Neuropathic pain(NP)is one of the most common pathological pain types and is associated with limited treatment options;moreover,it affects patients’quality of life and causes a heavy social burden.Despite the emphasi...Neuropathic pain(NP)is one of the most common pathological pain types and is associated with limited treatment options;moreover,it affects patients’quality of life and causes a heavy social burden.Despite the emphasis on inhibiting neuronal apoptosis to relieve NP,the crucial role of a neuroinflammation is often overlooked.Therefore,refocusing on the regulation of microglia polarization to create a more conducive environment for neuron holds great potential in NP treatment.In recent years,small interfering RNAs(siRNAs)had become an attractive therapeutic option.However,an efficient loading and delivery system for siRNA is still in lack.In our study,a nanostructured tetrahedral framework nucleic acid loaded with the small interfering RNA C–C chemokine receptor 2(T-siCCR2)was successfully designed and synthesized for use in NP rat model in vivo and in a lipopolysaccharide(LPS)-induced inflammatory environment in vitro.This nanoscale complex is endowed with structural stability and satisfactory delivery efficiency while assuring the silencing effect of siRNA-CCR2.In vivo,T-siCCR2 treatment exhibited favorable effects on pain relief and functional improvement in the NP animal model by directly targeting microglia.In vitro,T-siCCR2 counteracts LPS-induced inflammation by inhibiting the differentiation of microglia toward the M1 phenotype,thus playing a neuroprotective role.RNA sequencing was subsequently performed to elucidate the underlying mechanism involved.These results indicate that T-siCCR2 may serve as a potential treatment option for NP in the future.展开更多
Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic ...Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.展开更多
Photothermal therapy(PTT)is a desirable way to attain on-demand hyperthermia owing to the heat gen-erated by photothermal materials absorbing near-infrared light.The mild heat(42±0.5℃)can not only accelerate bon...Photothermal therapy(PTT)is a desirable way to attain on-demand hyperthermia owing to the heat gen-erated by photothermal materials absorbing near-infrared light.The mild heat(42±0.5℃)can not only accelerate bone tissue regeneration but also promote the release of bioactive ions from biomaterials.Based on this one-stone-two-birds strategy,a 3D printed PEEK-graphene composite scaffold(PG)with hydroxyapatite(HA)coating(PGH)for photothermally remote control of bone regeneration was well de-signed in this study.The results showed that the HA coating on PGH could release Ca^(2+)and PO_(4)^(3-)ions easily under NIR irradiation,which was ascribed to the mild heat generated from graphene in the com-posite scaffold.The mild heat and the boosted Ca^(2+)/PO_(4)^(3-)release could synergistically enhance the bone regeneration ability both in vitro and in vivo.The underlying mechanism was further explored and con-firmed to be closely related to the upregulation of HSP 70,by which the MAPK/ERK signaling pathway was activated selectively.The favorable results demonstrate that the 3D-printed PEEK/graphene composite scaffold is promising in the applications of bone defect repair.展开更多
Chondrocytes and osteoblasts differentiate from a common mesenchymal precursor, the osteochondroprogenitor（OCP）, and help build the vertebrate skeleton. The signaling pathways that control lineage commitment for OCP...Chondrocytes and osteoblasts differentiate from a common mesenchymal precursor, the osteochondroprogenitor（OCP）, and help build the vertebrate skeleton. The signaling pathways that control lineage commitment for OCPs are incompletely understood. We asked whether the ubiquitously expressed protein-tyrosine phosphatase SHP2（encoded by Ptpn11） affects skeletal lineage commitment by conditionally deleting Ptpn11 in mouse limb and head mesenchyme using ＂Cre-lox P＂-mediated gene excision.SHP2-deficient mice have increased cartilage mass and deficient ossification, suggesting that SHP2-deficient OCPs become chondrocytes and not osteoblasts. Consistent with these observations, the expression of the master chondrogenic transcription factor SOX9 and its target genes Acan, Col2a1, and Col10a1 were increased in SHP2-deficient chondrocytes, as revealed by gene expression arrays, q RT-PCR, in situ hybridization, and immunostaining. Mechanistic studies demonstrate that SHP2 regulates OCP fate determination via the phosphorylation and SUMOylation of SOX9, mediated at least in part via the PKA signaling pathway. Our data indicate that SHP2 is critical for skeletal cell lineage differentiation and could thus be a pharmacologic target for bone and cartilage regeneration.展开更多
Chondroitin sulfate proteoglycans （CSPGs） which are produced by mature oligodendrocytes and reactive astrocytes can be upregulated after spinal cord injury and contribute to regenerative failure. Chondroitinase ABC ...Chondroitin sulfate proteoglycans （CSPGs） which are produced by mature oligodendrocytes and reactive astrocytes can be upregulated after spinal cord injury and contribute to regenerative failure. Chondroitinase ABC （ChABC） digests glycosaminoglycan chains on CSPGs and can thereby overcome CSPG-mediated inhibition. However, many current studies have used an incomplete spinal cord injury model, and examined results after 8-12 weeks of ChABC treatment. In this study, a complete rat spinal cord transection injury model was used to study the long-term effects of ChABC treatment by subarachnoid catheter. Pathology of spinal cord regeneration was compared with control 24 weeks following ChABC treatment using immunohistochemistry and axon tracing techniques. At 24 weeks after injury, neurofilament 200 expression was significantly greater in the ChABC treatment group compared with the transection group. In the ChABC treatment group, axonal growth was demonstrated by a large number of biotinylated dextran amine positive axons caudal to, or past, the epicenter of injury. Biotinylated dextran amine-labeled fibers were found in the proximal end of the spinal cord in the transection alone group. These results confirm that ChABC can promote axon growth, neural regeneration, and repair after spinal cord injury in rats long after the initial injury.展开更多
BACKGROUND： Nogo A antigen is the major inhibiting factor blocking regeneration of the injured spinal cord. Neutralizing Nogo A antigens using Nogo A antibodies may help promote neurite regeneration and nervous funct...BACKGROUND： Nogo A antigen is the major inhibiting factor blocking regeneration of the injured spinal cord. Neutralizing Nogo A antigens using Nogo A antibodies may help promote neurite regeneration and nervous function recovery. For successful regeneration, sustained release of the antibody from a biodegradable material loaded with Nogo A antibodies to the injury site is required. OBJECTIVE： To compare the therapeutic effects of poly lactic-co-glycolic acid （PLGA）-Nogo A antibody delayed-release microspheres and Nogo A antibody alone on spinal regeneration in Sprague-Dawley rats with complete transverse injury to the spinal cord. DESIGN, TIME AND SETTING： A randomized, controlled animal trial was performed at the Pharmacological Laboratory of West China Center of Medical Sciences, Sichuan University, between October 2007 and January 2008. MATERIALS： Goat anti-rat Nogo A monoclonal antibody was purchased from Santa, American; goat anti-rat neurofilament 200 monoclonal antibody was from Zhongshan Goldenbridge, Beijing, China; PLGA-Nogo A antibody delayed-release microspheres were provided by the College of Pharmacy, Sichuan University. METHODS： A total of 36 adult female Sprague Dawley rats were used to establish models of completely transected spinal cord injury, at T10. Animals were randomly divided into three groups （n=12）： model, Nogo A antibody alone, and Nogo A antibody delayed-release microsphere groups. After transverse injury of the spinal cord, 50 μ L normal saline solution, 50 μL normal saline solution containing 50μL g Nogo A antibody, and 50 μL normal saline solution containing 50 μg Nogo A antibody microspheres were administered to the respective groups at the injury site. MAIN OUTCOME MEASURES： The expression of Nogo A and neurofilament 200 in injured spinal cord was tested immunohistochemically, and motor function of rats was assessed by Basso-Beattie-Bresnahan （BBB） locomotor rating scale. RESULTS： Four weeks after injury, expression of Nogo A in microsphere group was significantly less than model and Nogo A antibody alone groups （P 〈 0.05）; while there was no significant difference between model and Nogo A antibody alone groups （P 〉 0.05）. Ten weeks after injury, microsphere group showed a significantly greater expression of neurofilament 200 than model and Nogo A antibody alone groups （P 〈 0.05）; while no significant difference was found between model and Nogo A antibody alone groups （P 〉 0.05）. At postoperative weeks 5 and 6, the score of BBB locomotor rating scale in microsphere group was significantly greater than the model group （P 〈 0.05）, and at postoperative weeks 7 10, the score was much greater than model and Nogo A antibody alone groups （P 〈 0.05）. CONCLUSION： Nogo A antibody delayed-release microspheres decreased Nogo A expression, increased neurofilament 200 expression in the injured spinal cord of rats, and promoted recovery of motor function through sustained drug release over a long-term period.展开更多
The authors regret that in Fig.2Aa of the article,the images for TPUPPy and TPU-aa in the first column were mistakenly duplicated due to a formatting error.The correct version of Fig.2 is provided below,along with the...The authors regret that in Fig.2Aa of the article,the images for TPUPPy and TPU-aa in the first column were mistakenly duplicated due to a formatting error.The correct version of Fig.2 is provided below,along with the original data for reference.The authors confirm that the rest of the article remains unaffected.展开更多
Interbody fusion devices are critical in spinal surgery to restore spinal stability,reduce pain and improve function.Polyetheretherketone(PEEK)has become a commonly used alternative material for fusion cages owing to ...Interbody fusion devices are critical in spinal surgery to restore spinal stability,reduce pain and improve function.Polyetheretherketone(PEEK)has become a commonly used alternative material for fusion cages owing to its excellent mechanical properties and biocompatibility,but its biological inertness limits bone regeneration and may lead to poor fusion.In this study,a novel strategy for preparing bioactive biomineralized PEEK cages was developed using a unique combination of osteoinductive CaP bioceramic fillings in the cage window,acid sulfonation and simulated body fluid incubation.In vitro experiments showed that biomineralized PEEK cages and CaP bioceramics regulate immunity and promote angiogenesis and bone integration via activation of hypoxia-inducible factor 1-alpha and cyclic guanosine monophosphate/protein kinase G signaling pathways.In vivo goat spinal fusion experiments demonstrated that PEEK cages filled with CaP bioceramics resulted in good bone growth and spinal fusion.Therefore,the high mechanical strength and good biocompatibility of biomineralized PEEK cages,together with the excellent bioactivity and degradation properties of CaP bioceramics,provide an ideal microenvironment for bone fusion.The development of this composite material not only addresses some of the limitations of existing fusion devices but also will facilitate the development of spinal fusion technology.展开更多
Previous studies have confirmed that intervertebral disc degeneration(IDD)is closely associated with inflammation-induced reactive oxygen species(ROS)and resultant cell mitochondrial membrane potential(MMP)decline.Cle...Previous studies have confirmed that intervertebral disc degeneration(IDD)is closely associated with inflammation-induced reactive oxygen species(ROS)and resultant cell mitochondrial membrane potential(MMP)decline.Clearance of ROS in an inflammatory environment is essential for breaking the vicious cycle of MMP decline.Additionally,re-energizing the mitochondria damaged in the inflammatory milieu to restore their function,is equally important.Herein,we proposed an interesting concept of mitochondrion-engine equipped with coolant,which enables first to“cool-down”the inflammatory environment,next to restore the MMP,finally to allow cells to regain normal energy metabolism through materials design.As such,we developed a multifunctional composite composed of a reactive oxygen species(ROS)-responsive sodium alginate/gelatin hydrogel infused into a rigid 3D-printed thermoplastic polyurethane(TPU)scaffold.The TPU scaffold was coated with conductive polypyrrole(PPy)to electrophoretically deposit L-arginine,which could upregulate the Mammalian target of rapamycin(mTOR)pathway,thus increasing MMP and energy metabolism to stimulate extracellular matrix synthesis for IVD repair.While the ROS-responsive hydrogel acting as the“mito-engine coolant”could scavenge the excessive ROS to create a favorable environment for IVD cells recovery.Demonstrated by in vitro and in vivo evaluations,the mito-engine system markedly promoted the proliferation and collagen synthesis of nucleus pulposus cells while enhancing the mitochondrial respiration and MMP under oxidative stress.Radiological and histological assessments in vivo revealed the efficacy of this system in IVD repair.This unique bioinspired design integrated biomaterial science with mitochondrial biology,presents a promising paradigm for IDD treatment.展开更多
The authors regret that in Fig.2Aa of the article,the images for TPUPPy and TPU-aa in the first column were mistakenly duplicated due to a formatting error.The correct version of Fig.2 is provided below,along with the...The authors regret that in Fig.2Aa of the article,the images for TPUPPy and TPU-aa in the first column were mistakenly duplicated due to a formatting error.The correct version of Fig.2 is provided below,along with the original data for reference.The authors confirm that the rest of the article remains unaffected.展开更多
Osteoinductivity is a crucial factor to determine the success and efficiency of posterolateral spinal fusion(PLF)by employing calcium phosphate(Ca-P)bioceramics.In this study,three kinds of Ca-P ceramics with microsca...Osteoinductivity is a crucial factor to determine the success and efficiency of posterolateral spinal fusion(PLF)by employing calcium phosphate(Ca-P)bioceramics.In this study,three kinds of Ca-P ceramics with microscale to nanoscale gain size(BCP-control,BCP-micro and BCP-nano)were prepared and their physicochemical properties were characterized.BCP-nano had the spherical shape and nanoscale gain size,BCP-micro had the spherical shape and microscale gain size,and BCP-control(BAM®)had the irregular shape and microscale gain size.The obtained BCP-nano with specific nanotopography could well regulate in vitro protein adsorption and osteogenic differentiation of MC3T3 cells.In vivo rabbit PLF procedures further confirmed that nanotopography of BCP-nano might be responsible for the stronger bone regenerative ability comparing with BCP-micro and BCP-control.Collectedly,due to nanocrystal similarity with natural bone apatite,BCP-nano has excellent efficacy in guiding bone regeneration of PLF,and holds great potentials to become an alternative to standard bone grafts for future clinical applications.展开更多
To the Editor:There is a high probability of requiring unplanned surgery for congenital scoliosis(CS),but very few publications have reported the proportion of unplanned surgeries,the causes of those unplanned surgeri...To the Editor:There is a high probability of requiring unplanned surgery for congenital scoliosis(CS),but very few publications have reported the proportion of unplanned surgeries,the causes of those unplanned surgeries,and the prevalence of each cause.This study aimed to provide more information regarding the above.We reviewed the electronic medical records of patients with CS that underwent unplanned surgeries at our hospital from 2009 to 2018.By searching the database of West China Hospital,we found 317 CS cases.Of these,33 cases underwent unplanned surgeries,of which five had their primary surgeries at outside hospitals.The unplanned surgery rate in our case series was 9.0%(28/312).In our case series,the most common cause of unplanned surgery for patients with CS was progressive deformity(49%,16/33),followed by implant-related complications(36%,12/33),wound-related complications(12%,4/33),and surgical error-related complications(cerebrospinal fluid[CSF]leak,3%,1/33).The most common reason for unplanned surgery in CS was progressive spinal deformity or imbalance,which accounted for 49%(16/33)of the unplanned surgeries.展开更多
基金supported by National Natural Science Foundation of China(Nos.81874027,82370929,81970916)Sichuan Science and Technology Program(Nos.2019YFQ0003,2022YFS0051,2022NSFSC0002)+3 种基金Sichuan Province Youth Science and Technology Innovation Team(No.2022JDTD0021)Research and Develop Program,West China Hospital of Stomatology Sichuan University(Nos.RD03202302,RCDWJS2024–1)135-project for disciplines of excellenceClinical Research Incubation project of West China Hospital of Sichuan University(No.2021HXFH036)。
文摘Neuropathic pain(NP)is one of the most common pathological pain types and is associated with limited treatment options;moreover,it affects patients’quality of life and causes a heavy social burden.Despite the emphasis on inhibiting neuronal apoptosis to relieve NP,the crucial role of a neuroinflammation is often overlooked.Therefore,refocusing on the regulation of microglia polarization to create a more conducive environment for neuron holds great potential in NP treatment.In recent years,small interfering RNAs(siRNAs)had become an attractive therapeutic option.However,an efficient loading and delivery system for siRNA is still in lack.In our study,a nanostructured tetrahedral framework nucleic acid loaded with the small interfering RNA C–C chemokine receptor 2(T-siCCR2)was successfully designed and synthesized for use in NP rat model in vivo and in a lipopolysaccharide(LPS)-induced inflammatory environment in vitro.This nanoscale complex is endowed with structural stability and satisfactory delivery efficiency while assuring the silencing effect of siRNA-CCR2.In vivo,T-siCCR2 treatment exhibited favorable effects on pain relief and functional improvement in the NP animal model by directly targeting microglia.In vitro,T-siCCR2 counteracts LPS-induced inflammation by inhibiting the differentiation of microglia toward the M1 phenotype,thus playing a neuroprotective role.RNA sequencing was subsequently performed to elucidate the underlying mechanism involved.These results indicate that T-siCCR2 may serve as a potential treatment option for NP in the future.
基金supported by the National Key Research and Development Project,No.2019YFA0112100(to SF).
文摘Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.
基金supported by grants from the Project funded by the China Postdoctoral Science Foundation(Nos.2023M732469 and 2023M732477)the Sichuan University Postdoctoral Interdisciplinary Innovation Fund(No.JCXK2205)+3 种基金the Projects of the Science and Technology Department of Sichuan Province(Nos.24NSFSC7945,24NSFSC6493,2022ZDZX0029,2023NSFSC0659,MZGC20230019)the National Natural Science Foundation of China(No.52302351)the Sichuan Provincial Medical Association Special Research Fund(Nos.2021SAT05 and 2019HR18)the National Program for Postdoctoral Researchers(No.GZB20230485)as well as the Fundamental Research Funds for the Central Universities(No.2023SCU12116).
文摘Photothermal therapy(PTT)is a desirable way to attain on-demand hyperthermia owing to the heat gen-erated by photothermal materials absorbing near-infrared light.The mild heat(42±0.5℃)can not only accelerate bone tissue regeneration but also promote the release of bioactive ions from biomaterials.Based on this one-stone-two-birds strategy,a 3D printed PEEK-graphene composite scaffold(PG)with hydroxyapatite(HA)coating(PGH)for photothermally remote control of bone regeneration was well de-signed in this study.The results showed that the HA coating on PGH could release Ca^(2+)and PO_(4)^(3-)ions easily under NIR irradiation,which was ascribed to the mild heat generated from graphene in the com-posite scaffold.The mild heat and the boosted Ca^(2+)/PO_(4)^(3-)release could synergistically enhance the bone regeneration ability both in vitro and in vivo.The underlying mechanism was further explored and con-firmed to be closely related to the upregulation of HSP 70,by which the MAPK/ERK signaling pathway was activated selectively.The favorable results demonstrate that the 3D-printed PEEK/graphene composite scaffold is promising in the applications of bone defect repair.
基金supported by NIH R21AR57156NIH R37 CA49152+4 种基金the Rhode Island Hospital Orthopaedic Foundationgrant from the Pediatric Orthopaedic Society of North AmericaArthritis National Research Foundationrecipient of Ryan Fellowshippilot award recipient from NIGMS1P20 GM119943
文摘Chondrocytes and osteoblasts differentiate from a common mesenchymal precursor, the osteochondroprogenitor（OCP）, and help build the vertebrate skeleton. The signaling pathways that control lineage commitment for OCPs are incompletely understood. We asked whether the ubiquitously expressed protein-tyrosine phosphatase SHP2（encoded by Ptpn11） affects skeletal lineage commitment by conditionally deleting Ptpn11 in mouse limb and head mesenchyme using ＂Cre-lox P＂-mediated gene excision.SHP2-deficient mice have increased cartilage mass and deficient ossification, suggesting that SHP2-deficient OCPs become chondrocytes and not osteoblasts. Consistent with these observations, the expression of the master chondrogenic transcription factor SOX9 and its target genes Acan, Col2a1, and Col10a1 were increased in SHP2-deficient chondrocytes, as revealed by gene expression arrays, q RT-PCR, in situ hybridization, and immunostaining. Mechanistic studies demonstrate that SHP2 regulates OCP fate determination via the phosphorylation and SUMOylation of SOX9, mediated at least in part via the PKA signaling pathway. Our data indicate that SHP2 is critical for skeletal cell lineage differentiation and could thus be a pharmacologic target for bone and cartilage regeneration.
基金the National Natural Science Foundation of China,No.30471759
文摘Chondroitin sulfate proteoglycans （CSPGs） which are produced by mature oligodendrocytes and reactive astrocytes can be upregulated after spinal cord injury and contribute to regenerative failure. Chondroitinase ABC （ChABC） digests glycosaminoglycan chains on CSPGs and can thereby overcome CSPG-mediated inhibition. However, many current studies have used an incomplete spinal cord injury model, and examined results after 8-12 weeks of ChABC treatment. In this study, a complete rat spinal cord transection injury model was used to study the long-term effects of ChABC treatment by subarachnoid catheter. Pathology of spinal cord regeneration was compared with control 24 weeks following ChABC treatment using immunohistochemistry and axon tracing techniques. At 24 weeks after injury, neurofilament 200 expression was significantly greater in the ChABC treatment group compared with the transection group. In the ChABC treatment group, axonal growth was demonstrated by a large number of biotinylated dextran amine positive axons caudal to, or past, the epicenter of injury. Biotinylated dextran amine-labeled fibers were found in the proximal end of the spinal cord in the transection alone group. These results confirm that ChABC can promote axon growth, neural regeneration, and repair after spinal cord injury in rats long after the initial injury.
基金the National Natural Science Foundation of China,No.30471759
文摘BACKGROUND： Nogo A antigen is the major inhibiting factor blocking regeneration of the injured spinal cord. Neutralizing Nogo A antigens using Nogo A antibodies may help promote neurite regeneration and nervous function recovery. For successful regeneration, sustained release of the antibody from a biodegradable material loaded with Nogo A antibodies to the injury site is required. OBJECTIVE： To compare the therapeutic effects of poly lactic-co-glycolic acid （PLGA）-Nogo A antibody delayed-release microspheres and Nogo A antibody alone on spinal regeneration in Sprague-Dawley rats with complete transverse injury to the spinal cord. DESIGN, TIME AND SETTING： A randomized, controlled animal trial was performed at the Pharmacological Laboratory of West China Center of Medical Sciences, Sichuan University, between October 2007 and January 2008. MATERIALS： Goat anti-rat Nogo A monoclonal antibody was purchased from Santa, American; goat anti-rat neurofilament 200 monoclonal antibody was from Zhongshan Goldenbridge, Beijing, China; PLGA-Nogo A antibody delayed-release microspheres were provided by the College of Pharmacy, Sichuan University. METHODS： A total of 36 adult female Sprague Dawley rats were used to establish models of completely transected spinal cord injury, at T10. Animals were randomly divided into three groups （n=12）： model, Nogo A antibody alone, and Nogo A antibody delayed-release microsphere groups. After transverse injury of the spinal cord, 50 μ L normal saline solution, 50 μL normal saline solution containing 50μL g Nogo A antibody, and 50 μL normal saline solution containing 50 μg Nogo A antibody microspheres were administered to the respective groups at the injury site. MAIN OUTCOME MEASURES： The expression of Nogo A and neurofilament 200 in injured spinal cord was tested immunohistochemically, and motor function of rats was assessed by Basso-Beattie-Bresnahan （BBB） locomotor rating scale. RESULTS： Four weeks after injury, expression of Nogo A in microsphere group was significantly less than model and Nogo A antibody alone groups （P 〈 0.05）; while there was no significant difference between model and Nogo A antibody alone groups （P 〉 0.05）. Ten weeks after injury, microsphere group showed a significantly greater expression of neurofilament 200 than model and Nogo A antibody alone groups （P 〈 0.05）; while no significant difference was found between model and Nogo A antibody alone groups （P 〉 0.05）. At postoperative weeks 5 and 6, the score of BBB locomotor rating scale in microsphere group was significantly greater than the model group （P 〈 0.05）, and at postoperative weeks 7 10, the score was much greater than model and Nogo A antibody alone groups （P 〈 0.05）. CONCLUSION： Nogo A antibody delayed-release microspheres decreased Nogo A expression, increased neurofilament 200 expression in the injured spinal cord of rats, and promoted recovery of motor function through sustained drug release over a long-term period.
文摘The authors regret that in Fig.2Aa of the article,the images for TPUPPy and TPU-aa in the first column were mistakenly duplicated due to a formatting error.The correct version of Fig.2 is provided below,along with the original data for reference.The authors confirm that the rest of the article remains unaffected.
基金sponsored by the National Natural Science Foundation of China(No.82072386,52372269)the Projects of the Science&Technology Department of Sichuan Province(No.24ZDYF0475,2022ZDZX0029)+1 种基金the Natural Science Foundation of Sichuan Province(No.2024NSFSC1808)the 1-3-5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYGD21001).
文摘Interbody fusion devices are critical in spinal surgery to restore spinal stability,reduce pain and improve function.Polyetheretherketone(PEEK)has become a commonly used alternative material for fusion cages owing to its excellent mechanical properties and biocompatibility,but its biological inertness limits bone regeneration and may lead to poor fusion.In this study,a novel strategy for preparing bioactive biomineralized PEEK cages was developed using a unique combination of osteoinductive CaP bioceramic fillings in the cage window,acid sulfonation and simulated body fluid incubation.In vitro experiments showed that biomineralized PEEK cages and CaP bioceramics regulate immunity and promote angiogenesis and bone integration via activation of hypoxia-inducible factor 1-alpha and cyclic guanosine monophosphate/protein kinase G signaling pathways.In vivo goat spinal fusion experiments demonstrated that PEEK cages filled with CaP bioceramics resulted in good bone growth and spinal fusion.Therefore,the high mechanical strength and good biocompatibility of biomineralized PEEK cages,together with the excellent bioactivity and degradation properties of CaP bioceramics,provide an ideal microenvironment for bone fusion.The development of this composite material not only addresses some of the limitations of existing fusion devices but also will facilitate the development of spinal fusion technology.
基金the National Natural Science Foundation of China(82172495,82260431,82072434,82372453)Project funded by China Postdoctoral Science Foundation(2023M732469)+2 种基金Sichuan University Postdoctoral Interdisciplinary Innovation Fund(JCXK2205)Projects of the Science and Technology Department of Sichuan Province(2022ZDZX0029,MZGC20230019)the 1⋅3⋅5 project for disciplines of excellence Clinical Research Incubation Project,West China Hospital,Sichuan University(2021HXFH003).
文摘Previous studies have confirmed that intervertebral disc degeneration(IDD)is closely associated with inflammation-induced reactive oxygen species(ROS)and resultant cell mitochondrial membrane potential(MMP)decline.Clearance of ROS in an inflammatory environment is essential for breaking the vicious cycle of MMP decline.Additionally,re-energizing the mitochondria damaged in the inflammatory milieu to restore their function,is equally important.Herein,we proposed an interesting concept of mitochondrion-engine equipped with coolant,which enables first to“cool-down”the inflammatory environment,next to restore the MMP,finally to allow cells to regain normal energy metabolism through materials design.As such,we developed a multifunctional composite composed of a reactive oxygen species(ROS)-responsive sodium alginate/gelatin hydrogel infused into a rigid 3D-printed thermoplastic polyurethane(TPU)scaffold.The TPU scaffold was coated with conductive polypyrrole(PPy)to electrophoretically deposit L-arginine,which could upregulate the Mammalian target of rapamycin(mTOR)pathway,thus increasing MMP and energy metabolism to stimulate extracellular matrix synthesis for IVD repair.While the ROS-responsive hydrogel acting as the“mito-engine coolant”could scavenge the excessive ROS to create a favorable environment for IVD cells recovery.Demonstrated by in vitro and in vivo evaluations,the mito-engine system markedly promoted the proliferation and collagen synthesis of nucleus pulposus cells while enhancing the mitochondrial respiration and MMP under oxidative stress.Radiological and histological assessments in vivo revealed the efficacy of this system in IVD repair.This unique bioinspired design integrated biomaterial science with mitochondrial biology,presents a promising paradigm for IDD treatment.
文摘The authors regret that in Fig.2Aa of the article,the images for TPUPPy and TPU-aa in the first column were mistakenly duplicated due to a formatting error.The correct version of Fig.2 is provided below,along with the original data for reference.The authors confirm that the rest of the article remains unaffected.
基金sponsored by the National Natural Science Foundation of China(52002256)Sichuan Science and Technology Innovation Team of China(2019JDTD0008)+2 种基金China Postdoctoral Innovation Talent Support program(BX20180204)China Postdoctoral Science Foundation(2018M643483)Sichuan University Postdoctoral Interdisciplinary Innovation Fund(0900904153024).
文摘Osteoinductivity is a crucial factor to determine the success and efficiency of posterolateral spinal fusion(PLF)by employing calcium phosphate(Ca-P)bioceramics.In this study,three kinds of Ca-P ceramics with microscale to nanoscale gain size(BCP-control,BCP-micro and BCP-nano)were prepared and their physicochemical properties were characterized.BCP-nano had the spherical shape and nanoscale gain size,BCP-micro had the spherical shape and microscale gain size,and BCP-control(BAM®)had the irregular shape and microscale gain size.The obtained BCP-nano with specific nanotopography could well regulate in vitro protein adsorption and osteogenic differentiation of MC3T3 cells.In vivo rabbit PLF procedures further confirmed that nanotopography of BCP-nano might be responsible for the stronger bone regenerative ability comparing with BCP-micro and BCP-control.Collectedly,due to nanocrystal similarity with natural bone apatite,BCP-nano has excellent efficacy in guiding bone regeneration of PLF,and holds great potentials to become an alternative to standard bone grafts for future clinical applications.
基金This work was supported by grants from the China Postdoctoral Science Foundation General Program(No.2019M653417)Sichuan Science and Technology Program(No.2020YJ0025)+1 种基金Post-Doctor Research Project,Sichuan University(No.2019SCU12043)International Postdoctoral Exchange Fellowship Program(No.PC2019060)。
文摘To the Editor:There is a high probability of requiring unplanned surgery for congenital scoliosis(CS),but very few publications have reported the proportion of unplanned surgeries,the causes of those unplanned surgeries,and the prevalence of each cause.This study aimed to provide more information regarding the above.We reviewed the electronic medical records of patients with CS that underwent unplanned surgeries at our hospital from 2009 to 2018.By searching the database of West China Hospital,we found 317 CS cases.Of these,33 cases underwent unplanned surgeries,of which five had their primary surgeries at outside hospitals.The unplanned surgery rate in our case series was 9.0%(28/312).In our case series,the most common cause of unplanned surgery for patients with CS was progressive deformity(49%,16/33),followed by implant-related complications(36%,12/33),wound-related complications(12%,4/33),and surgical error-related complications(cerebrospinal fluid[CSF]leak,3%,1/33).The most common reason for unplanned surgery in CS was progressive spinal deformity or imbalance,which accounted for 49%(16/33)of the unplanned surgeries.
