Biomimetic vascularized adipose-derived mesenchymal stem cells bone-periosteum graft enhances angiogenesis and osteogenesis in a male rabbit spine fusion model.

Aims: Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration. Methods: A total of 24 male New Zealand white rabbits were divided into four groups according to the experimental materials. Allogenic adipose-derived mesenchymal stem cells (AMSCs) were cultured and seeded evenly in the collagen/chitosan sheet to form cell sheet as periosteum. Simultaneously, allogenic AMSCs were seeded onto alginate beads and were cultured to differentiate to endothelial-like cells to form vascularized bone construct (VBC). The cell sheet was wrapped onto VBC to create a vascularized bone-periosteum construct (VBPC). Four different experimental materials - acellular construct, VBC, non-vascularized bone-periosteum construct, and VBPC - were then implanted in bilateral L4-L5 intertransverse space. At 12 weeks post-surgery, the bone-forming capacities were determined by CT, biomechanical testing, histology, and immunohistochemistry staining analyses. Results: At 12 weeks, the VBPC group significantly increased new bone formation volume compared with the other groups. Biomechanical testing demonstrated higher torque strength in the VBPC group. Notably, the haematoxylin and eosin, Masson's trichrome, and immunohistochemistry-stained histological results revealed that VBPC promoted neovascularization and new bone formation in the spine fusion areas. Conclusion: The tissue-engineered VBPC showed great capability in promoting angiogenesis and osteogenesis in vivo. It may provide a novel approach to create a superior blood supply and nutritional environment to overcome the deficits of current artificial bone graft substitutes.

The Use of Ultrasonic Bone Scalpel (UBS) in Unilateral Biportal Endoscopic Spine Surgery (UBESS): Technical Notes and Outcomes.

STUDY DESIGN: Case Series and Technical Note, Objective: UBS has been extensively used in open surgery. However, the use of UBS during UBESS has not been reported in the literature. The aim of this study was to describe a new spinal surgical technique using an ultrasonic bone scalpel (UBS) during unilateral biportal endoscopic spine surgery (UBESS) and to report the preliminary results of this technique. METHODS: We enrolled patients diagnosed with lumbar spinal stenosis who underwent single-level UBESS. All patients were followed up for more than 12 months. A unilateral laminotomy was performed after bilateral decompression under endoscopy. We used the UBS system after direct visualization of the target for a bone cut. We evaluated the demographic characteristics, diagnosis, operative time, and estimated blood loss of the patients. Clinical outcomes included the visual analog scale (VAS), the Oswestry Disability Index (ODI), the modified MacNab criteria, and postoperative complications. RESULTS: A total of twenty patients (five males and fifteen females) were enrolled in this study. The mean follow-up period was 13.2 months (range 12-17 months). The VAS score, ODI, and modified MacNab criteria classification improved after the surgery. A minimal mean blood loss of 22.1 mL was noted during the operation. Only one patient experienced neuropraxia, which resolved within 2 weeks. There was no durotomy, iatrogenic pars fracture, or infection. CONCLUSIONS: In conclusion, our study represents the first report of the use of UBS during UBESS. Our findings demonstrate that this technique is safe and efficient, with improved clinical outcomes and minimal complications. These preliminary results warrant further investigation through larger clinical studies with longer follow-up periods to confirm the effectiveness of this technique in the treatment of lumbar spinal stenosis.

Does Direct Surgical Repair Benefit Pars Interarticularis Fracture? A Systematic Review and Meta-analysis.

BACKGROUND: Promising results have been shown in previous studies from direct pars interarticularis repair. These include Scott wiring, Buck repair, pedicle screw repair, and Morscher techniques. In addition, several minimally invasive techniques have been reported to show high union rates, low rates of implant failure and wound complications, shorter length of stay, a lower postoperative pain score with faster recovery, and minimal blood loss. OBJECTIVES: To compare the evidence on techniques for direct pars interarticularis repair. STUDY DESIGN: Systematic review and meta-analysis. SETTING: Review article. METHODS: We conducted a comprehensive search of databases to identify studies assessing outcomes of direct pars interarticularis defect repair. Two authors independently screened electronic search results, performed study selection, and extracted data for meta-analysis. Sensitivity and subgroup analyses were performed to assess risk of bias. RESULTS: Forty studies were included in the final analysis. Union rate was higher in the pedicle screw repair group (effect size [ES] 95%; 95% CI, 86% to 100%), followed by the Buck repair group (ES 93%; 95% CI, 86% to 98%), Scott wiring (ES 85%; 95% CI, 63% to 99%), and Morscher method group (ES 63%; 95% CI, 2% to 100%). Positive functional outcome was higher for the Morscher method (ES 91%; 95% CI, 86% to 96%), followed by the Buck repair group (ES 85%; 95% CI, 68% to 97%), pedicle screw repair (ES 84%; 95% CI, 59% to 99%) and Scott repair group (ES 80%; 95% CI, 60% to 95%). Complication rates were highest among the Scott repair group (ES 12%; 95% CI, 4% to 22%) and Morscher method group (ES 12%; 95% CI, 0% to 34%). LIMITATIONS: Heterogeneity of the included studies were noted. However, we performed sensitivity analyses from the available data to address this issue. CONCLUSION: Our results indicate that pedicle screw repair and Buck repair may be associated with a higher union rate and lower complication rates compared to the Scott repair and Morscher method. Ultimately, the choice of technique should be based on the surgeon's preference and experience.

Minimally Invasive Percutaneous Vertebroplasty for Thoracolumbar Instrumented Vertebral Fracture in Patients With Posterior Instrumentation.

BACKGROUND: The traditional treatment for an instrumented vertebral fracture involves removing the loosened pedicle screws and extending the posterior instrumentation cephaladly or caudally. There has been a recent trend of performing minimally invasive fluoroscopy-guided percutaneous vertebroplasty as a salvage procedure. OBJECTIVE: The aim of this study was to compare the outcomes of surgical interventions for instrumented vertebral fracture. STUDY DESIGN: Retrospective assessment. SETTING: All data came from Chang Gung Memorial Hospital, Taiwan. METHODS: We retrospectively reviewed 35 patients with an instrumented vertebral fracture who underwent fluoroscopy-guided percutaneous vertebroplasty (Group I, n = 16) or extension of the posterior instrumentation (Group II, n = 19). Demographic data were recorded. The operating time, amount of intraoperative blood loss, time to postoperative ambulation, and duration of hospital stay were also evaluated. The visual analog scale (VAS) score, kyphotic angle on radiological images, Kirkaldy-Willis functional score, complications, and revision surgery were evaluated at one week and one, 3, 6, and 12 months postoperatively. RESULTS: Group I had a shorter operating time (P < 0.001), less intraoperative blood loss (P < 0.001), earlier postoperative ambulation (P < 0.001), and a shorter hospital stay (P < 0.001). The mean VAS score improved significantly after surgery in both groups (P = 0.001). The postoperative kyphotic angle was better in Group II (P < 0.05). There was no significant between-group difference in the Kirkaldy-Willis functional score at the last follow-up (P = 0.91). There was no significant between-group difference in the need for revision surgery (Group I, n = 4; Group II, n = 5; P = 0.93). LIMITATION: This study is a retrospective cohort. CONCLUSIONS: Minimally invasive fluoroscopy-guided percutaneous vertebroplasty can be used as an alternative to extension of posterior instrumentation for instrumented vertebral fracture. It has several advantages, including a shorter operating time, earlier postoperative ambulation, less blood loss, and a shorter hospital stay. The clinical outcomes of these 2 treatment approaches were similar.

Cement Augmentation for Single-Level Osteoporotic Vertebral Compression Fracture: Comparison of Vertebroplasty With High-Viscosity Cement and Kyphoplasty.

BACKGROUND: Although the majority of available evidence suggests that vertebroplasty and kyphoplasty (KP) can relieve pain associated with vertebral compression fractures (VCFs) and improve function, evidence of clinical and radiographic outcome in highly viscous cement vertebroplasty (HVC) or KP for the treatment of VCFs is limited. The purpose of this study was to compare the clinical effects between HVC and KP in the treatment of single-level osteoporotic VCFs including radiographic and clinical outcomes. METHODS: From January 2017 to October 2018, 96 patients with single-level osteoporotic vertebral compression fracture who had undergone either KP or HVC surgery at our hospital were reviewed retrospectively, with at least 1 year follow-up. All patients were divided into the HVC group (n = 50) or the KP group (n = 46). Clinical data including clinical and radiologic evaluation results were performed pre- and postoperatively. RESULTS: The operation time of the HVC group (32.24 ± 10.08 minutes) was less than that of the KP group (40.76 ± 9.49 minutes), with significant differences. Compared with preoperative data, the visual analog scale scores, Oswestry disability index scores, vertebral body height, and local kyphotic angle were improved after surgery. There were no significant differences between the 2 groups in local kyphotic angle, vertebral body height, leakage rate of bone cement, and incidence of adjacent-level vertebra fracture. CONCLUSIONS: Restoring the vertebral height and local kyphotic angle corrections of HVC are similar with those of KP. Additionally, KP is not superior in the leakage rate of bone cement and incidence of adjacent-level vertebra fracture compared to HVC.

Surgical Outcomes for Upper Lumbar Disc Herniation: Decompression Alone versus Fusion Surgery.

Upper lumbar herniated intervertebral disc (HIVD), defined as L1-2 and L2-3 levels, presents with a lower incidence and more unfavorable surgical outcomes than lower lumbar levels. There are very few reports onthe appropriate surgical interventions for treating upper lumbar HIVD. This study aimed to evaluate the surgical outcome of decompression alone, when compared with spinal fusion surgery. A retrospective study involving a total of 7592 patients who underwent surgery due to HIVD in our institution was conducted. A total of 49 patients were included in this study: 33 patients who underwent decompression-only surgery and 16 patients who underwent fusion surgery. Demographic data, perioperative information, and functional outcomes were recorded. The visual analog scale (VAS) scores showed improvement in both groups postoperatively. The three-month postoperative Oswestry Disability Index score was significantly better in the fusion group. Additionally, 10 patients (76.9%) in the decompression group and 5 patients (83.3%) in the fusion group reported improvement in preoperative motor weakness. The final "satisfactory" rate was 66.7% in the decompression group and 93.8% in the fusion group (p = 0.034). The overall surgical outcomes of patients with upper lumbar HIVD were satisfactory in this study without any major complications. More reliable satisfactory rates and better functional scores at the three-month postoperative follow-up were reported in the fusion group.

Rational design of gelatin/nanohydroxyapatite cryogel scaffolds for bone regeneration by introducing chemical and physical cues to enhance osteogenesis of bone marrow mesenchymal stem cells.

Identification of key components in the chemical and physical milieu for directing osteogenesis is a requirement in the investigation of tissue engineering scaffolds for advancement of bone regeneration. In this study, we engineered different gelatin-based cryogels and studied the effect of nanohydroxyapatite (nHAP) and crosslinking agents on scaffold properties and its osteogenic response towards bone marrow stem cells (BMSCs). The cryogels examined are 5% gelatin and 5% gelatin/2.5% nHAP, crosslinked either with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) or glutaraldehyde (GA). We confirmed that nHAP or the crosslinking agent has no effects on scaffold pore size and porosity. Nonetheless, incorporation of nHAP increased mechanical strength, swelling ratio and degree of crosslinking, but decreased degradation rate. Cryogels crosslinked with EDC showed faster degradation and promoted osteogenic differentiation of BMSCs while those prepared from GA crosslinking promoted proliferation of BMSCs. Furthermore, osteogenic differentiation was always enhanced in the presence of nHAP irrespective of the culture medium (normal or osteogenic) used but osteogenic medium always provide a higher extent of osteogenic differentiation. Employing gelatin/nHAP cryogel crosslinked by EDC in a bioreactor for dynamic culture of BMSCs, cyclic compressive mechanical simulation was found to be beneficial for both cell proliferation and osteogenic differentiation. However, the optimum conditions for osteogenic differentiation and cell proliferation were found at 30% and 60% strain, respectively. We thus demonstrated that osteogenic differentiation of BMSCs could be tuned by taking advantages of chemical cues generated from scaffold chemistry or physical cues generated from dynamic cell culture in vitro. Furthermore, by combining the best cryogel preparation and in vitro cell culture condition for osteogenesis, we successfully employed in vitro cultured cryogel/BMSCs constructs for repair of rabbit critical-sized cranial bone defects.

Comparison of Percutaneous Endoscopic Surgery and Traditional Anterior Open Surgery for Treating Lumbar Infectious Spondylitis.

Minimally invasive surgery is becoming popular for treating spinal disorders. The advantages of percutaneous endoscopic debridement and drainage (PEDD) for infectious spondylitis include direct observation of the lesion, direct pus drainage, and earlier pain relief. We retrospectively reviewed 37 patients who underwent PEDD and 31 who underwent traditional anterior open debridement and interbody fusion with bone grafting from 2004 to 2012. The causative organisms were isolated from 30 patients (81.1%) following PEDD, and from 25 patients (80.6%) following open surgery (p = 0.48). Staphylococcus aureus was the most common pathogen (38.2%). In the PEDD group, blood loss (<50 mL versus 585 ± 428 mL, p < 0.001) was significantly lesser and the duration of hospitalization (24.4 ± 12.5 days versus 31.5 ± 14.6 days, p = 0.03) was shorter than that in the open surgery group. Serologically, there were significantly faster C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) normalization rates in the PEDD group (p < 0.001, p = 0.009, respectively). In the two-year follow-up radiographs, 26 out of 30 (86.7%) open surgery patients showed bony fusions of the infected segments. On the contrary, sclerotic change of the destructive endplates was observed and the motion of infected spinal segments was still preserved in the PEDD group. There was no significant difference in the change of sagittal profile, including primary correction gain, correction loss, and actual correction gain/loss. PEDD is an effective alternative option and should be considered prior to traditional extensive spinal surgery-particularly for patients with early-stage spinal infection or serious complicated medical conditions.

Engineered periosteum-bone biomimetic bone graft enhances posterolateral spine fusion in a rabbit model.

BACKGROUND CONTEXT: Bone marrow derived mesenchymal stem cells (BMSCs) and periosteum-derived cells (PDCs) have shown great viability in terms of osteogenic potential and have been considered the major cellular source for skeletal tissue engineering. Using a PDCs-impregnated cell sheet to surround a BMSCs-impregnated tricalcium phosphate (TCP) scaffold might create a periosteum-bone biomimetic bone graft substitute to enhance spine fusion. PURPOSE: The purpose of this study was to determine the feasibility of using this newly tissue-engineered biomimetic bone graft for posterolateral spine fusion. STUDY DESIGN/SETTING: This study design was based on an animal model using adult male New Zealand White rabbits. METHODS: New Zealand White rabbits underwent operation and were divided into three groups based on the experimental material implanted in the bilateral L4-L5 intertransverse space. Group 1 was BMSCs-free TCP wrapped in a PDCs-free cell sheet. Group 2 was BMSCs-loaded-TCP wrapped in a PDCs-free cell sheet. Group 3 was BMSCs-loaded-TCP wrapped in a PDCs-loaded cell sheet. After 12 weeks, six rabbits from each group were euthanized for computed tomography scanning, manual palpation, biomechanical testing, and histology. Each group had 12 radiographic fusion areas for analysis because the right and left intertransverse fusion areas were collected separately. RESULTS: Radiographic union of 12 fusion areas for groups 1, 2, and 3 was 0, 3, and 9, respectively. Group 3 had significantly higher fusion success than groups 1 and 2 (p<.001). Solid fusion of six fusion segments in each group by manual palpation was 0, 1, and 5, accordingly. Group 3 had a higher successful solid fusion rate than groups 1 and 2 (p=.005). The average maximal torques at failure were 727±136 N mm, 627±91 N mm, and 882±195 N mm for groups 1, 2, and 3, accordingly. The maximal torque was significantly higher in group 3 than in group 2 (p=.028). Histological evaluation verified that new bone regeneration were greater in the group 3 samples. CONCLUSIONS: The results indicated the potential of using a PDCs-impregnated cell sheet to surround the BMSCs-impregnated TCP scaffold for creating a periosteum-bone biomimetic bone graft substitute to enhance bone regeneration and posterolateral fusion success.

Appropriate duration of post-surgical intravenous antibiotic therapy for pyogenic spondylodiscitis.

BACKGROUND: Most guidelines recommend 6 to 12 weeks of parenteral antibiotic treatment for pyogenic spondylodiscitis. When surgical debridement is adequately performed, further intravenous antibiotic treatment duration can be reduced than that of conservative treatment alone theoretically. However, the appropriate duration of post-surgical parenteral antibiotic treatment is still unknown. This study aimed to identify the risk factors of recurrence and evaluate the appropriate duration after surgical intervention. METHODS: This 3-year retrospective review included 102 consecutive patients who were diagnosed with pyogenic spondylodiscitis and underwent surgical intervention. Recurrence was defined as recurrent signs and symptoms and the need for another unplanned parenteral antibiotic treatment or operation within one year. This study included two major portions. First, independent risk factors for recurrence were identified by multivariable analysis, using the database of demographic information, pre-operative clinical signs and symptoms, underlying illness, radiographic findings, laboratory tests, intraoperative culture results, and treatment. Patients with any one of the risk factors were considered high-risk; those with no risk factors were considered low-risk. Recurrence rates after short-term (≤3 weeks) and long-term (> 3 weeks) parenteral antibiotic treatment were compared between the groups. RESULTS: Positive blood culture and paraspinal abscesses were identified as independent risk factors of recurrence. Accordingly, 59 (57.8%) patients were classified as low-risk and 43 (42.2%) as high-risk. Among the high-risk patients, a significantly higher recurrence rate occurred with short-term than with long-term antibiotic therapy (56.2% vs. 22.2%, p = 0.027). For the low-risk patients, there was no significant difference between short-term and long-term antibiotic therapy (16.0% vs. 20.6%, p = 0.461). CONCLUSIONS: The appropriate duration of parenteral antibiotic treatment in patients with pyogenic spondylodiscitis after surgical intervention could be guided by the risk factors. The duration of postoperative intravenous antibiotic therapy could be reduced to 3 weeks for patients without positive blood culture or abscess formation.

The Preparation of Graphene Oxide-Silver Nanocomposites: the Effect of Silver Loads on Gram-Positive and Gram-Negative Antibacterial Activities.

In this work, silver nanoparticles (Ag NPs) were decorated on thiol (-SH) grafted graphene oxide (GO) layers to investigate the antibacterial activities in Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Pseudomonas aeruginosa). The quasi-spherical, nano-sized Ag NPs were attached to the GO surface layers, as confirmed by using field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM), respectively. The average size of GO-Ag nanocomposites was significantly reduced (327 nm) from those of pristine GO (962 nm) while the average size of loaded Ag NPs was significantly smaller than the Ag NPs without GO. Various concentrations of AgNO3 solutions (0.1, 0.2, and 0.25 M) were loaded into GO nanosheets and resulted in the Ag contents of 31, 43, and 65%, respectively, with 1-2 nm sizes of Ag NPs anchored on the GO layers. These GO-Ag samples have negative surface charges but the GO-Ag 0.2 M sample (43% Ag) demonstrated the highest antibacterial efficiency. At 10 ppm load of GO-Ag suspension, only a GO-Ag 0.2 M sample yielded slight bacterial inhibition (5.79-7.82%). As the GO-Ag content was doubled to 20 ppm, the GO-Ag 0.2 M composite exhibited ~49% inhibition. When the GO-Ag 0.2 M composite level was raised to 100 ppm, almost 100% inhibition efficiencies were found on both Staphylococcus aureus (S.A.) and Pseudomonas aeruginosa (P.A.), which were significantly higher than using pristine GO (27% and 33% for S.A. and P.A.). The combined effect of GO and Ag nanoparticles demonstrate efficient antibacterial activities.

Gelatin/Nanohyroxyapatite Cryogel Embedded Poly(lactic-co-glycolic Acid)/Nanohydroxyapatite Microsphere Hybrid Scaffolds for Simultaneous Bone Regeneration and Load-Bearing.

It is desirable to combine load-bearing and bone regeneration capabilities in a single bone tissue engineering scaffold. For this purpose, we developed a high strength hybrid scaffold using a sintered poly(lactic-co-glycolic acid) (PLGA)/nanohydroxyapatite (nHAP) microsphere cavity fitted with gelatin/nHAP cryogel disks in the center. Osteo-conductive/osteo-inductive nHAP was incorporated in 250⁻500 µm PLGA microspheres at 40% (w/w) as the base matrix for the high strength cavity-shaped microsphere scaffold, while 20% (w/w) nHAP was incorporated into gelatin cryogels as an embedded core for bone regeneration purposes. The physico-chemical properties of the microsphere, cryogel, and hybrid scaffolds were characterized in detail. The ultimate stress and Young's modulus of the hybrid scaffold showed 25- and 21-fold increases from the cryogel scaffold. In vitro studies using rabbit bone marrow-derived stem cells (rBMSCs) in cryogel and hybrid scaffolds through DNA content, alkaline phosphatase activity, and mineral deposition by SEM/EDS, showed the prominence of both scaffolds in cell proliferation and osteogenic differentiation of rBMSCs in a normal medium. Calcium contents analysis, immunofluorescent staining of collagen I (COL I), and osteocalcin (OCN) and relative mRNA expression of COL I, OCN and osteopontin (OPN) confirmed in vitro differentiation of rBMSCs in the hybrid scaffold toward the bone lineage. From compression testing, the cell/hybrid scaffold construct showed a 1.93 times increase of Young's modulus from day 14 to day 28, due to mineral deposition. The relative mRNA expression of osteogenic marker genes COL I, OCN, and OPN showed 5.5, 18.7, and 7.2 folds increase from day 14 to day 28, respectively, confirming bone regeneration. From animal studies, the rBMSCs-seeded hybrid constructs could repair mid-diaphyseal tibia defects in rabbits, as evaluated by micro-computed tomography (µ-CT) and histological analyses. The hybrid scaffold will be useful for bone regeneration in load-bearing areas.

Exposure of Prebiopsy Antibiotics Influence Bacteriological Diagnosis and Clinical Outcomes in Patients With Infectious Spondylitis.

The benefit of prebiopsy empirical antibiotics for patients with infectious spondylitis and the effect on clinical outcome are not well known. This study assessed the impact of prebiopsy empirical antibiotics in patients with infectious spondylitis. We retrospectively reviewed 41 adult in-patients with infectious spondylitis who received percutaneous endoscopic debridement and drainage (PEDD) at a tertiary care hospital from August 2002 to August 2012. The average patient age was 55.2 years old and causative bacteria were identified in 32 out of 41 biopsy specimens (78.0%) via the PEDD procedure, which has good diagnostic efficacy comparable to open biopsy. Seventeen patients (41.5%) received prebiopsy empirical antimicrobial therapy, and these patients were less likely to have positive cultures than those who did not receive preoperative antibiotics (64.7% vs 87.5%, P = 0.04). Patients with positive cultures had a better infection control rate (78.1% vs 67.7%) and were less likely to undergo subsequent open surgery. Patients given preoperative antibiotics were more likely to need subsequent open surgery (35.3% vs 16.7%, P = 0.02). From multivariate logistic analysis showed age at diagnosis to be an independent risk factor for the need of further surgery. There were no major complications following the PEDD procedure, except 2 patients had transient paresthesia in the affected lumbar segments. Prebiopsy empirical antibiotic therapy was associated with lower positive culture rate and an increased need for subsequent open surgery. Patients with positive cultures were more likely to have initially adequate treatment, better infection control, and better clinical outcome.

Mesenchymal stem cells expressing baculovirus-engineered BMP-2 and VEGF enhance posterolateral spine fusion in a rabbit model.

BACKGROUND CONTEXT: Mesenchymal stem cell (MSC)-based cell therapy and gene transfer have converged and show great potential for accelerating bone healing. Gene therapy can provide more sustained expression of osteogenic factors such as bone morphogenetic protein-2 (BMP-2). We previously demonstrated that low-dose BMP-2 enhanced spinal posterolateral fusion by MSCs in a rabbit model. Herein, we genetically modified rabbit MSCs with a recombinant baculovirus encoding BMP-2 (Bac-CB) and vascular endothelial growth factor (Bac-VEGF) seeded into porous scaffolds to enhance spinal fusion. PURPOSE: This study evaluates the success rate of the MSC-based cell therapy and gene transfer approach for single-level posterolateral spine fusion. We hypothesize that combining three-dimensional tricalcium phosphate (TCP) scaffolds and genetically modified allogeneic MSCs with baculovirus-mediated growth factor expression would increase the success rate of spinal fusion. STUDY DESIGN: The study design was based on an animal model (approved by the Institutional Animal Care and Use Committee) using 18 adult male New Zealand rabbits. METHODS: This study included 18 male New Zealand rabbits, weighing 3.5 to 4 kg. Allogeneic bone marrow-derived MSCs were isolated and genetically modified with Bac-CB and Bac-CV seeded onto TCP scaffolds (MSC/Bac/TCP). The animals were divided into three groups according to the material implanted into the bilateral L4-L5 intertransverse space: TCP scaffold (n=6), MSC/TCP (n=6), and MSC/Bac/TCP (n=6). After 12 weeks, the rabbits were euthanized for radiographic examination, manual palpation, and histologic study. RESULTS: Bilateral fusion areas in each animal were evaluated independently. The radiographic fusion rates at 12 sites were 0 of 12 in the TCP scaffold group, 4 of 12 in the MSC/TCP group, and 10 of 12 in the MSC/Bac/TCP group. By manual palpation, there were zero solid fusions in the TCP scaffold group, two solid fusions in the MSC/TCP group, and five solid fusions in the MSC/Bac/TCP group. Fusion rates were significantly greater in the MSC/Bac/TCP group. CONCLUSIONS: The results indicate the potential of using baculovirus as a vector for gene/cell therapy approaches to improve bone healing and support the feasibility of using allogeneic MSCs for inducing bone formation and intertransverse process fusion.

Enhancement of rotator cuff tendon-bone healing with injectable periosteum progenitor cells-BMP-2 hydrogel in vivo.

PURPOSE: The fixation and incorporation of ruptured rotator cuff tendon to bone is a major concern in rotator cuff repair surgery. Rotator cuff repair usually fails at the tendon-bone interface, especially in case of large or massive tears. To enhance tendon-bone healing, an injectable hydrogel made with periosteal progenitor cells(PPCs) and poly (ethylene glycol) diacrylate (PEGDA) tethered with bone morphogenic protein-2(BMP-2) was developed to encourage extracellular matrix synthesis for tendon-to-bone healing in rotator cuff repair. METHODS: The infraspinatus tendon was cut from the greater tuberosity and repaired through a transosseous tunnel with the injectable progenitor cell-BMP-2 hydrogel applied between the tendon-bone interface. The injectable hydrogel was prepared from 10% poly (ethylene glycol) diacrylate (PEGDA) containing 0.05% of the photoinitiator. BMP-2 tethered with poly(ethylene glycol) (PEG) was blended to the hydrogel. Rabbit periosteal progenitor cells (PPCs) isolated from periosteum were mixed with hydrogel and injected on the tendon-bone interface. Ultraviolet radiation (365 nm) was applied for 60 s to photopolymerize the injection and solidify the hydrogel. The rabbits were killed at 4 and 8 weeks. The morphological characteristics of the healing tendon-to-bone interface were evaluated by histological and immunohistochemical methods. The biomechanical test was done to determine healing attachment strength. RESULTS: At both the 4- and 8-week killing, histological analysis of the tendon-bone interface showed an increasing fibrocartilage and bone layer formed in the tendon-bone interface in PEGDA group. At 4 weeks, fibrocartilage-like tissue was observed in a focal area. At 8 weeks, further matrix deposition occurred with fibrocartilage formation in the tendon-bone junction, and bone formation appeared near host bone. Immunohistochemistry revealed the presence of aggrecan and type II collagen. Biomechanical testing revealed a higher maximum pull-out load at all time points with a statistically significant difference at 4 and 8 weeks postoperatively. CONCLUSION: PEGDA hydrogel was approved as an adequate matrix for the encapsulation of cells and signal factor, and as an effective local delivery method to the tendon-bone interface through injection and photopolymerization. The PPCs-BMP2-hydrogel provides a powerful inductive ability between the tendon and the bone and enhances tendon-bone healing through the neoformation of fibrocartilage.

Arthroscopic single-bundle anterior cruciate ligament reconstruction with periosteum-enveloping hamstring tendon graft: clinical outcome at 2 to 7 years.

PURPOSE: In this case-series outcome study, we present our surgical technique for single-bundle anterior cruciate ligament (ACL) reconstruction with periosteum-enveloping hamstring tendon graft at a minimum of 2 years' follow-up. METHODS: From 2000 to 2005, ACL reconstruction with a periosteum-enveloping hamstring tendon graft was performed in 368 patients (372 knees). Of those patients, 312 who completed at least 2 years of follow-up were included for analysis. Four-strand periosteum-enveloping hamstring tendon grafts were used for single-bundle reconstruction. Clinical assessments included the Lysholm knee score, International Knee Documentation Committee score, KT-1000 instrumented testing (MEDmetric, San Diego, CA), thigh muscle assessment, and radiographic evaluation. Radiographs were used to assess femoral and tibial tunnel widening. RESULTS: The 312 study patients were followed up for a mean of 4.6 years (range, 2 to 7 years). The median Lysholm knee scores were 56 points (range, 40 to 70 points) and 95 points (range, 60 to 100 points) before and after surgery, respectively. After reconstruction, 85% of patients could return to moderate or strenuous activity, 5.1% exhibited grade 2 or higher ligament laxity with the anterior drawer test, and 6.1% had a positive pivot shift. Complete range of motion was achieved in 88% of patients. On the basis of International Knee Documentation Committee assessment, 93% of patients had a normal or nearly normal rating. CONCLUSIONS: Satisfactory results can be achieved with the periosteum-enveloping hamstring tendon graft in single-bundle ACL reconstruction with minimal tunnel widening. Bone tunnel enlargement of more than 1 mm was identified in 5.4% of femoral tunnels and 6.1% of tibial tunnels, which was less than in other studies using comparable fixation. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Instrumented posterior lumbar interbody fusion for patients with degenerative lumbar scoliosis.

OBJECTIVE: Surgery for degenerative lumbar scoliosis remains challenging for spine surgeons even with the application of pedicle screw instrumentation. This retrospective study assesses the outcomes of instrumented posterior lumbar interbody fusion (PLIF) for degenerative lumbar scoliosis. METHODS: From April 2000 to April 2004, 26 patients with degenerative lumbar scoliosis were treated with instrumented PLIF. Mean age of the 15 females and 11 males was 64.2 years (range, 51 to 77 y). Clinical and radiographic outcomes were retrospectively reviewed for each case at a minimum follow-up of 2 years (median follow-up, 3 y; range, 2 to 6 y). At final follow-up, patients were classified as "satisfied" or "dissatisfied" according to self-reported outcomes. RESULTS: At most recent follow-up, the average Oswestry Disability Index score was significantly lower than the preoperative score (25.8 vs. 58.0; P<0.001). Twenty (76.9%) patients reported that they were satisfied with their surgical outcomes. The average lumbar scoliosis angles were significantly less than preoperative angles (7.4 vs. 16.5 degrees; P<0.001), resulting in a reduction in mean scoliosis angles of 55.2%. The average angles of lumbar lordosis were significantly higher than preoperative angles (30.1 vs. 22.2 degrees; P=0.001), an increase in mean lumbar lordosis angles of 35.6%. No perioperative deaths or major medical complications occurred. Five patients had adjacent segment degeneration and 4 (80%) of 5 reported dissatisfactory outcomes. Further study is required to identify the etiologies of adjacent segment degeneration and methods for avoiding such degeneration. CONCLUSIONS: Analytical results demonstrate that instrumented PLIF after laminectomy in patients with degenerative lumbar scoliosis is an effective and safe procedure.

Pedicle screw insertion: computed tomography versus fluoroscopic image guidance.

Computed tomography image-guided surgery (CTGS) clearly improves the accuracy of pedicle screw insertion. Recent reports claim that a fluoroscopy-guided system (FGS) offered high accuracy and easy application. However, the superiority of either technique remains unclear in clinical application. This study compares the accuracy of pedicle screws installed using CTGS with that of screws installed using FGS. Seventy-four screws inserted using FGS in 13 patients and 76 screws inserted using CTGS in 11 patients were compared. The study population included ten cases of vertebral fracture, five cases of degenerative spondylolisthesis, three cases of spondylolytic spondylolisthesis, two cases of tuberculous spondylitis, two cases of failed earlier back surgery and two case of ankylosing spondylitis with pseudarthrosis. The installed vertebral levels ranged from T8 to S1. Screw positions were assessed with postoperative radiographs and computed tomography. Sixty-nine (93.2%) screws were correctly placed in the FGS group, and seventy-three (96.1%) screws were correctly placed in the CTGS group (P=0.491). The results indicated that both image-guided systems offer high accuracy. However, the fluoroscope image-guided system could be considered the primary tool for lower thoracic and lumbosacral pedicle placement because it enables real-time navigation and does not require a preoperative CT scan.

Posterior decompression and stabilization for metastatic spine diseases.

BACKGROUND: The purpose of this study was to investigate the clinical results of posterior decompression and stabilization for metastatic diseases of the thoracolumbar spine. METHODS: From 1980 to 2001, 70 consecutive patients with spinal metastases underwent palliative surgery by posterior decompression of spinal cord and subsequent stabilization with instrumentation. There were 38 women and 32 men. Their ages ranged from 24 to 75 years (mean 58 years). We retrospectively reviewed medical records to analyze their survival, clinical presentations, image findings and surgical outcomes. RESULTS: Sixty-one patients (87%) survived longer than 3 months. Forty-nine patients (70%) survived longer than 6 months, of whom 35 patients were still alive at an average of 24 months (range 13-40 months) after surgery. All maintained spinal stability postoperatively. Forty-seven of 60 patients (78.3%) with severe pain obtained significant symptomatic relief for 3 months or more, and 38 of 54 (70.1%) paralyzed patients gained neural improvement. Of the 60 patients bedridden before surgery due to pain or paresis, 36 patients (60%) experienced an increase in activity tolerance. CONCLUSIONS: The results of this study shows that neurological recovery, pain relief and mobility can be enhanced by posterior decompression and stabilization in highly selective patients with spinal metastases.

Computer-assisted fluoroscopic navigation of pedicle screw insertion: an in vivo feasibility study.

BACKGROUND: Accurate placement of pedicle screws is difficult. PATIENTS AND METHODS: We evaluated the feasibility and accuracy of pedicle screw insertion assisted by a real-time, 2-dimensional (2D) image-guided navigation system in 12 patients who underwent thoraco-lumbar and/or lumbar stabilization. 66 pedicle screws were inserted either by senior spine surgeons or residents. The accuracy of positioning of the screws was evaluated using postoperative plain radiographs and thin-cut CT. RESULTS: 61 of the 66 screws were inserted successfully. 5 screw insertions showed structural violations: 4 on the medial and 1 on the lateral pedicle wall. The accuracy was higher in the sagittal plane than in the axial plain. There was no difference between the surgical error rates caused by the senior surgeons and the residents. INTERPRETATION: Using computer-assisted 2D fluoroscopic image navigation, it is possible to achieve reliable and accurate pedicle screw insertion during low thoracic and lumbar spinal surgery.