Hong-xing Shen

A Novel High Mechanical Property PLGA Composite Matrix Loaded with Nanodiamond-Phospholipid Compound for Bone Tissue Engineering.

A potential bone tissue engineering material was produced from a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), loaded with nanodiamond phospholipid compound (NDPC) via physical mixing. On the basis of hydrophobic effects and physical absorption, we modified the original hydrophilic surface of the nanodiamond (NDs) with phospholipids to be amphipathic, forming a typical core-shell structure. The ND-phospholipid weight ratio was optimized to generate sample NDPC50 (i.e., ND-phospholipid weight ratio of 100:50), and NDPC50 was able to be dispersed in a PLGA matrix at up to 20 wt %. Compared to a pure PLGA matrix, the introduction of 10 wt % of NDPC (i.e., sample NDPC50-PF10) resulted in a significant improvement in the materials mechanical and surface properties, including a decrease in the water contact angle from 80 to 55°, an approximately 100% increase in the Youngs modulus, and an approximate 550% increase in hardness, thus closely resembling that of human cortical bone. As a novel matrix supporting human osteoblast (hFOB1.19) growth, NDPC50-PFs with different amounts of NDPC50 demonstrated no negative effects on cell proliferation and osteogenic differentiation. Furthermore, we focused on the behaviors of NDPC-PFs implanted into mice for 8 weeks and found that NDPC-PFs induced acceptable immune response and can reduce the rapid biodegradation of PLGA matrix. Our results represent the first in vivo research on ND (or NDPC) as nanofillers in a polymer matrix for bone tissue engineering. The high mechanical properties, good in vitro and in vivo biocompatibility, and increased mineralization capability suggest that biodegradable PLGA composite matrices loaded with NDPC may potentially be useful for a variety of biomedical applications, especially bone tissue engineering.

A meta-analysis showing that high signal intensity on T2-weighted MRI is associated with poor prognosis for patients with cervical spondylotic myelopathy

We used PubMed, Medline, and EMBASE to conduct a meta-analysis to determine the significance of high signal intensity on T2-weighted MRI for predicting postoperative prognosis in patients with cervical spondylotic myelopathy (CSM). Although patients with CSM with high signal intensity on T2-weighted MRI usually had a poor prognosis even after undergoing surgery, some researchers have argued recently that high-intensity signals are not associated with postoperative prognosis. Data consistent with the inclusion criteria of this study were cited for meta-analysis using Review Manager 5 Software. The postoperative recovery ratio specified by the Japanese Orthopedic Association (JOA) was assessed using the weighted mean difference (WMD) method. Five articles (one prospective; four retrospective) involving 309 patients with CSM were included. The aggregate WMD with regard to the postoperative JOA recovery ratio between the T2-weighted high signal intensity positive (+) group and the T2-weighted high signal intensity negative (-) group was -6.56, and the 95% confidence interval (CI) was -12.15 to -0.97 (p=0.02). Thus, we concluded that in patients with CSM, the postoperative JOA recovery ratio in the T2-weighted (+) group was lower than that in the T2-weighted (-) group.

Effectiveness of tranexamic acid in reducing blood loss in spinal surgery: a meta-analysis

BackgroundThe aim of present meta-analysis was to evaluate the effectiveness of tranexamic acid (TXA) use in reducing blood loss and the related thrombotic complications in spinal surgery.MethodsThree databases (MEDLINE, EMBASE, and the Cochrane Library) were searched through October 2012 to identify the relevant randomized controlled trials (RCTs) regarding the TXA effective in spinal surgery. Mean differences (MDs) of blood loss, blood transfusions, and postoperative partial thromboplastic time (PTT), odds ratios (ORs) of blood transfusion and thrombotic complication in TXA-treated group compared to placebo group were extracted and combined using random-effect meta-analysis.ResultsA total of 6 RCTs comprising 411 patients were included in the meta-analysis according to the pre-defined selection criteria. TXA-treated group had significantly less amount of blood loss and blood transfusions per patient, and had smaller proportion of patients who required a blood transfusion compared with the placebo group. The use of TXA can significantly reduce the postoperative PTT with weighted MD of -1.59 [(95% confidence interval (CI):-3.07, -0.10] There is a null association between thrombosis complications and the use of TXA.ConclusionWe conclude that the use of TXA in patients undergoing spinal surgery appears to be effective in reducing the amount of blood loss, the volume of blood transfusion, the transfusion rate, and the postoperative PTT. However, data were too limited for any conclusions regarding safety. More high-quality RCTs are required before recommending the administered of TXA in spinal surgery.

Age-related changes of the diffusion tensor imaging parameters of the normal cervical spinal cord

BACKGROUND The diffusion tensor imaging (DTI) parameters of the cervical spinal cord (CSC) changes with age. However, previous studies only examined specific CSC areas. OBJECTIVES To analyze the DTI parameters in all intervertebral space levels of the whole normal CSC and to study the impact of age on these parameters in a Chinese population. METHODS Thirty-six healthy subjects aged 20-77 years were recruited. DTI parameters were calculated for gray matter (GM) and white matter (WM) funiculi in all the CSC intervertebral spaces (C1/2-C6/7). Age-related changes of DTI parameters were analyzed for the GM and WM funiculi. RESULTS Fractional anisotropy (FA) and mean diffusivity (MD) were lower in GM than in WM. MD and FA values were lower in the WM in the lower CSC compared with the upper CSC (all P<0.05), but no difference was observed in GM. In ventral funiculi, MD increased with age, while FA decreased (all P<0.001). In lateral and dorsal funiculi, MD and FA decreased with age (all P<0.001). In GM, MD and FA decreased with age (all P<0.001). Significant age-related changes were observed in FA and MD from GM and WM funiculi. FA was correlated with age in all funiculi (ventral: r=-0.733; lateral: r=-0.468; dorsal: r=-0.607; GM: r=-0.724; all P<0.01). CONCLUSION Important changes in MD and FA were observed with advancing age at all levels of CSC in Chinese patients. DTI parameters may be useful to assess CSC pathology, but the influence of age and segments need to be taken into account in diagnosis.

Enhanced p62 expression triggers concomitant autophagy and apoptosis in a rat chronic spinal cord compression model.

Chronic spinal cord compression is the result of mechanical pressure on the spinal cord, which in contrast to traumatic spinal cord injury, leads to slowly progressing nerve degeneration. These two types of spinal cord injuries may trigger similar mechanisms, including motoric nerve cell apoptosis and autophagy, however, depending on differences in the underlying injury severity, nerve reactions may predominantly involve the conservation of function or the initiation of functions for the removal of irreversibly damaged cells. p62 is a multidomain adapter protein, which is involved in apoptosis and cell survival as well as autophagy, and is a common component of protein aggregations in neurodegenerative diseases. In the present study, a rat chronic spinal cord compression model was used, in which the spinal cord was progressively compressed for six weeks and then constantly compressed for another 10 weeks. As a result Basso, Beattie and Bresnahan locomotor scaling revealed a gradual score decrease until the 6th week followed by constant recovery until the 16th week after spinal cord compression was initiated. During the first eight weeks of the experiment, p62 and nuclear factor-κB (NF-κB) were increasingly expressed up to a constant plateau at 12-16 weeks, whereas caspase 3 exhibited a marginally enhanced expression at 8 weeks, however, reached a constant maximum peak 12-16 weeks after the beginning of spinal cord compression. It was hypothesized that, in the initial phase of spinal cord compression, enhanced p62 expression triggered NF-κB activity, directing the cell responses mainly to cell survival and autophagy, whereas following eight weeks of spinal cord compression, caspase 3 was additionally activated indicating cumulative elimination of irreversibly damaged nerve cells with highly activated autophagy.

Value of magnetic resonance diffusion tensor imaging ratios in evaluating clinical symptoms and prognosis of cervical spondylotic myelopathy

Objective To explore the value of the apparent diffusion coefficient(ADC)ratio and fractional anisotropy(FA)ratio of magnetic resonance(MR)diffusion tensor imaging(DTI)in evaluating the clinical symptoms,prognosis of cervical spondylotic myelopathy(CSM).Methods Thirty-six healthy subjects and fifty CSM patients were involved and received MRI examination.Regions of interest(ROIs)were selected in the ventral funiculus(VF),lateral funiculi(LF),dorsal funiculus(DF),and central gray matter(GM)for ADC and FA measurements.In the control group,ADC and FA ratios were calculated using the original values at the C3/4,C4/5,C5/6,and C6/7levels to divide the corresponding values at their C1/2levels.In the CSM group,ADC and FA ratios were calculated using the ADC and FA values at the most compressed levels to divide the corresponding values at their C1/2levels.In the control group,the variances of the two ratios were compared between different cervical levels and ages.CSM patients were divided into mild,moderate,and severe group according to the preoperative Japanese Orthopaedic Association(JOA)scoring system,and were divided into well,moderate,and poor group according to the postoperative JOA recovery rates.Correlations between DTI parameters,DTI ratios of the VF,LF,DF,and GM of the CSM patients and the JOA scores,JOA recovery rates were assessed among different clinical symptom subgroups and prognosis subgroups.Results In control group,DTI ratios(ADC ratios and FA ratios)in VF,LF,DF,and GM were significantly different between C3/4,C4/5,C5/6,and C6/7levels(P0.05),but not found between different age subgroups.Correlations between DTI ratios of the VF,LF,DF,and GM and JOA scores,JOA recovery rates were significantly superior than the correlations between DTI parameters and JOA scores,JOA recovery rates(P0.05 or P0.01),with the FA ratio being superior to the ADC ratio.Compared with normal control group,the ADC ratios increased gradually in order and FA ratios decreased gradually in the mild,moderate,and severe injury subgroups(P0.05).Compared with normal control group,the ADC ratios increased gradually in order and FA ratios decreased gradually in the well,moderate,and poor recovery subgroups(P0.05).Conclusion DTI ratios might eliminate the influence of age in evaluating the clinical symptoms and prognosis of CSM.Therefore DTI ratios,compared with DTI parameters,may better evaluate the clinical symptoms,prognosis of CSM.

Role of metalloproteinases and their inhibitors in intervertebral disc degeneration:research progress

Intervertebral disc degeneration(IVDD)is characterized by the excessive degradation of extracellular matrix(ECM),which underlies many spine-related disorders.Matrix metalloproteinases(MMPs)and a disintegrin metalloproteinases with thrombospondin motifs(ADAMTSs)are believed to be the major proteolytic enzymes responsible for ECM degradation.This review summarizes the current literatures on gene expression and regulation of MMPs,ADAMTSs,and tissue inhibitors of metalloproteinases(TIMPs)in IVDD.Reports have showen that specific MMPs(MMP-1,-2,-3,-7,-8,-10,and-13)and ADAMTS(ADAMTS-1,-4,and-15)are upregulated in human degenerated intervertebral discs.Tissue inhibitor of metalloproteinase-3is downregulated and TIMP-1 is upregulated in human degenerated intervertebral discs relative to nondegenerated intervertebral discs.Regulation of the MMP and ADAMTS expression is affected by many factors including mechanical,inflammatory,oxidative stress,and so on.Genetic predisposition also plays an important role in expression of MMP-1,-2,-3,and-9.Upregulation of MMP and ADAMTS expression is implicated in ECM destruction,which can lead to the development of IVDD.Future IVDD therapeutics may target specific MMPs and ADAMTSs which is essential in the pathological proteolysis of ECM.

Preparation of individualized navigation templates for pedicle screw insertion in goats using a three-dimensional printing forming technique

Objective To investigate the feasibility of preparing individualized navigation templates for pedicle screw insertion using a three-dimensional printing forming technique,and to evaluate the accuracy of template-assisted pedicle screw insertion.Methods Five male Chongming goats were selected and total spine CT-scan was performed.After the original Dicom data were imported into the Mimics software,the C3-6,T3-6and L3-6spinal column models were created to design and generate the cavity models based on a three-dimensional printing forming technique.The navigation template was created with a wellestablished pedicle screw path using a free-hand procedure,and then bilateral pedicle screw insertion was done assisted by the navigation templates.CT-scan was taken again postoperatively to access the position of the screws.Results Totally 60 navigation templates were prepared and 119 pedicle screws were implanted under the assistance of these templates,with one pedicle screw insertion failed due to a congenital deformity.CT-scan axial images indicated that 114 pedicle screws were completely contained within the pedicles,while 5screws perforating the pedicle walls.Sagittal images showed accurate screw placement except for 2screws perforating into the foramen.Conclusion The present study indicates that Mimics software is a feasible and precise method for establishing spinal column and related cavity model based on CT-scan images.Pedicle screw insertion assisted by a three-dimensional printing model is highly accurate and easy to perform,which may be a new alternative to conventional technique.

Application of diffusion tensor imaging in cervical spondylotic myelopathy：recent advance

Cervical spondylotic myelopathy(CSM),commonly seen in the elderly,is caused by the chronic compression of the spinal cord induced by cervical disc degradation.Magnetic resonance imaging(MRI)can clearly reveal spinal canal stenosis,morphology and signal changes of compressed spinal cord,but it falls short in demonstrating the slight changes and microstructure of the spinal cord and is not capable of quantitative analysis.Diffusion tensor imaging(DTI)is a new MRI technique which can display the water molecule diffusion characteristics in the nerve fiber cells,with the evaluation parameters mainly including the apparent diffusion coefficient(ADC)and the fractional anisotropy(FA).Moreover,it can clearly display the fiber bundle of the spinal cord with the diffusion tensor tractography(DTT),making it currently the only non-invasive way to trace the white matter fiber bundle.Studies have reported that DTI parameters compared with routine MRI is more sensitive in early diagnosis,neuronal function evaluation,and prognosis prediction of CSM.DTT can clearly display the morphology and dynamic changes of spinal nerve bundles,evaluate the neuronal function and predict the post-operation prognosis.There are still limitations for spinal DTI,such as lack of standard method for measuring and analyzing DTI parameters,and whether DTT can reflect the true pathological status of spinal cord.Here we reviewed the development of DTI technology and its role in CSM.