Extracellular vesicles loaded dual-network bioactive sealant via immunoregulation and annulus fibrosus repair for intervertebral disc herniation

Intervertebral disc herniation(IVDH)is a common manifestation of intervertebral disc degeneration(IVDD)characterized by inflammation that results in the rupture of the annulus fibrosus(AF)and her-niation of the nucleus pulposus(NP).While current clinical research primarily focuses on regulating the degenerative NP,the crucial role of the AF in maintaining the mechanical stability and metabolic balance of the intervertebral disc(IVD)has been overlooked.Resolving immunoregulation and AF repair is im-perative to effectively prevent recurrent herniation.Therefore,this study introduces a bioactive sealant(OD/GM/QCS-sEVs),which combines gelatin methacryloyl(GM)and oxidized dextran(OD)with quater-nized chitosan(QCS)and incorporates small extracellular vesicles(sEVs).The developed sealant possesses injectability,self-healing capabilities,tissue adhesiveness,and mechanical stability,with an average ad-hesive strength of 109.63 kPa.In vitro experiments demonstrate that OD/GM/QCS-sEVs effectively seal AF defects while preserving mechanical properties comparable to those of a normal IVD.Additionally,the sealant releases sEVs through a pH-responsive mechanism,thereby modulating macrophage polarization to the M2 phenotype via the NF-κB signaling pathway.This mechanism facilitates immunoregulation and anti-inflammatory effects,and promotes stem cell differentiation into fibrocartilage.Animal experiments confirm the ability of OD/GM/QCS-sEVs to seal defects,prevent proteoglycan loss,inhibit IVDD develop-ment,and promote AF regeneration.Overall,OD/GM/QCS-sEVs hold promise as an innovative bioactive sealant for recurrent herniation by resolving immunoregulation and AF regeneration.

CLINICAL OBSERVATION ON LUMBAR INTERVERTEBRAL DISC HERNIATION TREATED BY TRACTION COMBINED WITH ACUPUNCTURE

Objective: To observe the therapeutic effect of traction combined with acupuncture on lumbar intervertebral disc herniation (LIDH). Methods:Eighty-three patients diagnosed as LIDH were randomly divided into treatment group (n=42)and control group (n=41). In the treatment group, besides lumbar traction, electroacupuncture at Jiaji (EX-B 2, L 3～5), Shenshu (BL 23), Qihai (CV 6), Mingmen (GV 4), Huantiao (GB 30), Chengshan (BL 57) and Yanglingquan (GB 34) was added. In the control group, only lumbar traction was applied. Results: In treatment group, the cure plus markedly effective rate was 80.95% with a total effective rate of 92.86%, while in control group, it was 39.02% with a total effective rate of 80.48%. The therapeutic effect in the treatment group was obviously better than that in the control group (P<0.001). Conclusion: Lumbar traction plus EA can effectively alleviate or even eliminate clinical symptoms and signs of lumbar intervertebral disc herniation.

Electroacupuncture at jiājǐ(夹脊 EX-B2) for lumbar intervertebral disc herniation:A randomized controlled trial

Objective： To compare the effect differences of electroacupuncture（EA） at Jiajǐ（夹脊 EX-B2） and conventional acupoints for lumbar intervertebral disc herniation（LIDH） and the factors influenced the effect during the way of data mining.Methods： A total of 160 patients of LIDH were randomly assigned into the EX-B2 group and the conventional acupoints group, 80 cases in each one. The patients in the EX-B2 group received EA at the symmetrical 2 acupoints of the bilateral EX-B2 on the lesion part. The patients in the conventional acupoints group received EA at the tender point of the lesion part, Zhibian（ 秩边BL54）, Huantiao（环跳 GB30）,weǐzhōng（委中BL40）, Chéngshān（承山BL57） and Fúyáng（跗阳BL59） on the affected side. The retain time of the needles is both 45 min. The treatment of the two groups is 3 times a week and for a connective 20 times. The modified Assessment Criteria for Low Lumbar Pain of Japanese Orthopedic Association（JOA）,Visual Analogue Scale（VAS） were evaluated before and after the treatment and at the 6-month follow up.Results：（1） Effective outcomes. JOA score： The JOA score of the patients in the EX-B2 group after treatment was（20.89 士 3.43）, and was（19.35 ±4.02） on the follow-up. Compared with the JOA score（12.35 ±4.42） in the same group before the treatment, there were statistical significant higher（both P0.05）. The JOA score in the EX-B2 group after treatment and on the follow-up were both higher than that of the conventional acupoints group at the same time point（both P0.05）. VAS score： The VAS score of the patients in the EX-B2 group on the 24 h after the first treatment was（4.09 ± 1.81）, and was（2.11 ± 1.30） after the treatment. Compared with the VAS score（4.09 ± 1.81） in the same group before the treatment, there were statistical significant lower（both P0.05）. The VAS score in the EX-B2 group on the 24 h after the first treatment and after treatment showed no statistical differences than that of the conventional acupoints group at the same time point（both P0.05）.（2）Related results from data mining： The middle-aged people and disease duration less than six months, their effect of the immediate treatment was the best. According to JOA score, EA at EX-B2 was better than EA conventional acupoints,either in the process of treatment effect, or in pertinence of the treatment, which were superior to EA conventional acupoints therapy; The best curative effect time of EA at EX-B2 was the first treatment after24 h, and the best curative effect of the conventional acupoints was after the first treatment. The age and disease duration also affected curative effect.Conclusion： The effect of EA at EX-B2 was superior to the conventional acupoints in treating LIDH.

A Study on Extension－Flexion Dynamic Lumbar Spine Radiographsin Patients with Lumbar Intervertebral Disc Herniation

The study has collected a set of clinical materials such as extension-flexion dynamic lum-bar spine radiographs and computerized x-ray tornography of lumbar spine and quantified physical exami-nation from 32 patients with lumbar intervertebral disc herniation, who had gone through a suocessful con-servative treatment. The collection was conducted twice before and after the treatment. With the help oft-test and linear correlation analysis, the study suggests that extensionflexion radiograph of lumbar spineis of important clinical significance in weighing the clinical state of an individual patient, especially forthose who receive conservative treatment. The study emphasizes that the biomechanical disturbance oflumbar spinal column may be from another important pathological element along with the irritation of thenerve root by herniated disc tissue in the pathomechanics of lumbar disc herniation. There is also somediscussion of the computerized X-ray tomography diagnosis in this study. Above all, the author provides anew angle of viewing the trouble by one of the soul principles of traditional Chinese medicine: concept ofholistics .

Electroacupuncture plus waist-strengthening exercises for herniation of lumbar intervertebral disc

Objective To investigate the clinical efficacy of electroacupuncture plus waist-strengthening exercises in treating herniation of lumbar intervertebral disc. Methods Fifty patients with herniation of lumbar intervertebral disc were treated with eleetroaeupuncture at the points of Shiqizhui （十七椎 EX-B 8）, Yaoyangguan（腰阳关 GV 3）, Huantiao （环跳 GB 30）, Yanglingquan （阳陵泉GB 34） and waist-strengthening exercises. The total scores of general symptoms were evaluated before the treatment and after four months and seven months of treatment to compare the therapeutic effects. Results The total scores of general symptoms after four months and seven months of treatment were 15.30±5.66 and 19.08±4.57 respectively, which were much higher than the score of 7.42±2.20 before the treatment （both P〈0.01 ）, in addition, the score after seven months of treatment was higher than that after four months of treatment. The variation of scores in patients with different types after treatment was statistically significant （P〈0.05）, and the best effect can he seen in the blood stagnation type of patients with herniation of hnnbar intervertebral disc, then less the patients with liver and kidney deficiency type. Conclusion Electroacupuneture plus waist-strengthening exercises has a satisfactory therapeutic effect on herniation of lumbar intervertebral diste, the longer course of treatment is, the beffer therapeutic effect achieved.

Reduction in nerve root compression by the nucleus pulposus after Feng's Spinal Manipulation

Ninety-four patients with lumbar intervertebral disc herniation were enrolled in this study. Of these, 48 were treated with Feng＇s Spinal Manipulation, hot fomentation, and bed rest （treatment group）. The remaining 46 patients were treated with hot fomentation and bed rest only （control group）. After 3 weeks of treatment, clinical parameters including the angle of straight-leg raising, visual analogue scale pain score, and Japanese Orthopaedic Association score for low back pain were improved. The treatment group had significantly better improvement in scores than the control group. Magnetic resonance myelography three-dimensional reconstruction imaging of the vertebral canal demonstrated that filling of the compressed nerve root sleeve with cerebrospinal fluid increased significantly in the treatment group. The diameter of the nerve root sleeve was significantly larger in the treatment group than in the control group. However, the sagittal diameter index of the herniated nucleus pulposus and the angle between the nerve root sleeve and the thecal sac did not change significantly in either the treatment or control groups. The effectiveness of Feng＇s Spinal Manipulation for the treatment of symptoms associated with lumbar intervertebral disc herniation may be attributable to the relief of nerve root compression, without affecting the herniated nucleus pulposus or changing the morphology or position of the nerve root.

Comparison between two types of＂Scheuermann disease-like people＂： thoracolumbar disc herniation patients and healthy volunteers with radiological signs of Scheuermann＇s disease

Background Scheuermann＇s disease （SD） is a spinal disorder and includes both a classic form and an atypical form.Interestingly,its existence among the general population as well as the disc disease patients is common.One of our previous studies showed that about 18％ of the hospital staff members meet the SD criteria.On the other hand,another study has demonstrated that 95.2％ of the symptomatic thoracolumbar disc herniation （STLDH） patients meet the SD criteria,which suggests that STLDH is very likely a special form of SD.The purpose of this study was to discriminate the factors contributing to the development of STLDH by comparing STLDH patients with the healthy SD-like hospital staff members.Methods This is a retrospective study including 33 STLDH patients who met the SD criteria and 30 SD-like hospital staff members.The STLDH group was chosen from a group of patients who underwent surgery after a diagnosis of STLDH （T10/11-L1/2） at our hospital between June 2007 and June 2010.SD-like hospital staff members were chosen from a database created in 2007,which contained a lumbar MR and low back pain （LBP） questionnaire of 188 hospital staff members.The demographic and radiologic characteristics were compared between groups.Results There was no statistical difference in sex,age,and height between the two groups.The STLDH patients had higher body weight,boby mass index,and thoracolumbar kyphotic angle than SD-like hospital staff members.In addition,STLDH patients had more levels of Schmorl＇s nodes （3.5±1.7 vs.2.0±1.9,t=3.364,P=0.001） and irregular endplateson （4.0±1.9 vs.2.7±1.9,t=2.667,P=0.010） compared to the SD-like hospital staff members.Conclusions Higher body weight,higher body mass index,larger thoracolumbar kyphosis,and more Schmorl＇s nodes and irregular endplates on MR may be associated with the development of STLDH in ＂SD-like people.＂

Autologous nucleus pulposus transplantation to lumbar 5 dorsal root ganglion after epineurium discission in rats： a modified model of non-compressive lumbar herniated intervertebral disc

Background Nucleus pulposus of intervertebral discs has proinflammatory characteristics that play a key role in neuropathic pain in lumbar herniated intervertebral disc. One of the most commonly used animal models （the traditional model） of non-compressive lumbar herniated intervertebral disc is created by L4-L5 hemilaminectomy and the application of autologous nucleus pulposus to cover the left L4 and L5 nerve roots in rats. However, such procedures have the disadvantages of excessive trauma and low success rate. We proposed a modified model of non-compressive lumbar herniated intervertebral disc in which only the left L5 dorsal root ganglion is exposed and transplanted with autologous nucleus pulposus following incision of epineurium. We aimed to compare the modified model with the traditional one with regard to trauma and success rate. Methods Thirty Sprague-Dawley male rats were randomized into three groups： sham operation group （n=6）, traditional group （n=12）, and modified group （n=12）. The amount of blood loss and operative time for each group were analyzed. The paw withdrawal threshold of the left hind limb to mechanical stimuli and paw withdrawal latency to heat stimuli were examined from the day before surgery to day 35 after surgery. Results Compared with the traditional group, the modified group had shorter operative time, smaller amount of blood loss, and higher success rate （91.7% versus 58.3%, P 〈0.05）. There was no decrease in paw withdrawal latency in any group. The sham operation group had no decrease in postoperative paw withdrawal threshold, whereas the modified and traditional groups had significant reduction in paw withdrawal threshold after surgery （mechanical hyperalgesia）. Conclusions Transplantation of nucleus pulposus onto the L5 dorsal root ganglion following incision of epineurium in rats established an improved animal model of non-compressive lumbar herniated intervertebral disc with less trauma and more stable pain ethology.