Keung Nyun Kim

The electron beam deposition of titanium on polyetheretherketone (PEEK) and the resulting enhanced biological properties

The surface of polyetheretherketone (PEEK) was coated with a pure titanium (Ti) layer using an electron beam (e-beam) deposition method in order to enhance its biocompatibility and adhesion to bone tissue. The e-beam deposition method was a low-temperature coating process that formed a dense, uniform and well crystallized Ti layer without deteriorating the characteristics of the PEEK implant. The Ti coating layer strongly adhered to the substrate and remarkably enhanced its wettability. The Ti-coated samples were evaluated in terms of their in vitro cellular behaviors and in vivo osteointegration, and the results were compared to a pure PEEK substrate. The level of proliferation of the cells (MC3T3-E1) was measured using a methoxyphenyl tetrazolium salt (MTS) assay and more than doubled after the Ti coating. The differentiation level of cells was measured using the alkaline phosphatase (ALP) assay and also doubled. Furthermore, the in vivo animal tests showed that the Ti-coated PEEK implants had a much higher bone-in-contact (BIC) ratio than the pure PEEK implants. These in vitro and in vivo results suggested that the e-beam deposited Ti coating significantly improved the potential of PEEK for hard tissue applications.

Artificial Disc Replacement Combined With Fusion versus Two-level Fusion in Cervical Two-level Disc Disease

Study Design. A prospective analysis. Objective. The purpose of this study was to compare the clinical and radiologic outcomes of cervical artificial disc replacement (C-ADR) combined with anterior cervical discectomy and fusion (ACDF) and 2-level ACDF in patients with 2-level cervical disc disease. Summary of Background Data. Adjacent segment degeneration is a long-term complication of ACDF, and estimated to affect 25% of patients within 10 years of the initial surgery. Two-level fusion leads to a substantially greater increase in intradiscal pressure than one-level fusion. It has been demonstrated that C-ADR maintains motion at the level of the surgical procedure and decreases strain on the adjacent segments for prevention of adjacent segment degeneration. In the case of 2-level cervical disc disease, hybrid surgery (HS), consisting of C-ADR combined with ACDF, may be a reasonable alternative to 2-level ACDF (2-ACDF). Methods. Between 2004 and 2006, 40 patients undergoing 2-level cervical disc surgery at our hospital were identified who met the following surgical indications: 2 consecutive level degenerative disc disease between C3/4 and C6/7; either a radiculopathy or myelopathy; and no response to conservative treatment for >6 weeks. Twenty patients of the HS group were matched to 20 patients of the 2-ACDF group based on age and gender. Patients were asked to check the neck disability index (NDI) and grade their pain intensity before surgery and at routine postoperative intervals of 1, 3, 6, 12, and 24 months. Dynamic flexion and extension lateral cervical radiographs were obtained in the standing position before surgery and at routine postoperative intervals of 1, 3, 6, 12, and 24 months. The angular range of motion (ROM) for C2–C7 and adjacent segments were measured using the Cobb method with PACS software. Results. The HS group had better NDI recovery 1 and 2 years after surgery (P < 0.05). Postoperative neck pain was less in the HS group 1 month and 1 year after surgery (P < 0.05). There was no difference in arm pain relief between the groups. The HS group showed faster C2–C7 ROM recovery. The mean C2–C7 ROM of the HS group recovered to that of the preoperative value, but that of the 2-ACDF group did not (P < 0.05). The inferior adjacent segment ROM showed significant differences between the groups 6 and 9 months, and 1 and 2 years after surgery (P < 0.05, P < 0.01, P < 0.05, and P < 0.05, respectively). Conclusion. HS is superior to 2-ACDF in terms of better NDI recovery, less postoperative neck pain, faster C2–C7 ROM recovery, and less adjacent ROM increase.

Postoperative Spinal Epidural Hematoma: Risk Factor and Clinical Outcome

We report a series of epidural hematomas which cause neurologic deterioration after spinal surgery, and have taken risk factors and prognostic factors into consideration. We retrospectively reviewed the database of 3720 cases of spine operation in a single institute over 7 years (1998 April-2005 July). Nine patients who demonstrated neurologic deterioration after surgery and required surgical decompression were identified. Factors postulated to increase the postoperative epidural hematoma and to improve neurologic outcome were investigated. The incidence of postoperative epidural hematoma was 0.24%. Operation sites were cervical 3 cases, thoracic 2 cases, and lumbar 4 cases. Their original diagnoses were tumor 3 cases, cervical stenosis 2 cases, lumbar stenosis 3 cases and herniated lumbar disc 1case. The symptoms of epidural hematomas were neurologic deterioration and pain. After decompression, clinical outcome revealed complete recovery in 3 cases (33.3%), incomplete recovery in 5 cases (55.6%) and no change in 1 case (11.1%). Factors increasing the risk of postoperative epidural hematoma were coagulopathy from medical illness or anticoagulation therapy (4 cases, 44.4%) and highly vascularized tumor (3 cases, 33.3%). The time interval to evacuation of complete recovery group (29.3 hours) was shorter than incomplete recovery group (66.3 hours). Patients with coagulopathy and highly vascularized tumor were more vulnerable to spinal epidural hematoma. The postoperative outcome was related to the preoperative neurological deficit and the time interval to the decompression.

Difference in Occurrence of Heterotopic Ossification According to Prosthesis Type in the Cervical Artificial Disc Replacement

Study Design. Retrospective study of the difference of heterotopic ossification (HO) occurrence according to 3 different types of prosthesis. Objective. This study was designed to investigate the difference of HO occurrence according to different type of prosthesis. Summary of Background Data. HO is defined as formation of the bone outside the skeletal system. Reported HO occurrence rate in cervical artificial disc replacement (ADR) was unexpectedly high and varied. But the influencing factors of HO in cervical ADR have not been elucidated well. The prosthesis-related factors for making difference of HO occurrence were investigated in this study. Methods. A total of 170 patients undergoing cervical arthroplasty with the Bryan cervical disc prosthesis (Medtroic Sofamor Danek, Memphis, TN), Mobi-C disc prosthesis (LDR Medical, Troyes, France), and ProDisc-C (Synthes, Inc., West Chester, PA) were included. Cervical lateral radiographs obtained before and after surgery were used to identify HO. Occurrence rate, occurrence-free period, location, and grade of HOs were investigated according to the different prosthesis. Results. Each prosthesis group included patients as follows: Bryan disc, 81 patients; Mobi-C, 61 patients; and ProDisc-C, 28 patients. Overall HO rate was 40.6% (69 of 170 patients). Each HO occurrence rate by prosthesis was as follows: the Bryan disc group, 21.0%; Mobi-C group, 52.5%; and the ProDisc-C group, 71.4%. In the survival analysis, all patients showed 27.1 ± 3.7 months as the median survival. The Bryan disc group showed statistically longer survival (48.4 ± 7.4 months) than the other groups. Conclusion. Occurrence of HO is an inevitable postoperative complication after cervical ADR. The occurrence rate of HO was higher than our expectation. Moreover, definite differences in occurrence rate according to the prosthesis type were identified by this study.

The efficacy of microendoscopic discectomy in reducing iatrogenic muscle injury

OBJECT The objective of this study was to evaluate the invasiveness of microendoscopic discectomy (MED) in comparison with microscopic discectomy (MD) by measuring serum levels of creatine phosphokinase (CPK)-MM and lactate dehydrogenase (LDH)-5, and by comparing visual analog scale (VAS) scores of postoperative pain. METHODS This study included a group of 15 patients who underwent surgery using MED and 15 patients who underwent surgery using MD, both for single-level unilateral herniated nucleus pulposus. The CPK-MM and LDH-5 levels were measured at admission and after 1, 3, and 5 days postoperatively. Pain assessment was recorded using scores raging from 0 to 10 on a subjective VAS at admission and at 1, 3, and 5 days postoperatively. RESULTS The mean CPK-MM levels were lower for the MED group than for the MD group at both 3 (576.1 +/- 286.3 IU/L compared with 968.1 +/- 377.8 IU/L) and 5 days (348.1 +/- 231.0 IU/L compared with 721.7 +/- 463.2) postoperatively (p < 0.05). The mean VAS scores for postoperative back pain were lower in the MED group than in the MD group, both at 1 (3.3 +/- 2.3 compared with 5.8 +/- 1.5) and 5 days (1.9 +/- 1.1 compared with 3.6 +/- 1.1) postoperatively (p < 0.01). CONCLUSIONS The MED procedure is less invasive than MD, and causes less muscle damage and less back pain.

Hypoxia-preconditioned adipose tissue-derived mesenchymal stem cell increase the survival and gene expression of engineered neural stem cells in a spinal cord injury model.

Hypoxic preconditioning (HP) is a novel strategy to make stem cells resistant to the ischemic environment they encounter after transplantation into injured tissue; this strategy improves survival of both the transplanted cells and the host cells at the injury site. Using both in vitro and in vivo injury models, we confirmed that HP-treated adipose tissue-derived mesenchymal stem cells (HP-AT-MSCs) increased cell survival and enhanced the expression of marker genes in DsRed-engineered neural stem cells (NSCs-DsRed). Similar to untreated AT-MSCs, HP-AT-MSCs had normal morphology and were positive for the cell surface markers CD90, CD105, and CD29, but not CD31. In three in vitro ischemic-mimicking injury models, HP-AT-MSCs significantly increased both the viability of NSCs-DsRed and the expression of DsRed and clearly reduced the number of annexin-V-positive apoptotic NSCs-DsRed and the expression of the apoptotic factor Bax. Consistent with the in vitro assay, co-transplantation of NSCs-DsRed with HP-AT-MSCs significantly improved the survival of the NSCs-DsRed, resulting in an increased expression of the DsRed reporter gene at the transplantation site in a rat spinal cord injury (SCI) model. These findings suggest that the co-transplantation of HP-AT-MSCs with engineered NSCs can improve both the cell survival and the gene expression of the engineered NSCs, indicating that this novel strategy can be used to augment the therapeutic efficacy of combined stem cell and gene therapies for SCI.

Cotransplantation of mouse neural stem cells (mNSCs) with adipose tissue-derived mesenchymal stem cells improves mNSC survival in a rat spinal cord injury model.

The low survival rate of graft stem cells after transplantation into recipient tissue is a major obstacle for successful stem cell therapy. After transplantation into the site of spinal cord injury, the stem cells face not only hypoxia due to low oxygen conditions, but also a lack of nutrients caused by damaged tissues and poor vascular supply. To improve the survival of therapeutic stem cells after grafting into the injured spinal cord, we examined the effects of cotransplanting mouse neural stem cells (mNSCs) and adipose tissue-derived mesenchymal stem cells (AT-MSCs) on mNSC viability. The viability of mNSCs in coculture with AT-MSCs was significantly increased compared to mNSCs alone in an in vitro injury model using serum deprivation (SD), hydrogen peroxide (H2O2), and combined (SD + H2O2) injury mimicking the ischemic environment of the injured spinal cord. We demonstrated that AT-MSCs inhibited the apoptosis of mNSCs in SD, H2O2, and combined injury models. Consistent with these in vitro results, mNSCs transplanted into rat spinal cords with AT-MSCs showed better survival rates than mNSCs transplanted alone. These findings suggest that cotransplantation of mNSCs with AT-MSCs may be a more effective transplantation protocol to improve the survival of cells transplanted into the injured spinal cord.

Effective dose of peri-operative oral pregabalin as an adjunct to multimodal analgesic regimen in lumbar spinal fusion surgery.

Study Design. A prospective, randomized, controlled, and double-blind trial. Objective. To evaluate the effects of 2 different doses of perioperative pregabalin administration, twice on the day of surgery, on acute postoperative pain after spinal surgery. Summary of Background Data. Besides its well-established role on neuropathic pain, pregabalin seems to be a promising adjunct to multimodal analgesic regimen following surgery. No comprehensive data exist regarding the optimal dosage of pregabalin on reducing postoperative pain and opioid consumption in spinal surgery. Methods. Patients were randomly assigned to 1 of 3 groups. The placebo group (n = 28) received placebo capsules 1 hour before the anesthetic induction and 12 hours after surgery. The pregabalin groups received pregabalin 75 mg (P75 group, n = 28) or 150 mg (P150 group, n = 28), respectively at the same points. Assessed variables were total amount of administered fentanyl-based intravenous patient-controlled analgesia, pain intensity, and the frequency of rescue analgesic administered during the first 48 hours after surgery, subdivided into the following 4 periods: on arrival of patient to the postanesthesia care unit, 1 to 6 hours, 6 to 24 hours, and 24 to 48 hours. Results. The amount of patient-controlled analgesia volume infused until 24 hours (P = 0.025) and 48 hours (P = 0.028) after surgery was significantly less in the P150 group compared with the control group. The frequency of additional anodynes administered until 6 hours (P = 0.049) and 24 hours (P = 0.045) after surgery was significantly less in the P150 group compared with the control group. Conclusion. Perioperative administration of pregabalin 150 mg before and 12 hours after surgery, but not 75 mg, significantly reduced opioid consumption and the use of additional pain rescue for 48 hours after surgery without significant side effects in patients undergoing spinal fusion surgery.

Modified Techniques to Prevent Sagittal Imbalance After Cervical Arthroplasty

Study Design. Retrospective study of radiographic outcomes in patients undergoing single level cervical arthroplasty with the Bryan cervical disc (Medtronic Sofamor Danek, Memphis, TN). Objective. This study was designed to determine whether modification of disc insertion angle and insertion depth are effective in preventing segmental or whole cervical kyphosis after arthroplasty. Summary of Background Data. Preservation of segmental motion and aggravation of kyphosis are known challenges after arthroplasty. However, there are currently no proven preventative factors for kyphosis. Change in disc insertion angle was only reported effective for avoiding endplate kyphosis. Additionally, it was difficult to predict the effect of insertion angle on overall sagittal alignment. There have been no studies regarding the correlation between insertion depth and sagittal alignment. Methods. A total of 41 patients with single-level arthroplasty were evaluated. Radiologic assessment using neutral cervical radiographs at the long-term was performed. Linear regression analysis between insertion angle, insertion depth, postoperative sagittal alignment, functional spinal unit angle, and shell angle were performed. Results. Disc insertion angle and insertion depth demonstrated significant negative correlation with the postoperative shell angle. Lordotic insertion angle and an anteriorly located disc led to lordosis in the shell angle. Overall sagittal alignment showed a tendency to correlate with insertion angle. By the result of effect of insertion angle ranging from 3.5° to 7.5° on the sagittal alignment and shell angle, we can hypothesize paradoxical biomechanical stress on the other segments. Conclusion. Arthroplasty using the Bryan disc provided a favorable clinical and radiologic outcome thus far; however, we should not underestimate emergent adverse outcomes. To prevent postoperative sagittal imbalance after cervical arthroplasty, intentional modification in disc insertion angle and depth would be helpful. Unexpected compensatory biomechanical loads should be elucidated in future studies.

The predisposing factors for the heterotopic ossification after cervical artificial disc replacement

BACKGROUND CONTEXT Heterotopic ossification (HO) is defined as a formation of bone outside the skeletal system. The reported HO occurrence rate in cervical artificial disc replacement (ADR) is unexpectedly high and is known to vary. However, the predisposing factors for HO in cervical ADR have not yet been elucidated. PURPOSE Investigation of the predisposing factors of HO in cervical arthroplasty and the relationship between degeneration of the cervical spine and HO occurrence. STUDY DESIGN Retrospective study to discover predisposing factors of HO in cervical arthroplasty. PATIENT SAMPLE A total of 170 patients who underwent cervical ADR were enrolled including full follow-up clinical and radiologic data. OUTCOME MEASURES Radiologic outcomes were assessed by identification of HOs according to McAfees classifications. METHODS This study enrolled a total of 170 patients who underwent cervical ADR. Pre-existing degenerative change included anterior or posterior osteophytes, ossification of the anterior longitudinal ligament, posterior longitudinal ligament, or ligamentum nuchae. The relationships between basic patient data, pre-existing degenerative change, and HO were investigated using linear logistic regression analysis. RESULTS Among all 170 patients, HO was found in 69 patients (40.6%). Among the postulated predisposing factors, only male gender and artificial disc device type were shown to be statistically significant. Unexpectedly, preoperative degenerative changes in the cervical spine exerted no significant influence on the occurrence of HOs. The odds ratio of male gender compared with female gender was 2.117. With regard to device type, the odds ratios of Mobi-C (LDR medical, Troyes, France) and ProDisc-C (Synthes, Inc., West Chester, PA, USA) were 5.262 and 7.449, respectively, compared with the Bryan disc. CONCLUSIONS Definite differences in occurrence rate according to the gender of patients and the prosthesis type were identified in this study. Moreover, factors indefinably expected to influence HO in the past were not shown to be risk factors thereof, the results of which may be meaningful to future studies.