Activated allograft combined with induced menbrane technique for the reconstruction of infected segmental bone defects.

This study was desinged to evaluate the efficacy and safety of activated allograft combined with the induced membrane technique for reconstruction of infected segment bone defects of lower limbs. A retrospective analysis was conducted on 19 patients from May 2015 to February 2017. After debridements, the bone defects were filled with antibiotic bone cement to form the induced membrane. Autologous mesenchymal stem cells were seeded onto allografts to construct activated allograft, which was implanted into the induced membrane after infection was controlled. The clinical efficacy and complications were observed. 19 patients with 20 infected segment bone defect were evaluated. The average deficit size was 11.08 (4-17) cm in length. After a mean follow-up of 71.84 (61-82) months, bone union was achieved in 16 patients (17 sites), resulting in a final union rate of 84.21% (16/19 patients). The average bone union time was 10.18 (5-28) months. There were 2 patients with recurrence of infection, 3 patients with graft absorption, and 1 patient with malunion due to implant breakage. There were no graft-related complications. This study provides clinical significance for the treatment of patients with insufficient autologous bone.

[Commentary on relevant issues in surgical treatment of spinal metastatic tumors].

The multidisciplinary treatment model led by surgery has become a comprehensive strategy and overall concept for the treatment of spinal metastatic tumors. But the surgical treatment of spinal metastatic tumors is different from primary malignant tumors of the spine. Surgery is only a part of the multidisciplinary comprehensive treatment. Therefore, the following aspects need to be evaluated comprehensively based on the survival assessment, evaluation of spinal stability damage, nerve dysfunction, and oncological characteristics of the metastatic tumors with a reasonable surgical intervention. The attention should be paid to the minimally invasive treatment of spinal metastases, progress of new radiotherapy technology, neoadjuvant chemotherapy, targeted drug therapy and other medical treatment to make a comprehensive and individualization decision which is benefit to relieve patients ' pain, reconstruct spinal stability and avoid paralysis. While improving patient survival, increasing local tumor control rate and possibly prolonging survival time, avoiding excessive surgery as much as possible.

Glucocorticoid-loaded pH/ROS dual-responsive nanoparticles alleviate joint destruction by downregulating the NF-κB signaling pathway.

Rheumatoid arthritis (RA) is an autoimmune disease causing severe symptoms that are difficult to treat. Nano-drug delivery system is recognized as a promising strategy for management of RA. However, how to thoroughly release payloads from nanoformulations and synergistic therapy of RA needs to be further investigated. To address this issue, a pH and reactive oxygen species (ROS) dual-responsive, methylprednisolone (MPS)-loaded and arginine-glycine-aspartic acid (RGD)-modified nanoparticles (NPs) was fabricated using phytochemical and ROS-responsive moiety co-modified α-cyclodextrin (α-CD) as a carrier. In vitro and in vivo experiments verified that the pH/ROS dual-responsive nanomedicine could be efficiently internalized by activated macrophages and synovial cells, and the released MPS could promote transformation of M1-type macrophages into M2 phenotype, thereby down-regulating pro-inflammatory cytokines. In vivo experiments demonstrated that the pH/ROS dual-responsive nanomedicine was remarkably accumulated in the inflamed joints of mice with collagen-induced arthritis (CIA). The accumulated nanomedicine could obviously relieve joint swelling and cartilage destruction without obvious adverse effects. Importantly, the expression of interleukin-6 and tumor necrosis factor-α in the joints of CIA mice were significantly inhibited by the pH/ROS dual-responsive nanomedicine in comparison with free drug and non-targeted counterparts. In addition, the expression of the NF-κB signaling pathway molecule P65 was also significantly decreased by nanomedicine-treatment. Our results reveal that MPS-loaded pH/ROS dual-responsive NPs can effectively alleviate joint destruction via down-regulation of the NF-κB signaling pathway. STATEMENT OF SIGNIFICANCE: Nanomedicine is recognized as an attractive method for the targeting treatment of rheumatoid arthritis (RA). To thorough release of payloads from nanoformulations and synergistic therapy of RA, herein, a phytochemical and ROS-responsive moiety co-modified α-cyclodextrin was used as a pH/ROS dual-responsive carrier to encapsulate methylprednisolone to manage RA. The fabricated nanomedicine can effectively release its payloads under pH and/or ROS microenvironment, and the released drugs dramatically promote transformation of M1-type macrophages into M2 phenotype to reduce the release of pro-inflammatory cytokines. The prepared nanomedicine also obviously decreased the NF-κB signaling pathway molecule P65 expression in the joints, thereby down-regulating pro-inflammatory cytokines expression to alleviate joint swelling and cartilage destruction. We provided a candidate for the targeting treatment of RA.

Endothelial Cells Promote Migration of Mesenchymal Stem Cells via PDGF-BB/PDGFRß-Src-Akt in the Context of Inflammatory Microenvironment upon Bone Defect.

Homing of mesenchymal stem cells (MSCs) to the defect site is indispensable for bone repair. Local endothelial cells (ECs) can recruit MSCs; however, the mechanism remains unclear, especially in the context of the inflammatory microenvironment. This study was aimed to investigate the role of ECs in MSCs migration during the inflammatory phase of bone repair. The inflammatory microenvironment was mimicked in vitro via adding a cytokine set (IL-1ß, IL-6, and TNF-α) to the culture medium of ECs. The production of PDGF-BB from ECs was measured by ELISA. Transwell and wound healing assays were employed to assess MSCs migration toward ECs and evaluate the implication of PDGF-BB/PDGFRß. A series of shRNA and pathway inhibitors were used to screen signal molecules downstream of PDGF-BB/PDGFRß. Then, mouse models of femoral defects were fabricated and DBM scaffolds were implanted. GFP+ MSCs were injected via tail vein, and the relevance of PDGF-BB/PDGFRß, as well as screened signal molecules, in cell homing was further verified during the early phase of bone repair. In the mimicked inflammatory microenvironment, MSCs migration toward ECs was significantly promoted, which could be abrogated by pdgfrb knockout in MSCs. Inhibition of Src or Akt led to negative effects analogous to pdgfrb knockout. Blockade of JNK, MEK, and p38 MAPK had no impact. Meanwhile, the secretion of PDGF-BB from ECs was evidently motivated by the inflammatory microenvironment. Adding recombinant PDGF-BB protein to the culture medium of ECs phenocopied the inflammatory microenvironment with regard to attracting MSCs, which was abolished by pdgfb, src, or akt in MSCs. Moreover, pdgfb knockout suppressed the expression and phosphorylation of Src and Akt in migrating MSCs. Src knockout impaired Akt expression but not vice versa. In vivo, reduced infiltration of CD31+ ECs was correlated with diminished PDGF-BB in local defect sites, and silencing pdgfb, src, or akt in MSCs markedly hampered cell homing. Together, these findings suggest that in the inflammatory microenvironment, MSCs migrate toward ECs via PDGF-BB/PDGFRß and the downstream Src-Akt signal pathway.

The clinical use of the enriched bone marrow obtained by selective cell retention technology in treating adolescent idiopathic scoliosis.

PURPOSE: This retrospective study aimed to evaluate the curative effect of allografts in combination with bone marrow enrichment realised by selective cell retention (SCR) technology in treating adolescent idiopathic scoliosis (AIS). METHODS: From July 2014 to September 2016, 18 consecutive patients with AIS were treated by posterior fusion and pedicle screw instrumentation. Bone marrow aspirates were obtained and enriched by SCR technology to fabricate bone grafts in combination with allogeneic bones, which were implanted for spinal fusion. Postoperatively, the patients were observed for a minimum of 18 months, with a mean follow-up period of 48 months. The results were assessed both clinically and radiographically. All adverse events and complications were recorded. RESULTS: A total of 9 male and 9 female patients were included, with an average age of 15.6 years (range, 12-20). The average preoperative Cobb angle was 56° (range, 47°-85°). The average number of levels fused was 11 (range, 9-13). SCR could be accomplished intraoperatively, only consuming approximately 20 â€‹min. The enriching multiples of measured cellular elements were approximately 2.3-4.2. At final follow-up, the average Cobb angle correction was 83% (range, 61-96%). There was no obvious loss in correction with an average loss of 1.1° (2%). The visual analogue scale score and the Oswestry Disability Index score at final follow-up were significantly ameliorated than those preoperatively. The Scoliosis Research Society 30 questionnaire revealed remarkable improvement in the domains "pain", "self-image/appearance", and "satisfaction with management". There was neither pseudarthrosis nor severe complication. CONCLUSION: The use of SCR technology could be considered as an effective method for promoting spinal fusion in treating AIS. We proposed a safe, simple, and rapid approach to obtain effective bone grafts for spinal fusion. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Enriched bone marrow obtained by selective cell retention technology has the potential to promote spinal fusion for the treatment of adolescent idiopathic scoliosis.

Efficacy of Biocage in treating single-segment lumbar degenerative disease in patients with high risk of non-fusion: a prospective controlled study with at least 2 years' follow-up.

OBJECTIVE: To evaluate the clinical efficacy of an allogeneic bone cage (Biocage; Beijing Datsing Bio-Tech Co., Ltd., Beijing, China) for treatment of single-segment lumbar degenerative disease in patients with a high risk of non-fusion. METHODS: From January 2013 to December 2016, 67 patients who underwent lumbar fusion were divided into the Biocage group (n = 33) and polyether ether ketone (PEEK) group (n = 34). The patients were followed up for 24 to 48 months. The mean intervertebral height of the fusion level, fusion rate, height of the intervertebral foramen, visual analog scale score, and Oswestry disability index were compared. RESULTS: The PEEK group had a lower fusion rate than the Biocage group (88.24% vs. 90.91%), although the difference was not statistically significant. During follow-up, the height of the intervertebral space was similar between the Biocage and PEEK groups (12.88 ± 0.45 and 12.84 ± 1.01 mm, respectively). The height of the intervertebral foramen was larger in the Biocage than PEEK group (20.67 ± 1.34 vs. 20.00 ± 2.05 mm). Good clinical efficacy was achieved in both groups. CONCLUSION: The Biocage is efficient and safe for treatment of single-segment lumbar degenerative disease in patients with a high risk of non-fusion.

Tricortical iliac crest allograft with anterolateral single rod screw instrumentation in the treatment of thoracic and lumbar spinal tuberculosis.

To assess the effectiveness of tricortical iliac crest allografts with anterolateral instrumentation after single-stage surgery for thoracic and lumbar spinal tuberculosis (TB). Fifty-six patients with thoracic and lumbar spinal TB underwent single-stage anterior radical debridement, interbody fusion with tricortical iliac crest allografts and anterolateral single rod instrumentation. All patients were given 18 months of antituberculosis chemotherapy. The patients were followed up regularly, and their clinical manifestations, roentgenogram results, erythrocyte sedimentation rate (ESR) and liver function test were the results to be concerned. Radiographs were analysed before surgery, immediately after surgery, and at the final follow-up examination. Mean follow-up period was 37.5 months in 52 patients, and 4 patients were lost to follow-up. No patients had superficial wound infections, and all the incisions healed within 2 weeks. No graft fracture, collapse, or sliding was observed. The average bony fusion time was 10.6 months. Bony fusion was observed in all 52 patients within 18 months. The average degrees of kyphotic correction loss for thoracic and lumbar spine were 6.71° and 2.78° respectively. Although it took a long time to achieve solid fusion, tricortical iliac crest allografts were found to be convenient and safe to be used in spinal TB surgery. They may be effective options for interbody fusion, deformity correction and correction maintenance with anterolateral single rod instrumentation.

Comparison of Individual Tissue-Engineered Bones and Allogeneic Bone in Treating Bone Defects: A Long-Term Follow-Up Study.

The treatment of bone defects has always been a challenge for orthopedic surgeons. The development of tissue engineering technology provides a novel method for repairing bone defects and has been used in animal experiments and clinical trials. However, there are few clinical studies on comparing the long-term outcomes of tissue-engineered bones (TEBs) and other bone grafts in treating bone defects, and the long-term efficiency of TEBs remains controversial. Therefore, a study designed by us was aimed to compare the long-term efficacy and safety of individual tissue-engineered bones (iTEBs) and allogeneic bone granules (ABGs) in treating bone defects caused by curettage of benign bone tumors and tumor-like lesions. From September 2003 to November 2009, 48 patients who received tumor curettage and bone grafting were analyzed with a mean follow-up of 122 mo (range 60 to 173 mo). Based on implant style, patients were divided into groups of iTEBs (n = 23) and ABGs (n = 25). Postoperatively, the healing time, healing quality, incidence of complications, and functional scores were compared between the two groups. The Musculoskeletal Tumor Society functional evaluation system and Activities of Daily Living Scale scores were significantly improved in both groups with no significant difference. The average healing time of ABGs was longer than that of iTEBs (P < 0.05). At the final follow-up, iTEBs had a better performance in the bone healing quality evaluated by modified Neer classification (P < 0.05). In the group of iTEBs, the complication and reoperation rate was lower than that in the group of ABGs, with no tumorigenesis or immune rejection observed. In summary, for treating bone defects caused by tumor curettage, iTEBs were safe, effective, and tagged with more rapid healing speed, better healing outcome, and lower complication and reoperation rate, in comparison with ABGs.

Transforaminal debridement with a posterior-only approach involving placement of an interbody bone graft combined with diseased vertebral fixation for the treatment of thoracic and lumbar tuberculosis: Minimum 5-year follow-up.

The aim of this study was to evaluate the clinical and imaging results of transforaminal debridement with a posterior-only approach involving placement of an interbody bone graft combined with diseased vertebral fixation for the treatment of thoracic and lumbar tuberculosis (TB) with a minimum 5-year follow-up.Sixty-five patients who presented with active thoracic and lumbar TB between October 2006 and August 2013 were retrospectively analyzed: 20 were thoracic TB (group A), 17 were thoracolumbar TB (group B), and 28 were lumbar TB (group C). The patient data, operating time, blood loss, Visual Analog Scale score, Oswestry Disability Index score, correction of kyphosis, recovery of neurological function, and complications were recorded and analyzed.The patients were followed for 68.7 ±â€Š17.8 months. The preoperative average Cobb angles of kyphosis in patients in groups A, B, and C significantly decreased from 28.2 ±â€Š11.9°, 30.5 ±â€Š16.9°, and 10.9 ±â€Š8.8° before surgery to 8.0 ±â€Š5.4°, 5.0 ±â€Š4.1°, and -4.4 ±â€Š1.6° (- indicates lordosis) after surgery, respectively. At the final follow-up time, the Cobb angles were 9.2 ±â€Š6.1°, 6.8 ±â€Š10.0°, and -3.7 ±â€Š2.0°, respectively. The postoperative Cobb angles of kyphosis were significantly improved in all groups (P < .05). The correction loss angles were larger in groups A and B than in group C (P > .05). The operating time, blood loss, and complications were not significantly different between the groups (P > .05). Three (4.6%) patients developed unhealed TB during postoperative anti-TB treatment, and 6 patients (9.2%) with TB relapsed after healing from surgery.The posterior-only approach for the surgical treatment of thoracic and lumbar TB achieved satisfactory outcomes over long-term follow-up. The implantation of pedicle screws in diseased vertebrae reduced the range of fixation, but patients with thoracic and thoracolumbar TB should undergo fixation to at least 1 adjacent normal segment. There were some cases of recurrence after TB healed, and long-term follow-up is therefore necessary.

Modification of PLGA Scaffold by MSC-Derived Extracellular Matrix Combats Macrophage Inflammation to Initiate Bone Regeneration via TGF-ß-Induced Protein.

The immunologic response toward chronic inflammation or bone regeneration via the accumulation of M1 or M2 macrophages after injury could determine the fate of biomaterial. Human umbilical cord mesenchymal stem cells (hUCMSCs) have a pivotal immunomodulatory property on directing macrophage behaviors. Herein, for the first time, 3D-printed poly(lactide-co-glycolide) (PLGA) scaffolds modified with hUCMSC-derived extracellular matrix (PLGA-ECM) are prepared by a facile tissue engineering technique with physical decellularization and 2.44 ± 0.29 mg cm-3 proteins immobilized on the PLGA-ECM contain multiple soluble cytokines with a sustainable release profile. The PLGA-ECM not only attenuates the foreign body response, but also improves bone regeneration by increasing the accumulation of M2 macrophages in an improved heterotopic transplantation model of SCID mice. Furthermore, the PLGA-ECM scaffolds with the knockdown of transforming growth factor-ß-induced protein (TGFßI/ßig-H3) demonstrate that M2 macrophage accumulation improved by the PLGA-ECM could be attributed to increasing the migration of M2 macrophages and the repolarization of M1 macrophages to M2 phenotype, which are mediated by multiple integrin signaling pathways involving in integrin ß7, integrin α9, and integrin ß1 in a TGFßI-dependent manner. This study presents an effective surface modification strategy of polymeric scaffolds to initiate tissue regeneration and combat inflammatory response by increasing M2 macrophage accumulation.

Individual Tissue-Engineered Bone in Repairing Bone Defects: A 10-Year Follow-Up Study.

Bone defects caused by various causes remain a major problem in orthopedic clinics. A number of different treatments have been developed and proposed, but until now, none has proven to be completely satisfactory. For 26 patients with bone defects but limited autologous bone source or allogeneic bone graft failure, we used individual tissue-engineered bones (iTEBs) for repairing, which were constructed by autologous bone marrow mesenchymal stem cells and allogenic decalcified bone matrix (DBM) scaffolds. The clinical outcomes, including efficacy and safety, were evaluated by radiological examinations, postoperative function recovery score and laboratory tests. Twenty-six patients, including 18 men and 8 women, were followed up for an average of 10 years to analyze the long-term outcome. The mean healing time for patients with lacunar bone defects was 3.87 ± 2.01 months (range, 2-9 months) and that for structural bone defects was longer than 12 months. The Musculoskeletal Tumor Society functional evaluation system and the Barthel Index scores were significantly improved during the long-term follow-up. The white blood cell, erythrocyte sedimentation rate, C reactive protein, complement, immunoglobulins, and liver and renal functions were not significantly affected by bone grafting. One patient with bone cyst relapsed at 3 years postoperatively and achieved bone healing after re-transplantation. No tumorigenesis, tumor metastasis, or blood transmissible disease was found in the whole process. The results demonstrated that iTEBs were effective and safe for repairing bone defects in the long period, especially for those with lacunar bone defects and limited autograft source. Impact statement Currently, controversies exist about the long-term safety and effectiveness of the clinical application of tissue-engineered bones (TEBs) due to potential tumorigenesis, immune rejection, disease transmission, and others. In this study, we show that individual TEBs constructed by autologous MSCs and allogenic decalcified bone matrix are reliable for repairing bone defects in regard to its long-term safety and effectiveness. Our study provides experience and basis about the clinical application of TEBs in the treatment of bone defects.

Clinical Efficacy of Three Surgical Approaches for the Treatment of Cervicothoracic Tuberculosis: A Multicenter Retrospective Study.

OBJECTIVE: To evaluate the efficacy of three surgical approaches for the treatment of cervicothoracic tuberculosis. METHODS: This is a multicenter retrospective study. We analyzed 74 patients with cervicothoracic tuberculosis who were treated in six institutions between January 2000 and January 2015. There were 37 male and 37 female patients, with an average age of 24 years (range, 5-62 years). The operative method was selected according to the indications. A total of 33 patients underwent one-stage anterior surgery (group A); 16 underwent a combined anterior and posterior surgery (group B) and 25 underwent one-stage posterior surgery (group C). Clinical outcomes, laboratory indexes, and radiological results were analyzed. RESULTS: All cases were followed up for approximately 36-96 months post-surgery (average, 39 months). At the last follow-up, patients in all three groups had achieved bone fusion, with pain relief and neurological recovery. No major vessel and nerve injuries were found during the operation. There were significant differences before and after treatment for visual analogue scale (VAS), neck disability index (NDI), and Japanese Orthopedic Association (JOA) score (P < 0.001). Three surgical strategies significantly improved kyphosis (P < 0.001). CONCLUSION: The choice of operation for cervicothoracic tuberculosis should be selected based on the pathological changes, scope, and general physical condition of the patient. The indication for a posterior approach is narrow and it should be used selectively. The combined anterior and posterior approach involved a longer operating time, larger blood loss, and greater trauma, and also required a higher level of surgical skill. Therefore, the indications for this approach should be strictly controlled. Anterior approach surgery for the treatment of cervicothoracic tuberculosis showed excellent efficacy and fewer complications.

Comparison of Anterior only and Combined Anterior and Posterior Approach in Treating Lumbosacral Tuberculosis.

A combined anterior and posterior (AP) surgical approach is a popular treatment modality of lumbosacral tuberculosis, but it is often traumatic and complicated. The present study aims to find whether the anterior only approach with the ARCH plate system is less invasive than the AP approach in treating lumbosacral tuberculosis. The ARCH plate system is an innovative anatomic lumbosacral anterior multi-directional locking plate system which was devised with due consideration to the anatomic features of the lumbosacral spine and irregular destruction of involved vertebral endplates. In this retrospective study, 32 patients with lumbosacral tuberculosis underwent surgeries via either the anterior only approach (ARCH group, 18 patients) using the ARCH system or the conventional combined anterior and posterior approach (AP group, 14 patients). American Spinal Injury Association (ASIA) scores, Visual Analogue Scale (VAS) scores, Oswestry Disability Index (ODI), bone union status, ESR, CRP, intervertebral foraminal height between L5 and S1, the vertical height between the anterior upper edge of L5 and S1 vertebral body, lumbosacral angle, and the physiological lordosis of between L1 and S1 from both groups were recorded and compared. All patients were followed up for at least two years. The average duration of operation, blood loss, and length of hospital admission of the ARCH group (154.6 min, 361.1 ml&18.3days) was significantly smaller and shorter(p < 0.001, p < 0.001 & p = 0.008) that those of the AP group(465.5 min, 814.3 ml & 24.6days). The ODI score(p = 0.08, 0.471, 0.06, 0.07, 0.107), the VAS score(p = 0.099, 0.249, 0.073, 0.103, 0.273), the intervertebral foraminal height between L5 and S1(p = 0.826, 0.073, 0.085), L5-S1 height(p = 0.057, 0.234, 0.094), lumbosacral angle(p = 0.052, 0.242, 0.825), and L5-S1 lordosis(p = 0.146, 0.129, 0.053) of both groups showed no significant difference in any of the time points. The anterior only approach using the ARCH system is as effective as the combined anterior and posterior approach and is less traumatic in treating lumbosacral tuberculosis.

Clinical and radiological results comparison of allograft and polyetheretherketone cage for one to two-level anterior cervical discectomy and fusion: A CONSORT-compliant article.

BACKGROUND: Recently, many kinds of cages for cervical fusion have been developed to avoid the related complications caused by tricortical iliac crest graft. The existing literature has reported the excellent clinical efficacy and superior fusion rate. However, various types of cages have their own disadvantages. Which bone graft material is the best choice for cage with the fewest complications? At present, there is still no conclusion. METHODS: By reviewing patients with 1 to 2-level cervical degenerative disease in our hospital with a novel cage made of allograft or polyetheretherketone (PEEK), we evaluated the efficacy and reliability of the new cage in anterior cervical discectomy and fusion (ACDF). From 2015 to 2016, a prospective review of 58 and 49 consecutive cases with spondylotic radiculopathy or myelopathy undergoing ACDF using allograft (group A) and PEEK (group B) cage were performed. The follow-up ranged from 12 to 40 months. Intraoperative index, clinical outcome and complications were recorded. Radiographs evaluated segmental and overall cervical lordosis, the height of the intervertebral space, interbody height ratio (IHR), cage positioning, and fusion state. RESULTS: A total of 134 cages were implanted. Compared to preoperatively, the visual analog scale (VAS) and neck disability index (NDI) were reduced postoperatively without any change during the subsequent follow-up in both groups. There was no migration or extrusion of the cages at the latest follow-up. There were 2 and 4 patients suffering dysphagia respectively. In both groups, the intervertebral height, IHR, segmental and overall cervical lordosis were significantly greater than pre-operation (P < .05) and were maintained at the last follow-up, but were not statistically significant (P > .05). The allograft group achieved a fusion rate of 100% (58/58) according to CT scans at 3 months post-operation, while PEEK group was 91.8% (45/49), which reached 95.9% (47/49) at 6 months and 100% at 12 months. In addition, the fusion state was maintained in all patients at the last follow-up. CONCLUSION: Our data showed that the new allograft cage is superior to the PEEK cage in providing a high fusion rate and fewer complications after 1-level and 2-level ACDF procedures. It may represent an excellent alternative to other cages.

Bone Marrow-Derived CD44+ Cells Migrate to Tissue-Engineered Constructs via SDF-1/CXCR4-JNK Pathway and Aid Bone Repair.

BACKGROUND AND AIMS: Host-derived cells play crucial roles in the regeneration process of tissue-engineered constructs (TECs) during the treatment of large segmental bone defects (LSBDs). However, their identity, source, and cell recruitment mechanisms remain elusive. METHODS: A complex model was created using mice by combining methods of GFP+ bone marrow transplantation (GFP-BMT), parabiosis (GFP+-BMT and wild-type mice), and femoral LSBD, followed by implantation of TECs or DBM scaffolds. Postoperatively, the migration of host BM cells was detected by animal imaging and immunofluorescent staining. Bone repair was evaluated by micro-CT. Signaling pathway repressors including AMD3100 and SP600125 associated with the migration of BM CD44+ cells were further investigated. In vitro, transwell migration and western-blotting assays were performed to verify the related signaling pathway. In vivo, the importance of the SDF-1/CXCR4-JNK pathway was validated by ELISA, fluorescence-activated cell sorting (FACS), immunofluorescent staining, and RT-PCR. RESULTS: First, we found that host cells recruited to facilitate TEC-mediated bone repair were derived from bone marrow and most of them express CD44, indicating the significance of CD44 in the migration of bone marrow cells towards donor MSCs. Then, the predominant roles of SDF-1/CXCR4 and downstream JNK in the migration of BM CD44+ cells towards TECs were demonstrated. CONCLUSION: Together, we demonstrated that during bone repair promoted by TECs, BM-derived CD44+ cells were essential and their migration towards TECs could be regulated by the SDF-1/CXCR4-JNK signaling pathway.

Surgical treatment of thoracolumbar spinal tuberculosis-a multicentre, retrospective, case-control study.

BACKGROUND: The purpose of this multicentre, retrospective study was to evaluate the safety and efficacy of different surgical approaches for treating thoracolumbar tuberculosis. METHODS: This study reviewed 132 patients with thoracolumbar tuberculosis in six institutions between January 1999 and January 2015 surgically treated by an anterior-only approach (n = 22, group A), an anterior combined with posterior approach (n = 79, group B), and a posterior-only approach (n = 31, group C). All patients were treated with standard antituberculosis drugs pre- and postoperatively and were followed regularly after surgery. Clinical symptoms, nerve function, and the erythrocyte sedimentation rate were observed, and kyphosis correction and bone fusion were evaluated by X-ray or computed tomography. RESULTS: At the last follow-up, all patients had achieved bone fusion, relief from pain, and neurological recovery. The Cobb angle was improved; however, the Cobb angle showed a degree of loss at the final follow-up after all three surgical approaches. Further comparisons revealed a difference in angle loss at the final follow-up among the three groups; groups B and C were superior to group A in maintenance of the correction. The posterior-only approach was characterized by a shorter operative time and reduced blood loss. CONCLUSIONS: Surgery by a posterior-only approach is superior to that by an anterior-only approach and anterior combined with posterior approach in terms of permanent kyphosis correction and spinal stability maintenance. Therefore, we recommend surgery by a posterior-only approach as the optimized treatment for thoracolumbar tuberculosis if the indications for this treatment are met.

EPC-derived exosomes promote osteoclastogenesis through LncRNA-MALAT1.

Bone repair involves bone resorption through osteoclastogenesis and the stimulation of neovascularization and osteogenesis by endothelial progenitor cells (EPCs). However, the role of EPCs in osteoclastogenesis is unclear. In this study, we assess the effects of EPC-derived exosomes on the migration and osteoclastic differentiation of primary mouse bone marrow-derived macrophages (BMMs) in vitro using immunofluorescence, western blotting, RT-PCR and Transwell assays. We also evaluated the effects of EPC-derived exosomes on the homing and osteoclastic differentiation of transplanted BMMs in a mouse bone fracture model in vivo. We found that EPCs cultured with BMMs secreted exosomes into the medium and, compared with EPCs, exosomes had a higher expression level of LncRNA-MALAT1. We confirmed that LncRNA-MALAT1 directly binds to miR-124 to negatively control miR-124 activity. Moreover, overexpression of miR-124 could reverse the migration and osteoclastic differentiation of BMMs induced by EPC-derived exosomes. A dual-luciferase reporter assay indicated that the integrin ITGB1 is the target of miR-124. Mice treated with EPC-derived exosome-BMM co-transplantations exhibited increased neovascularization at the fracture site and enhanced fracture healing compared with those treated with BMMs alone. Overall, our results suggest that EPC-derived exosomes can promote bone repair by enhancing recruitment and differentiation of osteoclast precursors through LncRNA-MALAT1.