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1.  Diamond Nanogel-Embedded Contact Lenses Mediate Lysozyme-Dependent Therapeutic Release 
ACS Nano  2014;8(3):2998-3005.
Temporarily implanted devices, such as drug-loaded contact lenses, are emerging as the preferred treatment method for ocular diseases like glaucoma. Localizing the delivery of glaucoma drugs, such as timolol maleate (TM), can minimize adverse effects caused by systemic administration. Although eye drops and drug-soaked lenses allow for local treatment, their utility is limited by burst release and a lack of sustained therapeutic delivery. Additionally, wet transportation and storage of drug-soaked lenses result in drug loss due to elution from the lenses. Here we present a nanodiamond (ND)-embedded contact lens capable of lysozyme-triggered release of TM for sustained therapy. We find that ND-embedded lenses composed of enzyme-cleavable polymers allow for controlled and sustained release of TM in the presence of lysozyme. Retention of drug activity is verified in primary human trabecular meshwork cells. These results demonstrate the translational potential of an ND-embedded lens capable of drug sequestration and enzyme activation.
doi:10.1021/nn5002968
PMCID: PMC4004290  PMID: 24506583
nanomedicine; contact lens; nanodiamond; drug delivery; biomaterials
2.  Finite Element Analysis for Comparison of Spinous Process Osteotomies Technique with Conventional Laminectomy as Lumbar Decompression Procedure 
Yonsei Medical Journal  2014;56(1):146-153.
Purpose
The purpose of this study was to evaluate and compare the biomechanical behavior of the lumbar spine after posterior decompression with the spinous process osteotomy (SPiO) technique or the conventional laminectomy (CL) technique using a finite element (FE) model.
Materials and Methods
Three validated lumbar FE models (L2-5) which represented intact spine and two decompression models using SPiO and CL techniques at the L3-4 segment were developed. In each model, the ranges of motion, the maximal von Mises stress of the annulus fibrosus, and the intradiscal pressures at the index segment (L3-4) and adjacent segments (L2-3 and L4-5) under 7.5 Nm moments were analyzed. Facet contact forces were also compared among three models under the extension and torsion moments.
Results
Compared to the intact model, the CL and SPiO models had increased range of motion and annulus stress at both the index segment (L3-4) and the adjacent segments under flexion and torsion. However, the SPiO model demonstrated a reduced range of motion and annulus stress than the CL model. Both CL and SPiO models had an increase of facet contact force at the L3-4 segment under the torsion moment compared to that of the intact model. Under the extension moment, however, three models demonstrated a similar facet contact force even at the L3-4 model.
Conclusion
Both decompression methods lead to postoperative segmental instability compared to the intact model. However, SPiO technique leads to better segmental stability compared to the CL technique.
doi:10.3349/ymj.2015.56.1.146
PMCID: PMC4276748  PMID: 25510758
Lumbar spinal stenosis; spinous process osteotomies; conventional laminectomy; finite element model
3.  Biomechanical Analysis of Fusion Segment Rigidity Upon Stress at Both the Fusion and Adjacent Segments: A Comparison between Unilateral and Bilateral Pedicle Screw Fixation 
Yonsei Medical Journal  2014;55(5):1386-1394.
Purpose
The purpose of this study was to investigate the effects of unilateral pedicle screw fixation on the fusion segment and the superior adjacent segment after one segment lumbar fusion using validated finite element models.
Materials and Methods
Four L3-4 fusion models were simulated according to the extent of decompression and the method of pedicle screws fixation in L3-4 lumbar fusion. These models included hemi-laminectomy with bilateral pedicle screw fixation in the L3-4 segment (BF-HL model), total laminectomy with bilateral pedicle screw fixation (BF-TL model), hemi-laminectomy with unilateral pedicle screw fixation (UF-HL model), and total laminectomy with unilateral pedicle screw fixation (UF-TL model). In each scenario, intradiscal pressures, annulus stress, and range of motion at the L2-3 and L3-4 segments were analyzed under flexion, extension, lateral bending, and torsional moments.
Results
Under four pure moments, the unilateral fixation leads to a reduction in increment of range of motion at the adjacent segment, but larger motions were noted at the fusion segment (L3-4) in the unilateral fixation (UF-HL and UF-TL) models when compared to bilateral fixation. The maximal von Mises stress showed similar patterns to range of motion at both superior adjacent L2-3 segments and fusion segment.
Conclusion
The current study suggests that unilateral pedicle screw fixation seems to be unable to afford sufficient biomechanical stability in case of bilateral total laminectomy. Conversely, in the case of hemi-laminectomy, unilateral fixation could be an alternative option, which also has potential benefit to reduce the stress of the adjacent segment.
doi:10.3349/ymj.2014.55.5.1386
PMCID: PMC4108828  PMID: 25048501
Unilateral pedicle screw fixation; lumbar fusion surgery; adjacent segment degeneration; finite element model
4.  Osteoporotic profiles in elderly patients with symptomatic lumbar spinal canal stenosis 
Indian Journal of Orthopaedics  2012;46(3):279-284.
Background:
The osteoporosis and lumbar canal stenosis, in elderly patients are under diagnosed and under reported. We report a cross sectional study to demonstrate the osteoporotic profile in patients with lumbar spinal stenosis (LSS) and to determine the proportion of patients with LSS who need to be treated for osteoporosis.
Materials and Methods:
One hundred and six postmenopausal patients with symptomatic LSS were evaluated for osteoporotic profile, which included lumbar and hip bone mineral density (BMD), serum vitamin D concentration, bone resorption and formation markers. Demographic and disease related variables were analyzed to identify the association with the risk of osteoporosis or osteopenia. Statistical analysis used were multivariate logistic regression with a forward stepwise procedure.
Results:
Twenty-four patients (22.6%) had osteoporosis and 60 (56.6%) had osteopenia. Overall, 84 patients (79.2%) with symptomatic LSS had osteoporosis or osteopenia. Fifty-nine patients (55.6%) had hypovitaminosis D. All bone turnover makers [alkaline phosphatase, osteocalcin, urinary-N-terminal telopeptide (u-NTx)] were demonstrated to be within normal range. Only age was associated with the risk of osteoporosis or osteopenia in the hip region. In the lumbar spine, all variables were not associated with osteoporosis or osteopenia. 44 patients (41.5%) required treatment for osteoporosis as per risk factors for osteoporosis. According to the guidelines from the Health Insurance Review Agency, however, only 20 patients (18.8% required) qualified for reimbursement for osteoporosis medications.
Conclusions:
LSS is associated with osteopenia, osteoporosis, and hypovitaminosis D, which should prompt careful screening and treatment in cases of osteoporosis and osteoarthritis.
doi:10.4103/0019-5413.96379
PMCID: PMC3377137  PMID: 22719113
Bone mineral density; bone turnover marker; hypovitaminosis D; lumbar spinal stenosis; osteoporosis
5.  Delayed Spinal Epidural Hematoma after En Block Spondylectomy for Vertebral Ewing's Sarcoma 
Asian Spine Journal  2010;4(2):118-122.
We report here on a case of a 23-year-old male who received en block spondylectomy for a vertebral Ewing's sarcoma at our hospital. Nine days after surgery, he presented with severe back pain and motor weakness of the lower extremities. Based on the physical examination and the computed tomography scan, he was diagnosed with acute cauda equina syndrome that was caused by compression from an epidural hematoma. His neurological functions recovered after emergency evacuation of the hematoma. This case showed that extensive surgery for a malignant vertebral tumor has a potential risk of delayed epidural hematoma and acute cauda equina syndrome and this should be treated with emergency evacuation.
doi:10.4184/asj.2010.4.2.118
PMCID: PMC2996623  PMID: 21165315
Epidural hematoma; Ewing's sarcoma; Spine; En block spondylectomy
6.  Pulsed Electromagnetic Field Stimulates Cellular Proliferation in Human Intervertebral Disc Cells 
Yonsei Medical Journal  2010;51(6):954-959.
Purpose
The purpose of this study is to investigate the mechanism of cellular proliferation of electromagnetic field (EMF) on human intervertebral disc (IVD) cells.
Materials and Methods
Human IVD cells were cultured three-dimensionally in alginate beads. EMF was exposed to IVD cells with 650Ω, 1.8 millitesla magnetic flux density, 60 Hz sinusoidal wave. Cultures were divided into a control and EMF group. Cytotoxicity, DNA synthesis and proteoglycan synthesis were measured by MTT assay, [3H]-thymidine, and [35S]-sulfate incorporation. To detect phenotypical expression, reverse transcription-polymerase chain reactions (RT-PCR) were performed for aggrecan, collagen type I, and type II mRNA expression. To assess action mechanism of EMF, IVD cells were exposed to EMF with NG-Monomethyl-L-arginine (NMMA) and acetylsalicylic acid (ASA).
Results
There was no cytotoxicity in IVD cells with the EMF group in MTT assay. Cellular proliferation was observed in the EMF group (p < 0.05). There was no difference in newly synthesized proteoglycan normalized by DNA synthesis between the EMF group and the control. Cultures with EMF showed no significant change in the expression of aggrecan, type I, and type II collagen mRNA compared to the control group. Cultures with NMMA (blocker of nitric oxide) or ASA (blocker of prostaglandin E2) exposed to EMF demonstrated decreased DNA synthesis compared to control cultures without NMMA or ASA (p < 0.05).
Conclusion
EMF stimulated DNA synthesis in human IVD cells while no significant effect on proteoglycan synthesis and chondrogenic phenotype expressions. DNA synthesis was partially mediated by nitric oxide and prostaglandin E2. EMF can be utilized to stimulate proliferation of IVD cells, which may provide efficient cell amplification in cell therapy to degenerative disc disease.
doi:10.3349/ymj.2010.51.6.954
PMCID: PMC2995961  PMID: 20879066
Electromagnetic fields; intervertebral disc; nitric oxide; prostaglandin E2
7.  Multiple Levels of Lumbar Spondylolysis - A Case Report - 
Asian Spine Journal  2009;3(1):35-38.
We report here on an unusual case of multiple levels of asymmetric lumbar spondylolysis in a 19-year-old woman. The patient had severe low back pain of increasing intensity with lumbar instability, which was evident on the dynamic radiographs. MRI demonstrated the presence of abnormalities and the three dimensional CT scan revealed asymmetric complete spondylolysis at the left L2, L3 and L4 levels and the right L1, L2 and L3 levels. This case was treated surgically by posterior and posterolateral fusion at L2-3-4 with intersegmental fixation using pedicle screws and an auto iliac bone graft. The patient was relieved of her low back pain after the surgery.
doi:10.4184/asj.2009.3.1.35
PMCID: PMC2852035  PMID: 20404945
Lower back pain; Multiple spondylolysis; Fusion
8.  20-Year-Follow up of Treatment Using Spine Osteotomy and Halo-pelvic Traction for Tuberculous Kyphosis - A Case Report - 
Asian Spine Journal  2009;3(1):27-31.
A 23-year-old male whose medical history included tuberculous spondylitis presented with a kyphotic deformity and incomplete paraplegia of twenty days duration. Preoperative radiographs demonstrated a T12-L4 kyphotic Cobb's angle of 100° with a complete block showing on the lumbar myelogram at L4-5. The patient underwent anterior osteotomy and release. After the operation, a halo-pelvic apparatus was fit onto the patient, and distraction was begun. After distraction for 2 months, posterior osteotomy and release was performed for final correction, and distraction was maintained for another three weeks. Finally, the kyphotic deformity was corrected to a Cobb's angle of 62° from T12 to L4. Supplementary anterior fusion was done, and the apparatus was removed after consolidation of the fusion mass.
Even twenty years after correction of a tuberculous kyphosis, he had no neurological deterioration, and could work as a farmer using agricultural machines. Correction angle and sagittal balance were well maintained.
doi:10.4184/asj.2009.3.1.27
PMCID: PMC2852040  PMID: 20404943
Tuberculous kyphosis; Halo-pelvic traction; Spine osteotomy
9.  Risk Factors Associated with the Halo Phenomenon after Lumbar Fusion Surgery and its Clinical Significance 
Asian Spine Journal  2008;2(1):22-26.
Study Design
Retrospective study.
Purpose
First, to examine the association between bone mineral density (BMD) and the halo phenomenon, and second, to investigate risk factors predisposing to the halo phenomenon and its correlation with clinical outcomes.
Overview of Literature
The few in vivo studies regarding the relationship between pedicle screw stability and BMD have shown conflicting results.
Methods
Forty-four female patients who underwent spine fusion surgery due to spinal stenosis were included in this study. The halo phenomenon and fusion state were evaluated through plain radiographs performed immediately after surgery and through the final outpatient follow-up examination. BMD, osteoarthritis grade in the hip and knee joints, and surgical outcome were also evaluated.
Results
BMD was not related to the halo phenomenon, but age, absence of osteoarthritis in the knee, and non-union state were found to be significant risk factors for the halo phenomenon. However, the radiological halo phenomenon did not correlate with clinical outcome (visual analogue scale for back pain and leg pain).
Conclusions
The halo phenomenon is a simple phenomenon that can develop during follow-up after pedicle screw fixation. It does not influence clinical outcomes, and thus it is thought that hydroxyapatite coating screws, expandable screws, cement augmentation, and additional surgeries are not required, if their purpose is to prevent the halo phenomenon.
doi:10.4184/asj.2008.2.1.22
PMCID: PMC2857487  PMID: 20411138
Halo phenomenon; Pedicle screw; Bone mineral density

Results 1-9 (9)