In vivo imaging of the neuronal response to spinal cord injury:a narrative review

Deciphering the neuronal response to injury in the spinal cord is essential for exploring treatment strategies for spinal cord injury(SCI).However,this subject has been neglected in part because appropriate tools are lacking.Emerging in vivo imaging and labeling methods offer great potential for observing dynamic neural processes in the central nervous system in conditions of health and disease.This review first discusses in vivo imaging of the mouse spinal cord with a focus on the latest imaging techniques,and then analyzes the dynamic biological response of spinal cord sensory and motor neurons to SCI.We then summarize and compare the techniques behind these studies and clarify the advantages of in vivo imaging compared with traditional neuroscience examinations.Finally,we identify the challenges and possible solutions for spinal cord neuron imaging.

A novel flexible nerve guidance conduit promotes nerve regeneration while providing excellent mechanical properties

Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor site.As an alternative,nerve guidance conduits may be used.The ideal conduit should be flexible,resistant to kinks and lumen collapse,and provide physical cues to guide nerve regeneration.We designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align them.Subsequently,we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber lumen.The presence of aligned fibers on the inner surface can promote the extension of nerve cells along the fibers.The helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide stability.Our novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model,suggesting that it has potential for clinical use in human nerve injuries.

Bench-to-bedside strategies for osteoporotic fracture: from osteoimmunology to mechanosensation

Osteoporosis is characterized by a decrease in bone mass and strength, rendering people prone to osteoporotic fractures caused by low-energy forces. The primary treatment strategy for osteoporotic fractures is surgery;however, the compromised and comminuted bones in osteoporotic fracture sites are not conducive to optimum reduction and rigid fixation. In addition, these patients always exhibit accompanying aging-related disorders, including high inflammatory status, decreased mechanical loading and abnormal skeletal metabolism, which are disadvantages for fracture healing around sites that have undergone orthopedic procedures. Since the incidence of osteoporosis is expected to increase worldwide, orthopedic surgeons should pay more attention to comprehensive strategies for improving the poor prognosis of osteoporotic fractures. Herein, we highlight the molecular basis of osteoimmunology and bone mechanosensation in different healing phases of elderly osteoporotic fractures, guiding perioperative management to alleviate the unfavorable effects of insufficient mechanical loading, high inflammatory levels and pathogen infection. The well-informed pharmacologic and surgical intervention, including treatment with anti-inflammatory drugs and sufficient application of antibiotics, as well as bench-to-bedside strategies for bone augmentation and hardware selection, should be made according to a comprehensive understanding of bone biomechanical properties in addition to the remodeling status of osteoporotic bones, which is necessary for creating proper biological and mechanical environments for bone union and remodeling. Multidisciplinary collaboration will facilitate the improvement of overall osteoporotic care and reduction of secondary fracture incidence.

Skeleton-vasculature chain reaction: a novel insight into the mystery of homeostasis

Angiogenesis and osteogenesis are coupled.However,the cellular and molecular regulation of these processes remains to be further investigated.Both tissues have recently been recognized as endocrine organs,which has stimulated research interest in the screening and functional identification of novel paracrine factors from both tissues.This review aims to elaborate on the novelty and significance of endocrine regulatory loops between bone and the vasculature.In addition,research progress related to the bone vasculature,vessel-related skeletal diseases,pathological conditions,and angiogenesis-targeted therapeutic strategies are also summarized.With respect to future perspectives,new techniques such as single-cell sequencing,which can be used to show the cellular diversity and plasticity of both tissues,are facilitating progress in this field.Moreover,extracellular vesicle-mediated nuclear acid communication deserves further investigation.In conclusion,a deeper understanding of the cellular and molecular regulation of angiogenesis and osteogenesis coupling may offer an opportunity to identify new therapeutic targets.

Green tea polyphenols protect spinal cord neurons against hydrogen peroxide-induced oxidative stress

Green tea polyphenols are strong antioxidants and can reduce free radical damage. To investigate their neuroprotective potential, we induced oxidative damage in spinal cord neurons using hydrogen peroxide, and applied different concentrations （50-200μg,/mL） of green tea polyphenol to the cell medium for 24 hours. Measurements of superoxide dismutase activity, malondialdehyde content, and expression of apoptosis-related genes and proteins revealed that green tea polyphenol effectively alleviated oxidative stress. Our results indicate that green tea polyphenols play a protective role in spinal cord neurons under oxidative stress.

The potential risks of C-C chemokine receptor 5-edited babies in bone development

Hutter et al.1 first reported that a bone marrow transplant using stem cells derived from a donor with homozygous CCR5 delta32 gene mutation remained HIV-positive but virus-free(below the limits of detection)after halting antiretroviral therapy.Since this observation in 2009,mutation of the CCR5 gene has become an important target in the prevention and treatment of HIV infection.The CRISPR-Cas9 system,which has been called the biggest biotech discovery in the history of molecular biology,can be used for precise genome engineering with the aim of treating genetic disorders.Currently,the application of gene-editing tools,such as CRISPR-Cas9,for genetic engineering of embryos for use in assisted reproduction is prohibited in much of Europe,the United States,and China.2–3.

Cartilage lacuna-biomimetic hydrogel microspheres endowed with integrated biological signal boost endogenous articular cartilage regeneration

Despite numerous studies on chondrogenesis,the repair of cartilage—particularly the reconstruction of cartilage lacunae through an all-in-one advanced drug delivery system remains limited.In this study,we developed a cartilage lacuna-like hydrogel microsphere system endowed with integrated biological signals,enabling sequential immunomodulation and endogenous articular cartilage regeneration.We first integrated the chondrogenic growth factor transforming growth factor-β3(TGF-β3)into mesoporous silica nanoparticles(MSNs).Then,TGF-β3@MSNs and insulin-like growth factor 1(IGF-1)were encapsulated within microspheres made of polydopamine(pDA).In the final step,growth factor-loaded MSN@pDA and a chitosan(CS)hydrogel containing platelet-derived growth factor-BB(PDGF-BB)were blended to produce growth factors loaded composite microspheres(GFs@μS)using microfluidic technology.The presence of pDA reduced the initial acute inflammatory response,and the early,robust release of PDGF-BB aided in attracting endogenous stem cells.Over the subsequent weeks,the continuous release of IGF-1 and TGF-β3 amplified chondrogenesis and matrix formation.μS were incorporated into an acellular cartilage extracellular matrix(ACECM)and combined with a polydopamine-modified polycaprolactone(PCL)structure to produce a tissue-engineered scaffold that mimicked the structure of the cartilage lacunae evenly distributed in the cartilage matrix,resulting in enhanced cartilage repair and patellar cartilage protection.This research provides a strategic pathway for optimizing growth factor delivery and ensuring prolonged microenvironmental remodeling,leading to efficient articular cartilage regeneration.

Clinical guidelines for indications,techniques,and complications of autogenous bone grafting

Autogenous bone grafts have long been considered the“gold standard”and most effective material in bone regeneration procedures.[1]Autogenous bone grafts are used to repair bone defects caused by nonunion,infection,tumor resection,and spinal and joint fusion.[2]It has been reported that more than 200,000 autologous bone grafts are performed in the United States each year.[3]Although there are no specific statistics on the annual number of bone grafts performed in China,autologous bone grafting is the most common surgical technique in orthopedics.The iliac crest remains the most common donor site,along with the fibula,ribs,tibial metaphysis,proximal humerus,distal radius,and greater trochanter.[4,5]Various bone-graft options provide different amounts and qualities of cortical,cancellous,and corticocancellous bone.[6,7]Autogenous bone graft is osteogenic,histocompatible,provides structural support.

Histone deacetylase inhibition enhances extracellular vesicles from muscle to promote osteogenesis via miR-873-3p

Regular physical activity is widely recognized for reducing the risk of various disorders,with skeletal muscles playing a key role by releasing biomolecules that benefit multiple organs and tissues.However,many individuals,particularly the elderly and those with clinical conditions,are unable to engage in physical exercise,necessitating alternative strategies to stimulate muscle cells to secrete beneficial biomolecules.Histone acetylation and deacetylation significantly influence exercise-induced gene expression,suggesting that targeting histone deacetylases(HDACs)could mimic some exercise responses.In this study,we explored the effects of the HDAC inhibitor Trichostatin A(TSA)on human skeletal muscle myoblasts(HSMMs).Our findings showed that TSA-induced hyperacetylation enhanced myotube fusion and increased the secretion of extracellular vesicles(EVs)enriched with miR-873-3p.These TSA-EVs promoted osteogenic differentiation in human bone marrow mesenchymal stem cells(hBMSCs)by targeting H2 calponin(CNN2).In vivo,systemic administration of TSA-EVs to osteoporosis mice resulted in significant improvements in bone mass.Moreover,TSA-EVs mimicked the osteogenic benefits of exercise-induced EVs,suggesting that HDAC inhibition can replicate exercise-induced bone health benefits.These results demonstrate the potential of TSA-induced muscle-derived EVs as a therapeutic strategy to enhance bone formation and prevent osteoporosis,particularly for individuals unable to exercise.Given the FDA-approved status of various HDAC inhibitors,this approach holds significant promise for rapid clinical translation in osteoporosis treatment.

Advanced surface engineering of titanium materials for biomedical applications:From static modification to dynamic responsive regulation

Titanium(Ti)and its alloys have been widely used as orthopedic implants,because of their favorable mechanical properties,corrosion resistance and biocompatibility.Despite their significant success in various clinical applications,the probability of failure,degradation and revision is undesirably high,especially for the patients with low bone density,insufficient quantity of bone or osteoporosis,which renders the studies on surface modification of Ti still active to further improve clinical results.It is discerned that surface physicochemical properties directly influence and even control the dynamic interaction that subsequently determines the success or rejection of orthopedic implants.Therefore,it is crucial to endow bulk materials with specific surface properties of high bioactivity that can be performed by surface modification to realize the osseointegration.This article first reviews surface characteristics of Ti materials and various conventional surface modification techniques involving mechanical,physical and chemical treatments based on the formation mechanism of the modified coatings.Such conventional methods are able to improve bioactivity of Ti implants,but the surfaces with static state cannot respond to the dynamic biological cascades from the living cells and tissues.Hence,beyond traditional static design,dynamic responsive avenues are then emerging.The dynamic stimuli sources for surface functionalization can originate from environmental triggers or physiological triggers.In short,this review surveys recent developments in the surface engineering of Ti materials,with a specific emphasis on advances in static to dynamic functionality,which provides perspectives for improving bioactivity and biocompatibility of Ti implants.

Identification of prophylaxis and treatment for hospitalized patients associated with venous thromboembolism

To the Editor:Venous thromboembolism(VTE)is a collective term consisting of deep venous thrombosis(DVT)and pulmonary embolism(PE).It is a major worldwide health concern as it affects 5%to 15%of hospitalized patients.Various predisposing factors for VTE occurrence include cancer,surgery,prolonged immobilization,fracture,paralysis,oral contraceptive use,and hereditary coagulopathies.

Osteogenesis effects of magnetic nanoparticles modified-porous scaffolds for the reconstruction of bone defect after bone tumor resection

The treatment of bone defect after bone tumor resection is a great challenge for orthopedic surgeons.It should consider that not only to inhibit tumor growth and recurrence,but also to repair the defect and preserve the limb function.Hence,it is necessary to find an ideal functional biomaterial that can repair bone defects and inactivate tumor.Magnetic nanoparticles(MNPs)have its unique advantages to achieve targeted hyperthermia to avoid damage to surrounding normal tissues and promote osteoblastic activity and bone formation.Based on the previous stage,we successfully prepared hydroxyapatite(HAP)composite poly(lactic-co-glycolic acid)(PLGA)scaffolds and verified its good osteogenic properties,in this study,we produced an HAP composite PLGA scaffolds modified with MNPs.The composite scaffold showed appropriate porosity and mechanical characteristics,while MNPs possessed excellent magnetic and thermal properties.The cytological assay indicated that the MNPs have antitumor ability and the composite scaffold possessed good biocompatibility.In vivo bone defect repair experiment revealed that the composite scaffold had good osteogenic capacity.Hence,we could demonstrate that the composite scaffolds have a good effect in bone repair,which could provide a potential approach for repairing bone defect after bone tumor excision.

A morphological study of age-related changes in medullary characteristics of proximal humerus

To the Editor:Proximal humeral fracture(PHF)predominantly occurs in patients older than 60 years old with severe osteoporosis.[1]Although a majority of PHFs can be treated non-operatively,the complicated ones require surgical fixation.[2]In older individuals,the loss of trabecular structure and the calcar region in the proximal humeral medullary cavity makes them prone to comminuted fracture and loss of medial hinge support,leading to a high rate of implant failure and reoperation.[3]Recent studies have shown that endosteal augments incorporated into the locking plate construct might provide better medullary support and mechanical stability.[1]However,the endosteal augments used in PHF fixation are of different shapes,modes,and positions,which can lead to implant failure and reduction loss.[1,4,5]This may be because of a lack of understanding of the morphological changes that take place in the proximal humerus at different ages.Therefore,in this study,we analyzed and compared the anatomical degeneration pattern of the medullary canal between older and younger patients to have a better understanding of the medullary morphology of proximal humerus anatomically and the application of endosteal support clinically.