Degenerative changes of the canine cervical spine after discectomy procedures, an in vivo study.

BACKGROUND: Discectomies are a common surgical treatment for disc herniations in the canine spine. However, the effect of these procedures on intervertebral disc tissue is not fully understood. The objective of this study was to assess degenerative changes of cervical spinal segments undergoing discectomy procedures, in vivo. RESULTS: Discectomies led to a 60% drop in disc height and 24% drop in foraminal height. Segments did not fuse but showed osteophyte formation as well as endplate sclerosis. MR imaging revealed terminal degenerative changes with collapse of the disc space and loss of T2 signal intensity. The endplates showed degenerative type II Modic changes. Quantitative MR imaging revealed that over 95% of Nucleus Pulposus tissue was extracted and that the nuclear as well as overall disc hydration significantly decreased. Histology confirmed terminal degenerative changes with loss of NP tissue, loss of Annulus Fibrosus organization and loss of cartilage endplate tissue. The bony endplate displayed sclerotic changes. CONCLUSION: Discectomies lead to terminal degenerative changes. Therefore, these procedures should be indicated with caution specifically when performed for prophylactic purposes.

Detection of abnormalities in the superficial zone of cartilage repaired using a tissue engineered construct derived from synovial stem cells.

The present study investigated the surface structure and mechanical properties of repair cartilage generated from a tissue engineered construct (TEC) derived from synovial mesenchymal stem cells at six months post-implantation compared to those of uninjured cartilage. TEC-mediated repair tissue was cartilaginous with Safranin O staining, and had comparable macro-scale compressive properties with uninjured cartilage. However, morphological assessments revealed that the superficial zone of TEC-mediated tissue was more fibrocartilage-like, in contrast to the middle or deep zones that were more hyaline cartilage-like with Safranin O staining. Histological scoring of the TEC-mediated tissue was significantly lower in the superficial zone than in the middle and deep zones. Scanning electron microscopy showed a thick tangential bundle of collagen fibres at the most superficial layer of uninjured cartilage, while no corresponding structure was detected at the surface of TEC-mediated tissue. Immunohistochemical analysis revealed that PRG4 was localised in the superficial area of uninjured cartilage, as well as the TEC-mediated tissue. Friction testing showed that the lubrication properties of the two tissues was similar, however, micro-indentation analysis revealed that the surface stiffness of the TEC-repair tissue was significantly lower than that of uninjured cartilage. Permeability testing indicated that the TEC-mediated tissue exhibited lower water retaining capacity than did uninjured cartilage, specifically at the superficial zone. Thus, TEC-mediated tissue exhibited compromised mechanical properties at the superficial zone, properties which need improvement in the future for maintenance of long term repair cartilage integrity.

Efficacy of lumbar orthoses after posterior lumbar interbody fusion-a prospective randomized study.

BACKGROUND: Lumbosacral orthoses (LSOs) are used as standard care after lumbar fusion surgery though their efficacy is unknown. The purpose of this prospective randomized controlled study was to elucidate the clinical and radiographic efficacies of LSO treatment in patients who underwent posterior lumbar interbody fusion (PLIF) of less than 3 segments. METHODS: Seventy-three patients who underwent PLIF were randomly allocated to 3 groups: 1 with custom-made LSO with metallic stays (C group); 1 with ready-made LSO without metallic stays (R group), and 1 without LSO (N group). The patients in the C and R groups were instructed to wear LSO postoperatively for 3 months. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) score, JOA-back pain evaluation questionnaire (JOABPEQ), Roland-Morris Disability Questionnaire, and 100-mm visual analog scale for low back pain. Radiographic evaluation included intervertebral fusion rates and loss of correction postoperatively at 2 years. RESULTS: A significant difference in the clinical outcomes was observed only for the lumbar dysfunction domain of JOABPEQ postoperatively at 1 month (N vs C groups; 45% vs 10%, P = .03). Radiographic outcomes were not different between the groups. CONCLUSIONS: No effect of orthosis treatment for less than 3 segments in PLIF was observed on clinical and radiographic outcomes. The type of orthosis also did not influence the outcomes. These results suggest that the use of LSO for PLIF can be simplified or is omissible except in patients with severe osteoporosis.

Intervertebral disc regeneration with an adipose mesenchymal stem cell-derived tissue-engineered construct in a rat nucleotomy model.

Low back pain results in more global disabilities than any other condition, and intervertebral disc (IVD) degeneration is commonly involved in the etiology. Supplementation of IVDs with reparative cells is a rational strategy to address such clinical problems. We have previously developed a scaffold-free tissue-engineered construct (TEC) as a novel cell therapy system for repair of articular cartilage and meniscus. We now show the regenerative potential of adipose mesenchymal stem cells derived TEC (ADSC-TEC) for IVD degeneration using a rat tail model of total nucleotomy. The regenerative efficacy of ASDC-TEC was investigated structurally and biomechanically up to 6 months after implantation. ADSC-TEC implantation into IVDs preserved the disc height, endplate, and annulus fibrosus structure, and showed similar biomechanical characteristics to the sham group at postoperative 6 weeks. The structure of regenerated IVD was maintained until 6 months. Furthermore, ADSC-TEC implantation attenuated the impact of age-related biomechanical deterioration when assessed at 6 months post-implantation. These results demonstrate that use of ADSC-TECs can be an effective treatment for IVD degeneration. STATEMENT OF SIGNIFICANCE: We developed adipose mesenchymal stem cell-derived scaffold-free tissue engineered construct (ADSC-TEC) as a novel cell therapy system. The ADSC-TEC implantation into a rat total-nucleotomized disc space regenerated intervertebral discs (IVDs) histologically and biomechanically. The regenerative capacity of the ADSC-TEC was exerted by its trophic effects on annulus fibrosus cells and the load-sharing effect at intervertebral space. Interestingly, the regenerated IVDs by the ADSC-TEC was less susceptible to the age-related deterioration than the IVDs of normal rats. Thus, the application of ADSC-TEC into the degenerated disc can be an alternative therapy for various disease associated with structural and functional failure of IVDs.

Impact of Cervical Sagittal Alignment on Axial Neck Pain and Health-related Quality of Life After Cervical Laminoplasty in Patients With Cervical Spondylotic Myelopathy or Ossification of the Posterior Longitudinal Ligament: A Prospective Comparative Study.

STUDY DESIGN: This is prospective observational study. OBJECTIVE: To prospectively investigate the correlation among axial neck pain; a newly developed patient-based quality of life outcome measure, the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ); and cervical sagittal alignment after open-door laminoplasty for cervical myelopathy. SUMMARY OF BACKGROUND DATA: Many studies have focused on postoperative axial neck pain after laminoplasty. However, the correlation among cervical sagittal alignment, neck pain, and JOACMEQ has not been investigated. MATERIALS AND METHODS: In total, 57 consecutive patients treated by open-door laminoplasty for cervical myelopathy were included (mean age, 63.7 y; 15 women and 42 men) and divided into 2 groups according to diagnosis [cervical spondylotic myelopathy (CSM) group: 35 patients, and ossification of the posterior longitudinal ligament (OPLL) group: 22 patients]. JOA score, a subdomain of cervical spine function (CSF) in the JOACMEQ, and the visual analog scale for axial neck pain were assessed preoperatively and 12 months postoperatively. Radiographic cervical sagittal parameters were measured by C2 sagittal vertical axis (C2 SVA), C2-C7 lordosis, C7 sagittal slope (C7 slope), and range of motion. RESULTS: C2 SVA values in both groups shifted slightly anteriorly between preoperative and 12-month postoperative measurements (CSM: +19.7±10.9 mm; OPLL: +22.1±13.4 mm vs. CSM: +23.2±16.1 mm; OPLL: +28.7±15.4 mm, respectively). Postoperative axial neck pain in the OPLL group showed strong negative correlations with C2 SVA and C7 slope. Strong negative correlations were found between axial neck pain and CSF in both the preoperative CSM and OPLL groups (CSM: r=-0.45, P=0.01; OPLL: r=-0.61, P<0.01) and between axial neck pain and CSF in the postoperative OPLL group (r=-0.51, P=0.05). CONCLUSIONS: This study demonstrated a significant negative correlation between neck pain and CSF in both the CSM and OPLL groups preoperatively and in the OPLL group postoperatively. Radiographic cervical sagittal alignment did not significantly correlate with preoperative or postoperative axial neck pain.

Impact of non-thermal plasma surface modification on porous calcium hydroxyapatite ceramics for bone regeneration.

In the physiochemical sciences, plasma is used to describe an ionized gas. Previous studies have implicated plasma surface treatment in the enhancement of hydrophilicity of implanted musculoskeletal reconstructive materials. Hydroxyapatite (HA) ceramics, widely used in bone tissue regeneration, have made great advancements to skeletal surgery. In the present study, we investigate the impact of low-pressure plasma on the interconnected porous calcium hydroxyapatite (IP-CHA) both in vitro and in vivo. Our results indicate that dielectric barrier discharge (DBD) plasma, when used with oxygen, can augment the hydrophilicity of non-porous HA surfaces and the osteoconductivity of the IP-CHA disc via increased water penetration of inner porous structures, as demonstrated through microfocus computed tomography (µCT) assay. In vivo implantation of plasma-treated IP-CHA displayed superior bone ingrowth than untreated IP-CHA. Though plasma-treated IP-CHA did not alter osteoblast cell proliferation, it accelerated osteogenic differentiation of seeded marrow mesenchymal stem cells. In vitro X-ray photoelectron spectroscopy (XPS) revealed that this plasma treatment increases levels of oxygen, rather than nitrogen, on the plasma-treated IP-CHA surface. These findings suggest that plasma treatment, an easy and simple processing, can significantly improve the osteoconductive potential of commonly used artificial bones such as IP-CHA. Further optimization of plasma treatment and longer-term follow-up of in vivo application are required toward its clinical application.

The Impact of Cage Dimensions, Positioning, and Side of Approach in Extreme Lateral Interbody Fusion.

STUDY DESIGN: This is a retrospective single-center study. OBJECTIVE: The aim of the study was to evaluate the impact of cage characteristics and position toward clinical and radiographic outcome measures in patients undergoing extreme lateral interbody fusion (ELIF). SUMMARY OF BACKGROUND DATA: ELIF is utilized for indirect decompression and minimally invasive surgical treatment for various degenerative spinal disorders. However, evidence regarding the influence of cage characteristics in patient outcome is minimal. MATERIALS AND METHODS: Patients undergoing ELIF between 2007 and 2011 were included in a retrospective study. Demographic and perioperative data, as well as cage characteristics and side of approach were extracted. Radiographic parameters including lumbar lordosis, foraminal height, and disc height as well as clinical outcome parameters (Oswestry Disability Index and Visual Analog Scale) were measured preoperatively, postoperatively, and at the latest follow-up examination. Cage dimensions, in situ position, and type were correlated with radiographic and clinical outcome parameters. RESULTS: In total, 84 patients with a total of 145 functional spinal units were analyzed. At the last follow-up of 17.7 months, radiographic and clinical outcome measures revealed significant improvement compared with before surgery with both, 18 and 22 mm cage anterior-posterior diameter subgroups (P≤0.05). Among cage characteristics, 22 mm cages presented superior restoration of foraminal and disc heights compared with 18 mm cages (P≤0.05). Neither position of the cage (anterior vs. posterior), nor the type (parallel vs. lordotic) had a significant impact on restoration of foraminal height and lumbar lordosis. Moreover, the side of surgical approach did not influence the amount of foraminal height increase. CONCLUSIONS: Cage anterior-posterior diameter is the determining factor in restoration of foraminal height in ELIF. Cage height, type, positioning, and side of approach do not have a determining role in radiographic outcome in the present study. Sustainable foraminal height restoration is achieved by implantation of wider cages. LEVEL OF EVIDENCE: Level 3.

Time-Dependent Recovery of Human Synovial Membrane Mesenchymal Stem Cell Function After High-Dose Steroid Therapy: Case Report and Laboratory Study.

BACKGROUND: The use of mesenchymal stem cells from various tissue sources to repair injured tissues has been explored over the past decade in large preclinical models and is now moving into the clinic. PURPOSE: To report the case of a patient who exhibited compromised mesenchymal stem cell (MSC) function shortly after use of high-dose steroid to treat Bell's palsy, who recovered 7 weeks after therapy. STUDY DESIGN: Case report and controlled laboratory study. METHODS: A patient enrolled in a first-in-human clinical trial for autologous implantation of a scaffold-free tissue engineered construct (TEC) derived from synovial MSCs for chondral lesion repair had a week of high-dose steroid therapy for Bell's palsy. Synovial tissue was harvested for MSC preparation after a 3-week recovery period and again at 7 weeks after therapy. RESULTS: The MSC proliferation rates and cell surface marker expression profiles from the 3-week sample met conditions for further processing. However, the cells failed to generate a functional TEC. In contrast, MSCs harvested at 7 weeks after steroid therapy were functional in this regard. Further in vitro studies with MSCs and steroids indicated that the effect of in vivo steroids was likely a direct effect of the drug on the MSCs. CONCLUSION: This case suggests that MSCs are transiently compromised after high-dose steroid therapy and that careful consideration regarding timing of MSC harvest is critical. CLINICAL RELEVANCE: The drug profiles of MSC donors and recipients must be carefully monitored to optimize opportunities to successfully repair damaged tissues.

Annulus Fibrosus Repair Using High-Density Collagen Gel: An In Vivo Ovine Model.

STUDY DESIGN: Ovine in vivo study. OBJECTIVE: To perform lateral approach lumbar surgery in an ovine model to administer an injectable riboflavin cross-linked high-density collagen (HDC) gel and to assess its ability to mitigate intervertebral disc (IVD) degeneration after induced annulus fibrosus (AF) injury. SUMMARY OF BACKGROUND DATA: Biological-based injectable gels have shown efficacy in restoring biomechanical, radiographic, and histological parameters in IVD-injured animal models. Riboflavin cross-linked HDC gel has previously demonstrated retention of nucleus pulposus (NP) tissue, reduced loss of disc height, and prevention of terminal cellular degenerative changes in rat-tail spines. However, this biological therapy has never been tested in large animal models. METHODS: Forty lumbar IVDs were accessed from eight sheep via lateral approach surgery. IVDs were randomly assigned to healthy control, injury and HDC treatment, or negative control with injury and no treatment. IVD injury was carried out using a drill-bit through the AF followed by needle puncture of the NP. Sheep were followed for 16 weeks and underwent qualitative/quantitative magnetic resonance imaging, x-ray, and histological analyses of collagen and proteoglycan content. RESULTS: The lateral approach to the ovine lumbar spine to deliver HDC gel proved to be safe and reproducible. IVDs treated with the HDC gel revealed less degenerative changes at the microscopic level based on AF and NP histology. However, mean Pfirrmann grade, T2 relaxation time, NP voxel size, and disc height index were not significantly different between the two injury groups. CONCLUSION: Injectable HDC gel can be administered safely via lateral approach surgery in an ovine AF injury model. IVDs treated with HDC gel demonstrated less degeneration at the microscopic level though radiographic changes were slight when comparing treated to untreated IVDs. Future studies will need to elucidate the role of injury technique and time frame for follow-up in correlating histological and radiographical outcomes. LEVEL OF EVIDENCE: N /A.

In vivo annular repair using high-density collagen gel seeded with annulus fibrosus cells.

OBJECTIVE: The aim is assessing the in vivo efficacy of annulus fibrosus (AF) cells seeded into collagen by enhancing the reparative process around annular defects and preventing further degeneration in a rat-tail model. SUMMARY OF BACKGROUND DATA: Treating disc herniation with discectomy may relieve the related symptoms but does not address the underlying pathology. The persistent annular defect may lead to re-herniation and further degeneration. We recently demonstrated that riboflavin crosslinked high-density collagen gels (HDC) can facilitate annular repair in vivo. METHODS: 42 rats, tail disc punctured with an 18-gauge needle, were divided into 3 groups: untreated (n = 6), injected with crosslinked HDC (n = 18), and injected with AF cell-laden crosslinked HDC (n = 18). Ovine AF cells were mixed with HDC gels prior to injection. X-rays and MRIs were conducted over 5 weeks, determining disc height index (DHI), nucleus pulposus (NP) size, and hydration. Histological assessments evaluated the viability of implanted cells and degree of annular repair. RESULTS: Although average DHIs of both HDC gel groups were higher than those of the puncture control group at 5 weeks, the retention of disc height, NP size and hydration at 1 and 5 weeks was significant for the cellular group compared to the punctured, and at 5 weeks to the acellular group. Histological assessment indicated that AF cell-laden HDC gels have accelerated reparative sealing compared to acellular HDC gels. CONCLUSIONS: AF cell-laden HDC gels have the ability of better repairing annular defects than acellular gels after needle puncture. STATEMENT OF SIGNIFICANCE: This project addresses the compelling demand of a sufficient treatment strategy for degenerative disc disease (DDD) perpetuated by annulus fibrosus (AF) injury, a major cause of morbidity and burden to health care systems. Our study is designed to answer the question of whether injectable, photo-crosslinked, high density collagen gels can seal defects in the annulus fibrosus of rats and prevent disc degeneration. Furthermore, we investigated whether the healing of AF defects will be enhanced by the delivery of AF cells (fibrochondrocytes) to these defects. The use of cell-laden collagen gels in spine surgery holds promise for a wide array of applications, from current discectomy procedures to future nucleus pulposus reparative therapies, and our group is excited about this potential.

First-in-Human Pilot Study of Implantation of a Scaffold-Free Tissue-Engineered Construct Generated From Autologous Synovial Mesenchymal Stem Cells for Repair of Knee Chondral Lesions.

BACKGROUND: Articular cartilage has limited healing capacity, owing in part to poor vascularity and innervation. Once injured, it cannot be repaired, typically leading to high risk for developing osteoarthritis. Thus, cell-based and/or tissue-engineered approaches have been investigated; however, no approach has yet achieved safety and regenerative repair capacity via a simple implantation procedure. PURPOSE: To assess the safety and efficacy of using a scaffold-free tissue-engineered construct (TEC) derived from autologous synovial membrane mesenchymal stem cells (MSCs) for effective cartilage repair. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Five patients with symptomatic knee chondral lesions (1.5-3.0 cm2) on the medial femoral condyle, lateral femoral condyle, or femoral groove were included. Synovial MSCs were isolated from arthroscopic biopsy specimens and cultured to develop a TEC that matched the lesion size. The TECs were then implanted into chondral defects without fixation and assessed up to 24 months postoperatively. The primary outcome was the safety of the procedure. Secondary outcomes were self-assessed clinical scores, arthroscopy, tissue biopsy, and magnetic resonance image-based estimation of morphologic and compositional quality of the repair tissue. RESULTS: No adverse events were recorded, and self-assessed clinical scores for pain, symptoms, activities of daily living, sports activity, and quality of life were significantly improved at 24 months after surgery. Secure defect filling was confirmed by second-look arthroscopy and magnetic resonance imaging in all cases. Histology of biopsy specimens indicated repair tissue approaching the composition and structure of hyaline cartilage. CONCLUSION: Autologous scaffold-free TEC derived from synovial MSCs may be used for regenerative cartilage repair via a sutureless and simple implantation procedure. Registration: 000008266 (UMIN Clinical Trials Registry number).

Acute adrenal crisis after orthopedic surgery for pathologic fracture.

BACKGROUND: Adrenal crisis after surgical procedure is a rare but potentially catastrophic life-threatening event. Its manifestations, such as hypotension, tachycardia, hypoxia, and fever mimic the other more common postoperative complications. Clinical outcome is dependent upon early recognition of the condition and proper management with exogenous steroid administration. CASE PRESENTATION: We report a 75-year-old man who presented with shock immediately after surgery for a femoral fracture from lung cancer metastasis. Anemia and severe hyponatremia were detected. Despite adequate fluid resuscitation, nonspecific symptoms including hypotension, tachycardia, hypoxia, fever and confusion occurred. Emergent CT revealed enlarged bilateral adrenal glands. Under the diagnosis of adrenal crisis due to metastatic infiltration of adrenal glands, the patient was treated with appropriate steroid replacement resulting in rapid improvement and recovery. CONCLUSION: We describe a case of adrenal crisis caused by the lack of adrenal reserve based on metastatic involvement and surgical stress, the first published case of adrenal crisis after surgery for a pathologic fracture from lung cancer metastasis. Surgeons treating pathologic fractures should be aware of this complication and familiar with its appropriate therapy because of increasing opportunity to care patients with metastatic bone tumors due to recent advances in cancer treatment.

Comparison of 2 Different Formulations of Artificial Bone for a Hybrid Implant With a Tissue-Engineered Construct Derived From Synovial Mesenchymal Stem Cells: A Study Using a Rabbit Osteochondral Defect Model.

BACKGROUND: Previously, we developed a hybrid implant composed of hydroxyapatite (HA)-based artificial bone coupled with a mesenchymal stem cell (MSC)-based scaffold-free tissue-engineered construct (TEC) and demonstrated its feasibility for osteochondral repair. Beta-tricalcium phosphate (ßTCP) may be a promising alternative to HA, as it is a highly biocompatible material and is resorbed more rapidly than HA in vivo. HYPOTHESIS: A ßTCP-based hybrid TEC implant will exhibit superior osteochondral repair when directly compared with an HA-based hybrid implant, as tested using a rabbit osteochondral defect model. STUDY DESIGN: Controlled laboratory study. METHODS: Osteochondral defects were created in the femoral groove of skeletally mature rabbits. The TEC and artificial bone, using either HA or ßTCP with the same porosities and similar mechanical properties, were hybridized and then implanted in the defects. A histological evaluation and microindentation testing were performed for the assessment of repair tissue. RESULTS: Osteochondral defects treated with the TEC/ßTCP implants showed more rapid subchondral bone repair at 1 month, but the cartilaginous tissue deteriorated over time out to 6 months after implantation. Osteochondral defects treated with the TEC/HA implants maintained good histological quality out to 6 months after implantation and also exhibited better biomechanical properties at 6 months as compared with the TEC/ßTCP implants. CONCLUSION: Contrary to our hypothesis, the TEC/HA hybrid implant facilitated better osteochondral repair than did the TEC/ßTCP implant. The results of the present study suggest the importance of a stable restoration of subchondral bone for long-term effective osteochondral repair rather than rapid remodeling of subchondral bone. CLINICAL RELEVANCE: This study contributes to the future selection of suitable materials for patients with osteochondral lesions.

Total disc replacement using tissue-engineered intervertebral discs in the canine cervical spine.

The most common reason that adults in the United States see their physician is lower back or neck pain secondary to degenerative disc disease. To date, approaches to treat degenerative disc disease are confined to purely mechanical devices designed to either eliminate or enable flexibility of the diseased motion segment. Tissue engineered intervertebral discs (TE-IVDs) have been proposed as an alternative approach and have shown promise in replacing native IVD in the rodent tail spine. Here we demonstrate the efficacy of our TE-IVDs in the canine cervical spine. TE-IVD components were constructed using adult canine annulus fibrosis and nucleus pulposus cells seeded into collagen and alginate hydrogels, respectively. Seeded gels were formed into a single disc unit using molds designed from the geometry of the canine spine. Skeletally mature beagles underwent discectomy with whole IVD resection at levels between C3/4 and C6/7, and were then divided into two groups that received only discectomy or discectomy followed by implantation of TE-IVD. Stably implanted TE-IVDs demonstrated significant retention of disc height and physiological hydration compared to discectomy control. Both 4-week and 16-week histological assessments demonstrated chondrocytic cells surrounded by proteoglycan-rich matrices in the NP and by fibrocartilaginous matrices in the AF portions of implanted TE-IVDs. Integration into host tissue was confirmed over 16 weeks without any signs of immune reaction. Despite the significant biomechanical demands of the beagle cervical spine, our stably implanted TE-IVDs maintained their position, structure and hydration as well as disc height over 16 weeks in vivo.

Characterization of Mesenchymal Stem Cell-Like Cells Derived From Human iPSCs via Neural Crest Development and Their Application for Osteochondral Repair.

Mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iPSCs) are a promising cell source for the repair of skeletal disorders. Recently, neural crest cells (NCCs) were reported to be effective for inducing mesenchymal progenitors, which have potential to differentiate into osteochondral lineages. Our aim was to investigate the feasibility of MSC-like cells originated from iPSCs via NCCs for osteochondral repair. Initially, MSC-like cells derived from iPSC-NCCs (iNCCs) were generated and characterized in vitro. These iNCC-derived MSC-like cells (iNCMSCs) exhibited a homogenous population and potential for osteochondral differentiation. No upregulation of pluripotent markers was detected during culture. Second, we implanted iNCMSC-derived tissue-engineered constructs into rat osteochondral defects without any preinduction for specific differentiation lineages. The implanted cells remained alive at the implanted site, whereas they failed to repair the defects, with only scarce development of osteochondral tissue in vivo. With regard to tumorigenesis, the implanted cells gradually disappeared and no malignant cells were detected throughout the 2-month follow-up. While this study did not show that iNCMSCs have efficacy for repair of osteochondral defects when implanted under undifferentiated conditions, iNCMSCs exhibited good chondrogenic potential in vitro under appropriate conditions. With further optimization, iNCMSCs may be a new source for tissue engineering of cartilage.

Are Locked Facets a Contraindication for Extreme Lateral Interbody Fusion?

BACKGROUND: Extreme lateral interbody fusion (ELIF) has gained popularity as a minimally invasive treatment allowing for indirect decompression of neural elements. However, evidence regarding the influence of facet degeneration (FD) and facet tropism (FT) toward indirect decompression is lacking. The aim of the study was to evaluate whether indirect decompression is impaired by FD and FT in patients undergoing ELIF. METHODS: Thirty-seven patients undergoing ELIF were included in a retrospective study. Radiographic parameters including disk height, segmental disk angle, foraminal area, FD, FT, and clinical outcome parameters (Oswestry Disability Index and Visual Analog Scale) were measured preoperatively and postoperatively. FD and FT were correlated with radiographic and clinical outcome parameters in order to determine predictors restricting indirect decompression. RESULTS: Thirty-seven patients with a total of 74 levels were analyzed. Clinical and radiographic outcome measures including central canal area (Δ = +17.2 mm2), mean disk height (Δ = +3 mm), and foraminal area (Δ = +9.9 mm2) revealed significant improvement compared with before surgery (P ≤ 0.05). Patients with severe FD (grade 4) were more likely to have FT ≥ 12 degrees (32.3%) than patients without/mild (grades 0 and 1; 10%) or moderate FD (grades 2 and 3; 13%), P ≤ 0.05. FD and FT did not affect disk height restoration, foraminal area, canal surface area, or clinical outcome measures (P ≥ 0.05). CONCLUSIONS: Indirect decompression of neural elements in ELIF is not impaired by FD and FT are not relative contraindications in patients undergoing ELIF.

Minimally Invasive Transforaminal Lumbar Interbody Fusion: Meta-analysis of the Fusion Rates. What is the Optimal Graft Material?

BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is an increasingly popular procedure with several potential advantages over traditional open TLIF. OBJECTIVE: The current study aimed to compare fusion rates of different graft materials used in MIS-TLIF, via meta-analysis of the published literature. METHODS: A Medline search was performed and a database was created including patient's type of graft, clinical outcome, fusion rate, fusion assessment modality, and duration of follow-up. Meta-analysis of the fusion rate was performed using StatsDirect software (StatsDirect Ltd, Cheshire, United Kingdom). RESULTS: A total of 1533 patients from 40 series were included. Fusion rates were high, ranging from 91.8% to 99%. The imaging modalities used to assess fusion were computed tomography scans (30%) and X-rays (70%). Comparison of all recombinant human bone morphogenetic protein (rhBMP) series with all non-rhBMP series showed fusion rates of 96.6% and 92.5%, respectively. The lowest fusion rate was seen with isolated use of autologous local bone (91.8%). The highest fusion rate was observed with combination of autologous local bone with bone extender and rhBMP (99.1%). The highest fusion rate without the use of BMP was seen with autologous local bone + bone extender (93.1%). The reported complication rate ranged from 0% to 35.71%. Clinical improvement was observed in all studies. CONCLUSION: Fusion rates are generally high with MIS-TLIF regardless of the graft material used. Given the potential complications of iliac bone harvesting and rhBMP, use of other bone graft options for MIS-TLIF is reasonable. The highest fusion rate without the use of rhBMP was seen with autologous local bone plus bone extender (93.1%).

Biological Treatment Approaches for Degenerative Disc Disease: A Review of Clinical Trials and Future Directions.

Biologic-based treatment strategies for musculoskeletal diseases have gained traction over the past 20 years as alternatives to invasive, costly, and complicated surgical interventions. Spinal degenerative disc disease (DDD) is among the anatomic areas being investigated among this group, notably due to its high incidence and functional debilitation. In this review, we report the literature encompassing the use of biologic-based therapies for DDD. Articles published between January 1995 and November 2015 were reviewed, with a subset meeting the primary and secondary inclusion criteria of clinical trial results that could be sub-classified into bimolecular, cell-based, or gene therapies, as well as studies investigating the utility of allogeneic and tissue-engineered intervertebral discs. Ongoing clinical trials that have not yet published results are also mentioned to present the current state of the field. This exciting area has demonstrated positive and encouraging results across multiple strategies; thus, future bimolecular and regenerative techniques and understanding will likely lead to an increase in the number of human clinical trials assessing these therapies.

Biological Treatment Approaches for Degenerative Disk Disease: A Literature Review of In Vivo Animal and Clinical Data.

STUDY DESIGN: Literature review. OBJECTIVE: Degenerative disk disease (DDD) has a negative impact on quality of life and is a major cause of morbidity worldwide. There has been a growing interest in the biological repair of DDD by both researchers and clinicians alike. To generate an overview of the recent progress in reparative strategies for the treatment of DDD highlighting their promises and limitations, a comprehensive review of the current literature was performed elucidating data from in vivo animal and clinical studies. METHODS: Articles and abstracts available in electronic databases of PubMed, Web of Science, and Google Scholar as of December 2014 were reviewed. Additionally, data from unpublished, ongoing clinical trials was retrieved from clinicaltrials.gov and available abstracts from research forums. Data was extracted from the most recent in vivo animal or clinical studies involving any of the following: (1) treatment with biomolecules, cells, or tissue-engineered constructs and (2) annulus fibrosus repair. RESULTS: Seventy-five articles met the inclusion criteria for review. Among these, 17 studies involved humans; 37, small quadrupeds; and 21, large quadrupeds. Findings from all treatments employed demonstrated improvement either in regenerative capacity or in pain attenuation, with the exception of one clinical study. CONCLUSION: Published clinical studies on cell therapy have reported encouraging results in the treatment of DDD and resultant back pain. We expect new data to emerge in the near future as treatments for DDD continue to evolve in parallel to our greater understanding of disk health and pathology.

Total 3D Airo® Navigation for Minimally Invasive Transforaminal Lumbar Interbody Fusion.

Introduction. A new generation of iCT scanner, Airo®, has been introduced. The purpose of this study is to describe how Airo facilitates minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). Method. We used the latest generation of portable iCT in all cases without the assistance of K-wires. We recorded the operation time, number of scans, and pedicle screw accuracy. Results. From January 2015 to December 2015, 33 consecutive patients consisting of 17 men and 16 women underwent single-level or two-level MIS-TLIF operations in our institution. The ages ranged from 23 years to 86 years (mean, 66.6 years). We treated all the cases in MIS fashion. In four cases, a tubular laminectomy at L1/2 was performed at the same time. The average operation time was 192.8 minutes and average time of placement per screw was 2.6 minutes. No additional fluoroscopy was used. Our screw accuracy rate was 98.6%. No complications were encountered. Conclusions. Airo iCT MIS-TLIF can be used for initial planning of the skin incision, precise screw, and cage placement, without the need for fluoroscopy. "Total navigation" (complete intraoperative 3D navigation without fluoroscopy) can be achieved by combining Airo navigation with navigated guide tubes for screw placement.