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Clinical Implications and Risk Factors of Heterotopic Ossification at 7 Years after Cervical Total Disc Replacement
NASS 32nd Annual Meeting Proceedings / The Spine Journal 17 (2017) S89–S110 STUDY DESIGN/SETTING: Post-hoc analysis from a prospective, randomized, multicenter, US FDA clinical trial of TDR vs ACDF. PATIENT SAMPLE: Inclusion criteria required a diagnosis of degenerative disc disease at two contiguous levels between C3 and C7 with radiculopathy or myeloradiculopathy. A total of 330 two-level patients were randomized and treated, resulting in 225 patients receiving a TDR with Mobi-C (Zimmer Biomet, Austin, TX) and 105 patients receiving an ACDF with allograft and an anterior plate. OUTCOME MEASURES: NDI, SF-12 MCS/PCS and VAS neck pain were recorded at preoperative and at 6, 12, 24, 36, 48 and 60 months. The 10 NDI items measured symptoms and disability related to pain intensity, personal care, lifting, reading, headaches, concentration, work, sleeping, driving and recreation. Item responses were converted to a 6-point scale, with “0” referring to no disability and “5” referring to severe disability. METHODS: Mixed-effects analysis of variance (ANOVA) was applied to the improvement in NDI item score to analyze the effect of treatment option (TDR vs ACDF) on changes in individual NDI item scores. We also regressed improvement in VAS neck pain, SF-12 PCS and SF-12 MCS onto improvement in NDI item scores. Type 3 tests of fixed effects were used to determine significant (p<.05) effects. RESULTS: There was significant variability in the degree of improvement between NDI items. Improvements in recreation, work and sleeping, were highly correlated while other items (eg, headaches) were uncorrelated. There was a significant time-averaged treatment effect, in favor of TDR, for sleeping, driving, work, headaches, reading, lifting, personal care, recreation and pain intensity. The headache item demonstrated the largest improvement in the TDR cohort, followed by lifting and sleeping. Recreation item scores worsened in the ACDF group between two-year and five-year follow-up. Regression analysis revealed that improvements in work, recreation, pain intensity, lifting and reading were all significantly associated with improvements in SF-12 PCS. The other items were not significantly associated with SF-12 PCS. Improvement in personal care, sleeping, pain intensity, concentration and work were significantly associated with SF-12 MCS. VAS neck pain was most associated with the pain intensity item. CONCLUSIONS: Treatment with TDR resulted in significantly greater improvement vs ACDF in nine of 10 NDI items, and these differences were maintained through five years. There are significant limitations in the usage of aggregate NDI improvement as a measure of clinical outcome since there are high correlations between some items. Some NDI items appear to be unrelated to health-related quality of life in regression analysis. We believe that future studies should report individual NDI item scores as well as aggregate scores to help elucidate whether the NDI is a reasonable outcome measure of cervical spine surgery. FDA DEVICE/DRUG STATUS: Mobi-C Cervical Disc (Approved for this indication).
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PATIENT SAMPLE: The original study cohort consisted of 599 patients treated with one- or two-level TDR or ACDF. The inclusion criteria included a diagnosis of symptomatic cervical degenerative disc disease at one or two contiguous levels and no history of cervical spine surgery. OUTCOME MEASURES: Measured outcomes included adjacent segment degeneration (ASD), subsequent surgery, Neck Disability Index (NDI), VAS neck and arm pain, SF-12 MCS/PCS, range of motion and sagittal alignment. METHODS: TDR patients were treated with the Mobi-C© artificial disc (Zimmer Biomet, Austin, TX). ACDF with allograft and anterior plate was the control treatment. Outcomes were collected preoperatively and postoperatively up to 84 months. Independent radiologists conducted all radiographic evaluations. HO was classified using the system adapted from McAfee and Mehren. Outcomes after Grade 4 HO were compared to mobile TDR (TDRm) and ACDF patients matched by gender and operated level (C4–C7). RESULTS: At 7 years, Grade 4 HO occurred in 46 of 413 TDR patients (11%). Mean time to Grade 4 HO was 39.7 months (11–87 months). Mean follow-up after first occurrence of Grade 4 HO was 36.4 months (range 0–75 months). The TDRf patients were compared to 152 ACDF patients and 300 patients with mobile TDR (TDRm). At last follow-up, radiographic ASD (KL grade 3/4) was significantly higher in TDRf compared to TDRm (29.6% vs 17.4%; p=.03), but TDRf patients had less ASD than ACDF patients (29.6% vs 38.6%; p=.08). Survival curves showed similar freedom from Grade 4 ASD for TDRf compared to ACDF (87.3% vs 92.6%; p=.20) at 72 months. Subsequent surgeries were lower for TDRf vs ACDF at the index level (0% vs 11.8%; p=.007), adjacent levels (4.4% vs 9.2%; p=.16), and for all subsequent surgeries (4.4% vs 15.8%; p=.025). For index level surgeries, the majority of procedures in ACDF patients were due to pseudarthrosis, a major cause of reoperation after ACDF that would not occur in TDRf patients. Survival curves illustrated higher freedom from any subsequent surgery for TDRf compared to ACDF at 72 months (89.2% vs 83.3%; p=.23). At last followup, mean NDI was 17.7±19.3 for TDRm, 22.1±21.0 for TDRf, and 22.5±20.6 for ACDF. Mean VAS neck pain was 18.7±26.9 for TDRm, 23.2±28.2 for TDRf, and 25.8±28.9 for ACDF. Segmental ROM in TDRf patients was similar to ACDF, and TDRf patients maintained sagittal alignment after fusion. CONCLUSIONS: Patients with motion-restricting HO had similar or better patient-reported outcomes, and delayed progression of ASD compared to ACDF. Subsequent surgery rates after HO-induced fusion were significantly lower than ACDF. Up to 6 years after occurrence of Grade 4 HO, there was no evidence that TDRf patients have worse outcomes than primary ACDF. In spite of the similarities to ACDF, TDRf patients benefited from over 3 years of improved quality of life gained on average from TDR over ACDF. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs. https://doi.org/10.1016/j.spinee.2017.07.156
https://doi.org/10.1016/j.spinee.2017.07.155
130. Outcomes after Motion-Restricting Heterotopic Ossification in Patients with Cervical Total Disc Replacement: How Do They Compare to ACDF? Robert J. Jackson, MD, FACS1, Hyun W. Bae, MD2, Darin E. Johnson, PA-C1, Bill Dolman3; 1Laguna Hills, CA, USA; 2Spine Institute St. John’s Health Center, Los Angeles, CA, USA; 3Austin, TX, USA BACKGROUND CONTEXT: Heterotopic ossification (HO) can occur after treatment with cervical total disc replacement (TDR). In severe cases, HO can limit range of motion, and result in fusion of the segment. The longterm effects of HO resulting in unintended fusion have not been analyzed. PURPOSE: To compare the safety and effectiveness of TDR after onset of motion-restricting HO (Grade 4; TDRf) to ACDF for the treatment of cervical degenerative disc disease. STUDY DESIGN/SETTING: Post hoc analysis of TDR patients with Grade 4 HO compared to a matched group of patients with ACDF and mobile TDR. All patients were from a prospective, randomized, multicenter clinical trial.
131. Clinical Implications and Risk Factors of Heterotopic Ossification at 7 Years after Cervical Total Disc Replacement Pierce D. Nunley, MD, David A. Cavanaugh, MD, Eubulus J. Kerr III, MD, Andrew Utter, MD, Peter Campbell, MD, Kelly Frank, MS, Marcus Stone, PhD; Spine Institute of Louisiana, Shreveport, LA, USA BACKGROUND CONTEXT: Heterotopic ossification (HO) is a known risk following cervical total disc replacement (CTDR) surgery, but potential risk factors and impacts on outcomes remain unknown. Reported HO rates vary, and few studies are specifically designed to report HO. The effects on outcomes, and the risk factors for development of HO have been hypothesized and reported in literature, but the studies included small populations, retrospective analyses, and the use of univariate statistics. PURPOSE: The study was designed to report HO prevalence, progression, clinical implications, and risk factors following CTDR surgery. STUDY DESIGN/SETTING: Post hoc, multiple phase analysis of radiographic, clinical and demographic data for cervical total disc replacement CTDR as it relates to HO.
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NASS 32nd Annual Meeting Proceedings / The Spine Journal 17 (2017) S89–S110
PATIENT SAMPLE: Patients were treated with CTDR as part of the MobiC, FDA, IDE clinical trial and included 164 treated at one level and 225 at two levels. OUTCOME MEASURES: Radiographs and clinical outcomes were collected annually through year 5 and at year 7. Clinical outcomes included neck disability index (NDI), VAS neck/arm pain, and Short Form (SF)-12 Physical Component Score (PCS)/Mental Component Score (MCS). Demographics and baseline clinical scores included age, gender, body mass index (BMI), segmental range of motion (ROM) in flexion/extension, Visual Analog Scale (VAS) neck pain and disc space height. METHODS: HO was radiographically graded with the McAfee and Mehren system, with grades 3 and 4 designated as clinically relevant. Analysis using mixed effects analysis of variance (ANOVA) was performed to correlate HO grades to clinical outcomes. Potential risk factors for development of HO, using demographics and baseline clinical measures, were identified by mixed effects logistic regression and a mixed effects Cox proportional hazards model. RESULTS: At 7 years, one-level clinically relevant HO grades were 17.6% grade 3 and 11.1% grade 4. Two-level clinically relevant HO grades, evaluated using the highest patient grade, were 26.6% grade 3 and 10.8% grade 4. When analyzed at each time point NDI was significant at 48–84 months and VAS neck at 60 months, yet these were not clinically significant. For predictors, using the mixed effects logistic regression, odds ratios indicated time, male gender and preoperative VAS neck pain are related to HO development,. The Cox proportional hazards ratios indicated male gender, obesity, endplate coverage, levels treated and preoperative VAS neck pain were significant predictors of HO development. CONCLUSIONS: At 7-years, one-level clinically relevant HO grades were 17.6% grade 3 and 11.1% grade 4. Two-level clinically relevant HO grades, evaluated using the highest patient grade, were 26.6% grade 3 and 10.8% grade 4. When analyzed at each time point, NDI was significant at 48–84 months and VAS neck at 60 months, yet these were not clinically significant. For predictors, using the mixed effects logistic regression, odds ratios indicated time, male gender and preoperative VAS neck pain are related to HO development. The Cox proportional hazards ratios indicated male gender, obesity, endplate coverage, levels treated and preoperative VAS neck pain were significant predictors of HO development. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs. https://doi.org/10.1016/j.spinee.2017.07.157
Thursday, October 26, 2017 3:40 PM–5:10 PM Section on Biologics and Basic Research Abstract Presentations 132. Pentosan Polysulfate Primed Mesenchymal Progenitor Cells Mediate Disc Repair following Microdiscectomy in an Ovine Model Christopher Daly, MBBS, M.Phil1,2,3, Peter Ghosh, D.Sc, PhD, FRSC1,4, Tanya Badal, MSc6, Ronald G. Shimmon, PhD6, David A. Oehme, MBBS, PhD, FRACS5, Idrees Sher, MBBS, BSc2,3, Ronil V. Chandra, MBBS, FRANZCR3,7, Angela Vais8, Camilla A. Cohen8, Tony Goldschlager, MBBS, PhD, FRACS1,2; 1The Ritchie Centre, Hudson Institute of Medical Research, Monash University, Clayton, Victoria, Australia; 2Department of Neurosurgery, Monash Medical Centre, Clayton, Victoria, Australia; 3Department of Surgery, Monash University, Clayton, Victoria, Australia; 4Proteobioactives, Pty Ltd, Brookvale, New South Wales, Australia; 5Department of Neurosurgery, St. Vincent’s Hospital, Fitzroy, Victoria, Australia; 6Technical Services Research, University of Technology, Sydney, Australia; 7Department of Imaging, Monash Medical Centre, Clayton, Victoria, Australia; 8Monash Histology Platform, Monash University, Clayton, Victoria, Australia
BACKGROUND CONTEXT: Lumbar microdiscectomy targets neural decompression associated with lumbar disc herniation. However, it fails to halt the underlying process of disc degeneration. As a consequence, 10–20% of patients re-present with debilitating back pain and approximately 15% undergo further surgical intervention. In-vitro studies have demonstrated that preincubation of mesenchymal progenitor cells (MPCs) with the sulphated polysaccharide, pentosan polysulfate (PPS), for 24 hours, enhances their chondrogenic differentiation and viability. PURPOSE: The present study investigated the potential of PPS primed MPCs (pMPCs), embedded in a gelatin sponge scaffold and inserted into the lesion produced by microdiscectomy, to facilitate disc repair using an ovine model. STUDY DESIGN/SETTING: N/A. PATIENT SAMPLE: N/A. OUTCOME MEASURES: N/A. METHODS: Eighteen adult ewes underwent preoperative 3T MRI. Microdiscectomy was performed via a lateral retroperitoneal surgical approach at two lumbar disc levels. Adjacent nonoperated lumbar discs served as normal controls. The microdiscectomy procedure consisted of a standardized 3 x 5 mm annulotomy with removal of approximately 200 mg of annulus fibrosus (AF) plus some nucleous pulposus (NP) tissues. Sheep were randomized into three groups (n=6) following microdiscectomy. Group 1, received no further treatment (injured control group); Group 2 were implanted with nonprimed MPC (500,000 cells)+scaffold; Group 3 received the pMPC (500,000 cells)+scaffold. Necropsies were performed at six months and lumbar spines were scanned using 3T and 9.4T MRI and radiographic imaging. Spinal columns were dissected, individual discs sectioned and NP and AF regions scored using gross morphological and histological assessments. Following subdivision of the discs into six regional segments, NP and AF tissues were analyzed biochemically for their proteoglycans (PGs) (as S-GAGs), collagen and DNA content. RESULTS: The MPC and pMPC groups (Groups 2 & 3) demonstrated significantly less reduction in disc height relative to the injury group (Group 1) (p<.05). No significant difference among groups was observed in Pfirrmann 3T degeneration scores. Gross morphological scoring revealed significantly reduced degeneration scores in Group 3 disc segments overall compared to Group 1 for the NP and AF. The PG content of the NP contralateral to the injury for the pMPC group (Group 3) was significantly higher than for Group 1 (p<.01) and not statistically different to the normal control disc values. The PG content of Group 3 discs at the site of injury were greater than Group 1 discs (p<.02). The PG content of the contralateral AF of Group 3 was not significantly different to normal controls discs and greater than Groups 2 discs (p<.04). DNA content for Group 3 discs was significantly lower than Group 1 discs for the AF injury site, adjacent AF regions and the nucleus pulposus ipsilateral and contralateral to the lesion. Histological analysis revealed evidence of increased organization and decreased degeneration in Group 3 discs relative to Group 1 discs. Group 2 intervertebral discs demonstrated increased vascular infiltration relative to Group 1 and 3 discs. CONCLUSIONS: Local administration of pMPCs (Group 3), embedded in the gelatin scaffold, post microdiscectomy reduced disc degeneration, improved disc matrix organization and disc height and NP proteoglycan content relative to microdiscectomy alone (Group 1). The reduced vascular infiltration evident in Group 3 discs relative to Group 2 discs correlated with their lower morphological scores and DNA levels which was consistent with decreased inflammatory cell infiltration and angiogenesis. These findings coupled with the significantly improved morphological, histological and biochemical data, relative to the Group 1 discs suggest a potential therapeutic application of pMPCs in limiting the extent of spontaneous disc degeneration, promoting repair and the subsequent recurrence of low back pain and radiculopathy in patients following lumbar microdiscectomy. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs. https://doi.org/10.1016/j.spinee.2017.07.159
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PATIENT SAMPLE: The original study cohort consisted of 599 patients treated with one- or two-level TDR or ACDF. The inclusion criteria included a diagnosis of symptomatic cervical degenerative disc disease at one or two contiguous levels and no history of cervical spine surgery. OUTCOME MEASURES: Measured outcomes included adjacent segment degeneration (ASD), subsequent surgery, Neck Disability Index (NDI), VAS neck and arm pain, SF-12 MCS/PCS, range of motion and sagittal alignment. METHODS: TDR patients were treated with the Mobi-C© artificial disc (Zimmer Biomet, Austin, TX). ACDF with allograft and anterior plate was the control treatment. Outcomes were collected preoperatively and postoperatively up to 84 months. Independent radiologists conducted all radiographic evaluations. HO was classified using the system adapted from McAfee and Mehren. Outcomes after Grade 4 HO were compared to mobile TDR (TDRm) and ACDF patients matched by gender and operated level (C4–C7). RESULTS: At 7 years, Grade 4 HO occurred in 46 of 413 TDR patients (11%). Mean time to Grade 4 HO was 39.7 months (11–87 months). Mean follow-up after first occurrence of Grade 4 HO was 36.4 months (range 0–75 months). The TDRf patients were compared to 152 ACDF patients and 300 patients with mobile TDR (TDRm). At last follow-up, radiographic ASD (KL grade 3/4) was significantly higher in TDRf compared to TDRm (29.6% vs 17.4%; p=.03), but TDRf patients had less ASD than ACDF patients (29.6% vs 38.6%; p=.08). Survival curves showed similar freedom from Grade 4 ASD for TDRf compared to ACDF (87.3% vs 92.6%; p=.20) at 72 months. Subsequent surgeries were lower for TDRf vs ACDF at the index level (0% vs 11.8%; p=.007), adjacent levels (4.4% vs 9.2%; p=.16), and for all subsequent surgeries (4.4% vs 15.8%; p=.025). For index level surgeries, the majority of procedures in ACDF patients were due to pseudarthrosis, a major cause of reoperation after ACDF that would not occur in TDRf patients. Survival curves illustrated higher freedom from any subsequent surgery for TDRf compared to ACDF at 72 months (89.2% vs 83.3%; p=.23). At last followup, mean NDI was 17.7±19.3 for TDRm, 22.1±21.0 for TDRf, and 22.5±20.6 for ACDF. Mean VAS neck pain was 18.7±26.9 for TDRm, 23.2±28.2 for TDRf, and 25.8±28.9 for ACDF. Segmental ROM in TDRf patients was similar to ACDF, and TDRf patients maintained sagittal alignment after fusion. CONCLUSIONS: Patients with motion-restricting HO had similar or better patient-reported outcomes, and delayed progression of ASD compared to ACDF. Subsequent surgery rates after HO-induced fusion were significantly lower than ACDF. Up to 6 years after occurrence of Grade 4 HO, there was no evidence that TDRf patients have worse outcomes than primary ACDF. In spite of the similarities to ACDF, TDRf patients benefited from over 3 years of improved quality of life gained on average from TDR over ACDF. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs. https://doi.org/10.1016/j.spinee.2017.07.156
https://doi.org/10.1016/j.spinee.2017.07.155
130. Outcomes after Motion-Restricting Heterotopic Ossification in Patients with Cervical Total Disc Replacement: How Do They Compare to ACDF? Robert J. Jackson, MD, FACS1, Hyun W. Bae, MD2, Darin E. Johnson, PA-C1, Bill Dolman3; 1Laguna Hills, CA, USA; 2Spine Institute St. John’s Health Center, Los Angeles, CA, USA; 3Austin, TX, USA BACKGROUND CONTEXT: Heterotopic ossification (HO) can occur after treatment with cervical total disc replacement (TDR). In severe cases, HO can limit range of motion, and result in fusion of the segment. The longterm effects of HO resulting in unintended fusion have not been analyzed. PURPOSE: To compare the safety and effectiveness of TDR after onset of motion-restricting HO (Grade 4; TDRf) to ACDF for the treatment of cervical degenerative disc disease. STUDY DESIGN/SETTING: Post hoc analysis of TDR patients with Grade 4 HO compared to a matched group of patients with ACDF and mobile TDR. All patients were from a prospective, randomized, multicenter clinical trial.
131. Clinical Implications and Risk Factors of Heterotopic Ossification at 7 Years after Cervical Total Disc Replacement Pierce D. Nunley, MD, David A. Cavanaugh, MD, Eubulus J. Kerr III, MD, Andrew Utter, MD, Peter Campbell, MD, Kelly Frank, MS, Marcus Stone, PhD; Spine Institute of Louisiana, Shreveport, LA, USA BACKGROUND CONTEXT: Heterotopic ossification (HO) is a known risk following cervical total disc replacement (CTDR) surgery, but potential risk factors and impacts on outcomes remain unknown. Reported HO rates vary, and few studies are specifically designed to report HO. The effects on outcomes, and the risk factors for development of HO have been hypothesized and reported in literature, but the studies included small populations, retrospective analyses, and the use of univariate statistics. PURPOSE: The study was designed to report HO prevalence, progression, clinical implications, and risk factors following CTDR surgery. STUDY DESIGN/SETTING: Post hoc, multiple phase analysis of radiographic, clinical and demographic data for cervical total disc replacement CTDR as it relates to HO.
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NASS 32nd Annual Meeting Proceedings / The Spine Journal 17 (2017) S89–S110
PATIENT SAMPLE: Patients were treated with CTDR as part of the MobiC, FDA, IDE clinical trial and included 164 treated at one level and 225 at two levels. OUTCOME MEASURES: Radiographs and clinical outcomes were collected annually through year 5 and at year 7. Clinical outcomes included neck disability index (NDI), VAS neck/arm pain, and Short Form (SF)-12 Physical Component Score (PCS)/Mental Component Score (MCS). Demographics and baseline clinical scores included age, gender, body mass index (BMI), segmental range of motion (ROM) in flexion/extension, Visual Analog Scale (VAS) neck pain and disc space height. METHODS: HO was radiographically graded with the McAfee and Mehren system, with grades 3 and 4 designated as clinically relevant. Analysis using mixed effects analysis of variance (ANOVA) was performed to correlate HO grades to clinical outcomes. Potential risk factors for development of HO, using demographics and baseline clinical measures, were identified by mixed effects logistic regression and a mixed effects Cox proportional hazards model. RESULTS: At 7 years, one-level clinically relevant HO grades were 17.6% grade 3 and 11.1% grade 4. Two-level clinically relevant HO grades, evaluated using the highest patient grade, were 26.6% grade 3 and 10.8% grade 4. When analyzed at each time point NDI was significant at 48–84 months and VAS neck at 60 months, yet these were not clinically significant. For predictors, using the mixed effects logistic regression, odds ratios indicated time, male gender and preoperative VAS neck pain are related to HO development,. The Cox proportional hazards ratios indicated male gender, obesity, endplate coverage, levels treated and preoperative VAS neck pain were significant predictors of HO development. CONCLUSIONS: At 7-years, one-level clinically relevant HO grades were 17.6% grade 3 and 11.1% grade 4. Two-level clinically relevant HO grades, evaluated using the highest patient grade, were 26.6% grade 3 and 10.8% grade 4. When analyzed at each time point, NDI was significant at 48–84 months and VAS neck at 60 months, yet these were not clinically significant. For predictors, using the mixed effects logistic regression, odds ratios indicated time, male gender and preoperative VAS neck pain are related to HO development. The Cox proportional hazards ratios indicated male gender, obesity, endplate coverage, levels treated and preoperative VAS neck pain were significant predictors of HO development. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs. https://doi.org/10.1016/j.spinee.2017.07.157
Thursday, October 26, 2017 3:40 PM–5:10 PM Section on Biologics and Basic Research Abstract Presentations 132. Pentosan Polysulfate Primed Mesenchymal Progenitor Cells Mediate Disc Repair following Microdiscectomy in an Ovine Model Christopher Daly, MBBS, M.Phil1,2,3, Peter Ghosh, D.Sc, PhD, FRSC1,4, Tanya Badal, MSc6, Ronald G. Shimmon, PhD6, David A. Oehme, MBBS, PhD, FRACS5, Idrees Sher, MBBS, BSc2,3, Ronil V. Chandra, MBBS, FRANZCR3,7, Angela Vais8, Camilla A. Cohen8, Tony Goldschlager, MBBS, PhD, FRACS1,2; 1The Ritchie Centre, Hudson Institute of Medical Research, Monash University, Clayton, Victoria, Australia; 2Department of Neurosurgery, Monash Medical Centre, Clayton, Victoria, Australia; 3Department of Surgery, Monash University, Clayton, Victoria, Australia; 4Proteobioactives, Pty Ltd, Brookvale, New South Wales, Australia; 5Department of Neurosurgery, St. Vincent’s Hospital, Fitzroy, Victoria, Australia; 6Technical Services Research, University of Technology, Sydney, Australia; 7Department of Imaging, Monash Medical Centre, Clayton, Victoria, Australia; 8Monash Histology Platform, Monash University, Clayton, Victoria, Australia
BACKGROUND CONTEXT: Lumbar microdiscectomy targets neural decompression associated with lumbar disc herniation. However, it fails to halt the underlying process of disc degeneration. As a consequence, 10–20% of patients re-present with debilitating back pain and approximately 15% undergo further surgical intervention. In-vitro studies have demonstrated that preincubation of mesenchymal progenitor cells (MPCs) with the sulphated polysaccharide, pentosan polysulfate (PPS), for 24 hours, enhances their chondrogenic differentiation and viability. PURPOSE: The present study investigated the potential of PPS primed MPCs (pMPCs), embedded in a gelatin sponge scaffold and inserted into the lesion produced by microdiscectomy, to facilitate disc repair using an ovine model. STUDY DESIGN/SETTING: N/A. PATIENT SAMPLE: N/A. OUTCOME MEASURES: N/A. METHODS: Eighteen adult ewes underwent preoperative 3T MRI. Microdiscectomy was performed via a lateral retroperitoneal surgical approach at two lumbar disc levels. Adjacent nonoperated lumbar discs served as normal controls. The microdiscectomy procedure consisted of a standardized 3 x 5 mm annulotomy with removal of approximately 200 mg of annulus fibrosus (AF) plus some nucleous pulposus (NP) tissues. Sheep were randomized into three groups (n=6) following microdiscectomy. Group 1, received no further treatment (injured control group); Group 2 were implanted with nonprimed MPC (500,000 cells)+scaffold; Group 3 received the pMPC (500,000 cells)+scaffold. Necropsies were performed at six months and lumbar spines were scanned using 3T and 9.4T MRI and radiographic imaging. Spinal columns were dissected, individual discs sectioned and NP and AF regions scored using gross morphological and histological assessments. Following subdivision of the discs into six regional segments, NP and AF tissues were analyzed biochemically for their proteoglycans (PGs) (as S-GAGs), collagen and DNA content. RESULTS: The MPC and pMPC groups (Groups 2 & 3) demonstrated significantly less reduction in disc height relative to the injury group (Group 1) (p<.05). No significant difference among groups was observed in Pfirrmann 3T degeneration scores. Gross morphological scoring revealed significantly reduced degeneration scores in Group 3 disc segments overall compared to Group 1 for the NP and AF. The PG content of the NP contralateral to the injury for the pMPC group (Group 3) was significantly higher than for Group 1 (p<.01) and not statistically different to the normal control disc values. The PG content of Group 3 discs at the site of injury were greater than Group 1 discs (p<.02). The PG content of the contralateral AF of Group 3 was not significantly different to normal controls discs and greater than Groups 2 discs (p<.04). DNA content for Group 3 discs was significantly lower than Group 1 discs for the AF injury site, adjacent AF regions and the nucleus pulposus ipsilateral and contralateral to the lesion. Histological analysis revealed evidence of increased organization and decreased degeneration in Group 3 discs relative to Group 1 discs. Group 2 intervertebral discs demonstrated increased vascular infiltration relative to Group 1 and 3 discs. CONCLUSIONS: Local administration of pMPCs (Group 3), embedded in the gelatin scaffold, post microdiscectomy reduced disc degeneration, improved disc matrix organization and disc height and NP proteoglycan content relative to microdiscectomy alone (Group 1). The reduced vascular infiltration evident in Group 3 discs relative to Group 2 discs correlated with their lower morphological scores and DNA levels which was consistent with decreased inflammatory cell infiltration and angiogenesis. These findings coupled with the significantly improved morphological, histological and biochemical data, relative to the Group 1 discs suggest a potential therapeutic application of pMPCs in limiting the extent of spontaneous disc degeneration, promoting repair and the subsequent recurrence of low back pain and radiculopathy in patients following lumbar microdiscectomy. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs. https://doi.org/10.1016/j.spinee.2017.07.159