limited regenerative capacity.The existing conventional pharmacological treatments in clinical practice show poor targeting,rapid drug clearance from the circulatory system,and low therapeutic efficiency.Therefore,in this review,we have first described the mechanisms underlying nerve regeneration,characterized the biomaterials used for drug delivery to facilitate nerve regeneration,and highlighted the functionalization strategies used for such drug-delivery systems.These systems mainly use natural and synthetic polymers,inorganic materials,and hybrid systems with advanced drug-delivery abilities,including nanoparticles,hydrogels,and scaffoldbased systems.Then,we focused on comparing the types of drug-delivery systems for neural regeneration as well as the mechanisms and challenges associated with targeted delivery of drugs to facilitate neural regeneration.Finally,we have summarized the clinical application research and limitations of targeted delivery of these drugs.These biomaterials and drug-delivery systems can provide mechanical support,sustained release of bioactive molecules,and enhanced intercellular contact,ultimately reducing cell apoptosis and enhancing functional recovery.Nevertheless,immune reactions,degradation regulation,and clinical translations remain major unresolved challenges.Future studies should focus on optimizing biomaterial properties,refining delivery precision,and overcoming translational barriers to advance these technologies toward clinical applications.
基金supported by the National Natural Science Foundation of China,Nos.82471123,82171053the Jilin Province Special Project for Talent in Medical and Health Sciences,No.2024WSXK-E01the Natural Science Foundation of Jilin Province,YDZJ202501ZYTS318(all to GL).
文摘Retinal ganglion cells,a crucial component of the central nervous system,are often affected by irreversible visual impairment due to various conditions,including trauma,tumors,ischemia,and glaucoma.Studies have shown that the optic nerve crush model and glaucoma model are commonly used to study retinal ganglion cell injury.While these models differ in their mechanisms,both ultimately result in retinal ganglion cell injury.With advancements in high-throughput technologies,techniques such as microarray analysis,RNA sequencing,and single-cell RNA sequencing have been widely applied to characterize the transcriptomic profiles of retinal ganglion cell injury,revealing underlying molecular mechanisms.This review focuses on optic nerve crush and glaucoma models,elucidating the mechanisms of optic nerve injury and neuron degeneration induced by glaucoma through single-cell transcriptomics,transcriptome analysis,and chip analysis.Research using the optic nerve crush model has shown that different retinal ganglion cell subtypes exhibit varying survival and regenerative capacities following injury.Single-cell RNA sequencing has identified multiple genes associated with retinal ganglion cell protection and regeneration,such as Gal,Ucn,and Anxa2.In glaucoma models,high-throughput sequencing has revealed transcriptomic changes in retinal ganglion cells under elevated intraocular pressure,identifying genes related to immune response,oxidative stress,and apoptosis.These genes are significantly upregulated early after optic nerve injury and may play key roles in neuroprotection and axon regeneration.Additionally,CRISPR-Cas9 screening and ATAC-seq analysis have identified key transcription factors that regulate retinal ganglion cell survival and axon regeneration,offering new potential targets for neurorepair strategies in glaucoma.In summary,single-cell transcriptomic technologies provide unprecedented insights into the molecular mechanisms underlying optic nerve injury,aiding in the identification of novel therapeutic targets.Future researchers should integrate advanced single-cell sequencing with multi-omics approaches to investigate cell-specific responses in retinal ganglion cell injury and regeneration.Furthermore,computational models and systems biology methods could help predict molecular pathways interactions,providing valuable guidance for clinical research on optic nerve regeneration and repair.
基金National Natural Science Foundation of China,No.82471412Science&Technology Innovation Talents Project of Henan Educational Committee,No.25HASTIT059+2 种基金Henan Academy of Medical Sciences Clinical Scientist Program,No.S20240069Young and Middle-aged Health Science and Technology Innovation Talent of Henan Province,No.JQRC2024014Henan Provincial Science&Technology Research and Development Program Joint Fund,No.232301420063(all to NZ)。
文摘Autologous nerve transplantation is currently recognized as the gold standard for treating seve re peripheral nerve injuries in clinical practice.Howeve r,challenges such as a limited supply of donors,complications in the donor area,and the formation of neuromas necessitate the optimization of existing transplantation strategies.Additionally,the development of new and promising repair methods is a critical issue in the field of peripheral nerve research.The purpose of this article is to compare the advantages and disadvantages of autologous,allogeneic,decellularized nerve grafts,and cell-composite graft,as well as to summarize the diffe rences in their prognostic factors and associated adve rse events.The length,diamete r,polarity,and sensory or motor origin of autografts all influence axonal regeneration.While pre-denaturation treatment can accele rate early regeneration,long-term functional outcomes of autografts do not show significant differences compared with fresh autologous grafts.For decellularized nerve grafts,defect length is identified as an independent risk factor,and the internal microenvironment(delayed angiogenesis,Schwann cell senescence,and reduced T-cell infiltration)is considered a key factor limiting long-segment regeneration.Additionally,the decellula rization process(whether chemical,physical,or supercritical CO_(2))affects the integrity of the extracellular matrix and the presence of immune residuals,which directly impacts axonal guidance and host integration.Common adve rse events following autograft transplantation include donor site numbness,neuromas,and scarring.In contrast,adverse events associated with decellularized nerve graft transplantation may present as inflammatory reactions,excessive scar prolife ration,and misalignment or reconnection of regenerating axons,which can lead to sensory-m otor cross-innervation.To mitigate these issues,combining decellularized nerve grafts with autologous Schwann cells,mesenchymal stem cells,or induced pluripotent stem cellderived cells may help bridge the gap with autografts.However,the fact that structural recovery does not necessarily lead to functional recovery needs further clarification.Future research should establish la rge animal models to replicate the limits of human regenerative capacity,use gene editing to enhance the phenotype and microenvironment of transplanted cells,and develop a mild combined decellularization process that maximizes the preservation of natural nerve grafts.Through multidimensional optimization,decellularized nerve grafts have the potential to ultimately re place autograft transplantation,enabling precise repair of individualized,long-segment,and complex nerve defects.
文摘Traumatic axonal lesions of peripheral nerves disrupt neuronal connections with their targets,resulting in the loss of motor and sensory functions.Despite the peripheral nervous system’s capacity for axonal regrowth,this may lead to permanent impairements resulting in a loss of quality of life and a high socioeconomic burden.
基金National Natural Science Foundation of China,No.32130060,No.81901256Jiangsu College Students Innovation and En trepreneurship Training Program,No.202310304120Y,No.202313993004Y2024 Medical Research Project by the Jiangsu Commission of Health,No.M2024009。
文摘Traditional nerve repair methods,such as autologous nerve grafting and allogeneic nerve grafting,face issues such as donor shortage,functional loss,and immune rejection.Decellularized extracellular matrix-based grafts have emerged as highly promising alternatives,capable of uniquely recreating the natural neural mic roenvironment,promoting host cell remodeling,and ultimately enhancing functional neural regeneration.This review comprehensively analyzes the key mechanisms of peripheral nerve injury and regeneration,focusing on contemporary therapeutic strategies for key aspects such as axonal apoptosis inhibition,enhanced intrinsic regenerative capacity,construction of regenerative microenvironment,and prevention of target organ atrophy.Findings from this review has shown that decellularized extra cellular matrix grafts can promote the migration,prolife ration,and differentiation of nerve cells by providing physical suppo rt,chemical signals,and mechanical stability.Decellularized extracellular matrix grafts are mainly used as ne rve conduits,scaffolds,hydrogels,and3D printing inks.Decellularized extra cellular matrix grafts have demonstrated significant advantages in promoting nerve regeneration by regulating the prolife ration and differentiation of Schwann cells,improving the neural microenvironment,reducing inflammato ry responses,and promoting angiogenesis.Additionally,decellularized extracellular matrix grafts can se rve as drug carrie rs,enabling the controlled release of growth factors,which further enhances nerve regeneration.However,these grafts also have some limitations,including the presence of immunogenic residues,inadequate mechanical prope rties,inter-batch variability,and uncontrollable degradation rates.Future research should focus on optimizing the decellularization process,enhancing the mechanical prope rties of decellularized extracellular matrix grafts,reducing immunogenicity,improving biocompatibility and safety,and developing new composite mate rials.Furthermore,exploring their application potential in complex nerve injuries,such as diabetic neuropathy,is crucial to meet the needs of peripheral nerve regeneration and repair.
基金supported by grants from Young Scientists Fund of the National Natural Science Foundation of China(grant number.82301295).
文摘1Introduction A 25-year-old woman presented with a 3-month history of otalgia and aural fullness in the left ear,without associated otological or systemic symptoms.Her medical history was unremarkable,and she denied any history of hepatitis,hypertension,diabetes,cardiovascular disease,or other significant conditions.The patient was diagnosed with external auditory canal cholesteatoma and subsequently underwent canalplasty under general anesthesia.Routine anesthetic drugs,including 2%lidocaine,dexamethasone,propofol,sufentanil,rocuronium bromide,ondansetron,flurbiprofen axetil,neostigmine,and atropine,were used during surgery and anesthesia recovery.No significant events were noted,and the patient experienced only a blood loss of 10 mL.
基金supported by the National Natural Science Foundation of China,No.32171356(to YW)Self-Support Research Projects of Shihezi University,No.ZZZC2021105(to WJ)+1 种基金Capital Medical University Natural Science Cultivation Fund,No.PYZ23044(to FQM)Beijing Municipal Natural Science Foundation,No.7244410(to JHD)。
文摘Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells.However,adult tissue–derived mesenchymal stem cells encounter various obstacles,including limited tissue sources,invasive acquisition methods,cellular heterogeneity,purification challenges,cellular senescence,and diminished pluripotency and proliferation over successive passages.In this study,we used induced pluripotent stem cell-derived mesenchymal stem cells,known for their self-renewal capacity,multilineage differentiation potential,and immunomodulatory characteristics.We used induced pluripotent stem cell-derived mesenchymal stem cells in conjunction with acellular nerve allografts to address a 10 mm-long defect in a rat model of sciatic nerve injury.Our findings reveal that induced pluripotent stem cell-derived mesenchymal stem cells exhibit survival for up to 17 days in a rat model of peripheral nerve injury with acellular nerve allograft transplantation.Furthermore,the combination of acellular nerve allograft and induced pluripotent stem cell-derived mesenchymal stem cells significantly accelerates the regeneration of injured axons and improves behavioral function recovery in rats.Additionally,our in vivo and in vitro experiments indicate that induced pluripotent stem cell-derived mesenchymal stem cells play a pivotal role in promoting neovascularization.Collectively,our results suggest the potential of acellular nerve allografts with induced pluripotent stem cell-derived mesenchymal stem cells to augment nerve regeneration in rats,offering promising therapeutic strategies for clinical translation.
基金National Natural Science Foundation of China(Grant No.52525504)Emerging Frontiers Cultivation Program of Tianjin University Interdisciplinary Center.
文摘Tactile feedback is critical for human interaction with external information.Similarly,tactile feedback can enrich the user's sensations when using prosthesis.To explore a potential scheme for tactile feedback,this study applied a non-inva-sive Transcutaneous Electrical Nerve Stimulation(TENS)to elicit tactile sensations in the hand,which involved median nerve,ulnar nerve,and radial nerve.Ten able-bodied subjects(8 males,2 females)were recruited to participate in the study.An array of 4×2 electrodes was positioned on the medial aspect of the brachii muscle's short head in the upper arm,which is in proximity to the median nerve,ulnar nerve,and radial nerve.Different electrode pairs were randomly selected to elicit distinct sensations at various positions on the hand,and the subjects reported the sensory areas.Then,the sensory areas and sensory thresholds were confirmed through psychophysical methods.According to the experimental results,tactile sensations were elicited at different locations on the subjects'hand through TENS of different electrode pairs.All subjects reported extensive and detailed sensory areas in the fingers,palm,and dorsum,corresponding to the sensory innervation areas of different nerves.The study effectively demonstrated the ability of TENS in evoking tactile feedback in the hand,paving the way for future optimization and development of prosthetic hands.
文摘Dear Editor,Dorsal pontine lesions may cause a variety of complex neuro-ophthalmic deficits,including horizontal gaze palsy(HGP),internuclear ophthalmoplegia,one-and-ahalf syndrome,abducens nerve palsy,skew deviation,or any combination of these.Here we present a rare case of an adult patient who developed multiple complicated clinical manifestations after surgical removal of a pontine cavernous hemangioma(PCH).Our case highlights a single pontine lesion may involve complicated neural pathways and result in complicated symptoms and signs,in which abducens nerve palsy or skew deviation is easily missed when combined with HGP.
基金Outstanding Young Investigator Program of Capital Medical University,Grant/Award Number:A2308。
文摘Phrenic nerve stimulation(PNS)may preserve diaphragm activation and mitigate multiorgan injury during mechanical ventilation(MV);however,a minimal invasive rat model integrating PNS with MV is lacking.We established an omohyoid muscle-based PNS rat model combined with MV.Bilateral nerves were exposed within 20±2 min by transection at the intermediate tendon of omohyoid muscle,minimizing trauma and bleeding.Threshold stimulation(0.6±0.2 mA)correlated with body weight.Ventilator-synchronized stimulation increased compound muscle action potentials by~30%,whereas histology confirmed intact nerve.Physiological parameters remained stable throughout ventilation.This model provides a safe and scalable platform for mechanistic and preclinical studies on PNS-mediated protection against MV-induced organ injury.
