Study Design. Preclinical animal study. Objective. Determine the in vivo effects of platelet-derived growth factor BB (PDGF-BB) delivered in a thiol-modified hyaluronic acid (TMHA) hydrogel on intervertebral disk (IVD) degeneration. Summary of Background Data. IVD degeneration is a worldwide health concern and remains without an effective treatment. Several in vitro studies have demonstrated the potential of PDGF-BB, a primary component of platelet-rich plasma, as a therapy for IVD degeneration. Our hypotheses were that treatment of injured IVDs with PDGF would inhibit degeneration and that administration of PDGF in a TMHA hydrogel would improve its efficacy. Methods. IVD degeneration was induced using the rabbit annular puncture model. Four weeks after injury, IVDs were treated with either PDGF-BB or PDGF-BB delivered within a TMHA hydrogel. The efficacy of treatment was determined using x-ray, MRI, histology, and biomechanical testing. Results. At 4 weeks after treatment, cell apoptosis and deposition of matrix containing type III collagen a1 (Col3a1) was demonstrated in both the nucleus pulposus and annulus fibrosus, while this was inhibited by PDGF. At 8 weeks after treatment, disc area and MRI indices of injured IVDs treated with PDGF were significantly higher (P < 0.05) than those treated with the TMHA alone. Similarly, degenerative scores for saline- and TMHA-treated IVDs demonstrated significantly more degeneration (P < 0.05) than PDGF-treated IVDs at 8 weeks. Biomechanical assessments found fewer indicators of degeneration in PDGF-TMHA-treated IVDs at both 4 and 8 weeks post-treatment, compared to saline-, TMHA-, and PDGF-only-treated IVDs. Both PDGF- and PDGF-TMHA-treated IVDs also demonstrated a significant increase (P < 0.05) in compressive strength to failure, compared with controls at 8 weeks post-treatment. Conclusion. The results of this study suggest that PDGF-BB significantly decreases disc degeneration and when delivered in a TMHA gel scaffold, helps prevent both apoptosis and Col3 matrix production, while maintaining disc structure and biomechanical function. Level of Evidence: NA

Millions of people worldwide suffer from low back pain and disability associated with intervertebral disc (IVD) degeneration. IVD degeneration is highly correlated with aging, as the nucleus pulposus (NP) dehydrates and the annulus fibrosus (AF) fissures form, which often results in intervertebral disc herniation or disc space collapse and related clinical symptoms. Currently available options for treating intervertebral disc degeneration are symptoms control with therapy modalities, and/or medication, and/or surgical resection of the IVD with or without spinal fusion. As such, there is an urgent clinical demand for more effective disease-modifying treatments for this ubiquitous disorder, rather than the current paradigms focused only on symptom control. Hydrogels are unique biomaterials that have a variety of distinctive qualities, including (but not limited to) biocompatibility, highly adjustable mechanical characteristics, and most importantly, the capacity to absorb and retain water in a manner like that of native human nucleus pulposus tissue. In recent years, various hydrogels have been investigated in vitro and in vivo for the repair of intervertebral discs, some of which are ready for clinical testing. In this review, we summarize the latest findings and developments in the application of hydrogel technology for the repair and regeneration of intervertebral discs.

Degeneration of the intervertebral disc (IVD) results in deterioration of the spinal motion segment and can lead to debilitating back pain. Given the established mitotic and anti-apoptotic effects of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) in a variety of cell types we postulated that rhPDGF-BB might delay disc cell degeneration through inhibition of apoptosis. To address this hypothesis, we treated human IVD cells isolated from five independent patients with rhPDGF-BB in monolayer and 3D pellet cultures. The anti-apoptotic potential, cell proliferative capacity, morphology/pellet differentiation, and gene expression of PDGF-treated IVD cells were evaluated via flow cytometry/immunohistochemistry, MTT assays, histology, and quantitative RT-PCR, respectively. We found that rhPDGF-BB treatment significantly inhibited cell apoptosis, increased cell proliferation and matrix production, and maintained mRNA expression of critical extracellular matrix genes. This study suggests two possible mechanisms for the anti-degenerative effects of rhPDGF-BB on human IVD cells. First, PDGF treatment strongly inhibited IVD cell apoptosis in 3D cultures. Second, rhPDGF-BB acts as an anabolic agent, promoting maintenance of IVD cell phenotype in 3D culture, based on the molecular and protein expression analysis. We speculate that rhPDGF-BB may be used as a biologic treatment to target early degenerative IVD disease in the future. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1181–1188, 2014.

Study Design: Retrospective review of prospective data. Objective: The objective of this study was to describe the clinical, radiographic, and complication-related outcomes through ≥1-year of 27 patients who underwent lateral lumbar interbody fusion (LLIF) with posterior instrumentation to treat ≥3 contiguous levels of degenerative lumbar scoliosis. Summary of Background Data: Multilevel disease has traditionally been treated with open posterior fusion. Literature on multilevel LLIF is limited. We present our experience with utilizing LLIF to treat multilevel degenerative scoliosis. Methods: Clinical outcomes were evaluated using VAS, SF-12, and ODI. Radiographic outcomes included pelvic tilt, pelvic incidence, lumbar lordosis, pelvic incidence-lumbar lordosis mismatch, Cobb angle, and cage subsidence. Perioperative and long-term complications through the ≥1-year final-postoperative visit were reviewed; transient neurological disturbances were assessed independently. Demographic, comorbidity, operative, and recovery variables, including opioid use, were explored for association with primary outcomes. Results: Mean time to final-postoperative visit was 22.5 months; levels treated with LLIF per patient, 3.7; age, 66 years; and lateral operative time, 203 minutes. EBL was ≤100 mL in 74% of cases. Clinical outcomes remained significantly improved at ≥1-year. Cobb angle was corrected from 21.1 to 7.9 degrees (P<0.001), lordosis from 47.3 to 52.6 degrees (P<0.001), and mismatch from 11.4 to 6.4 degrees (P=0.003). High-grade subsidence occurred in 3 patients. Subsidence did not significantly impact primary outcomes. In total, 11.1% returned to the operating room for complication-related intervention over nearly 2-years; 37% experienced complications. Experiencing a complication was associated with having an open-posterior portion (P=0.048), but not with number of LLIF levels treated, or with clinical or radiographic outcomes. No patients experienced protracted neurological deficits; psoas weakness was associated with increased lateral operative time (P=0.049) and decreased surgeon experience (P=0.028). Conclusions: Patients who underwent multilevel LLIF with adjunctive posterior surgery had significant clinical and radiographic improvements. Complication rates were similar compared to literature on single-level LLIF. LLIF is a viable treatment for multilevel degenerative scoliosis.

Background The prone transpsoas (PTP) approach for lateral lumbar interbody fusion (LLIF) is a relatively novel technique. Currently, little is known about its associated complications and early patient-reported outcomes. The aim of this study was to investigate the effect of LLIF performed via the PTP approach on sagittal radiographic parameters, patient-reported outcome measures (PROMs), and rates of complications. Methods A retrospective review was performed of 82 consecutive patients who underwent LLIF via a PTP technique. Lumbar lordosis (LL), segmental lordosis (SL), anterior disc height (ADH), and posterior disc height (PDH) were measured on preoperative, initial postoperative, and 3-month postoperative radiographs. PROMs including the Oswestry Disability Index (ODI); the visual analog scale (VAS); and pain portions of the EQ5D, VAS back, and VAS leg ratings were collected at the preoperative and subsequent postoperative visits. Length of hospital stay and postoperative complications related to the procedure were recorded. Results Significant improvements were seen at the initial (4.5° ± 8.6°, P < 0.001) and 3-month (4.4° ± 7.2°, P < 0.001) postoperative periods for LL, as well as SL (6.8° ± 4.8°, P < 0.001; 6.7° ± 4.4°, P < 0.001), ADH (8.0 mm ± 3.6, P < 0.001; 7.4 mm ± 3.6, P < 0.001), and PDH (3.3 mm ± 2.4, P < 0.001; 3.1 mm ± 2.5, P < 0.001). Significant improvements were seen at 3 months postoperatively for ODI (P < 0.001), EQ5D pain (P = 0.016), VAS leg (P < 0.001), and VAS back (P < 0.001). The average length of stay was 2.7 ± 4.5 days. The most common complications were ipsilateral thigh pain/numbness (45.1%), ipsilateral hip flexor weakness (39.0%), and contralateral thigh pain/numbness (14.6%). Conclusions While early PROMs and correction of sagittal radiographic parameters show promising results for the PTP approach for LLIF, it is not without risks. Clinical Relevance PTP interbody fusion is an emerging technique that allows for simultaneous access to the anterior and posterior columns of the lumbar spine. This early case series demonstrates significant improvement in functional outcomes and lumbar lordosis with a safety profile comparable to other well-established techniques. Level of Evidence 3.