Early and non-invasive detection of osteoarthritis (OA) is required to enable early treatment and monitoring of interventions. Some of the earliest signs of OA are the change in proteoglycan and collagen composition. The aim of this study is to establish the relations between quantitative magnetic resonance imaging (MRI) and biochemical concentration and organization in knee articular cartilage. A preregistered systematic literature review was performed using the databases PubMed and Embase. Papers were included if quantitative MRI and a biochemical assay or polarized light microscopy (PLM) was performed on knee articular cartilage, and a quantified correlation was described. The extracted correlations were pooled using a random effects model. 21 papers were identified. The strongest pooled correlation was found for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) vs proteoglycan concentration (r = 0.59). T1ρ relaxation times are inversely correlated to proteoglycan concentration (r = -0.54). A weak correlation between T2 relaxation times and proteoglycans was found (r = -0.38). No correlation between T2 relaxation time and collagen concentration was found (r = -0.02). A heterogeneous set of correlations between T2 relaxation times and PLM were identified, including strong correlations to anisotropy. DGEMRIC measures are significantly correlated to proteoglycan concentration. The needed contrast agent is however a disadvantage; the T1ρ sequence was found as a non-invasive alternative. Remarkably, no correlation was found between T2 relaxation times and collagen concentration. T2 relaxation times is related to organization, rather than concentration of collagen fibers. CRD42020168337.

Objective The aim of the study was to determine the diagnostic accuracy of imaging modalities to detect pseudarthrosis after thoracolumbar spinal fusion, with surgical exploration as reference standard. Materials and methods A systematic literature search for original studies was performed on the diagnostic accuracy of imaging as index test compared to surgical exploration as reference standard to diagnose pseudarthrosis after thoracolumbar spinal fusion. Diagnostic accuracy values were extracted and methodologic quality of studies was evaluated by the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Per modality, clinically comparable studies were included in subgroup meta-analysis and weighted odds ratios (ORs) were calculated using the random effects model. Results Fifteen studies were included. Risk of bias was classified as high/unclear in 58% of the studies. Concerns of applicability was classified as high/unclear in 40% of the studies. Four scintigraphy studies including 93 patients in total were pooled to OR = 2.91 (95% confidence interval [CI]: 0.93–9.13). Five studies on plain radiography with 398 patients in total were pooled into OR = 7.07 (95% CI: 2.97–16.86). Two studies evaluating flexion-extension radiography of 75 patients in total were pooled into OR = 4.00 (95% CI: 0.15–105.96). Two studies of 68 patients in total were pooled for CT and yielded OR = 17.02 (95% CI: 6.42–45.10). A single study reporting on polytomography, OR = 10.15 (95% CI 5.49–18.78), was also considered to be an accurate study. Conclusions With a pooled OR of 17.02, CT can be considered the most accurate imaging modality for the detection of pseudarthrosis after thoracolumbar spinal fusion from this review.

Electrospun (ESP) scaffolds are a promising type of tissue engineering constructs for large defects with limited depth. To form new functional tissue, the scaffolds need to be infiltrated with cells, which will deposit extracellular matrix. However, due to dense fiber packing and small pores, cell and tissue infiltration of ESP scaffolds is limited. Here, we combine two established methods, increasing fiber diameter and co-spinning sacrificial fibers, to create a porous ESP scaffold that allows robust tissue infiltration. Full cell infiltration across 2 mm thick scaffolds is seen 3 weeks after subcutaneous implantation in rats. After 6 weeks, the ESP scaffolds are almost fully filled with de novo tissue. Cell infiltration and tissue formation in vivo in this thickness has not been previously achieved. In addition, we propose a novel method for in vitro cell seeding to improve cell infiltration and a model to study 3D migration through a fibrous mesh. This easy approach to facilitate cell infiltration further improves previous efforts and could greatly aid tissue engineering approaches utilizing ESP scaffolds. Statement of significance: Electrospinning creates highly porous scaffolds with nano- to micrometer sized fibers and are a promising candidate for a variety of tissue engineering applications. However, smaller fibers also create small pores which are difficult for cells to penetrate, restricting cells to the top layers of the scaffolds. Here, we have improved the cell infiltration by optimizing fiber diameter and by co-spinning a sacrificial polymer. We developed novel culture technique that can be used to improve cell seeding and to study cytokine driven 3D migration through fibrous meshes. After subcutaneous implantation, infiltration of tissue and cells was observed up to throughout up to 2 mm thick scaffolds. This depth of infiltration in vivo had not yet been reported for electrospun scaffolds. The scaffolds we present here can be used for in vitro studies of migration, and for tissue engineering in defects with a large surface area and limited depth.

Background: Posterior lumbar interbody fusion (PLIF) is a surgical procedure to treat painful unstable spinal segments using bone graft filled interbody cages and instrumentation. The graft can be autologous bone or a bone substitute. RegenOss is a porous, 3-dimensional composite bone substitute consisting of collagen fibers including hydroxyapatite. The aim of this cohort study was to evaluate RegenOss as graft material in PLIF patients, as compared to a historical cohort grafted with autologous bone. Methods: Fifteen patients were enrolled prospectively at the Maastricht University Medical Center between November 2016 and May 2019 in the RegenOss cohort (METC14-1-056) and were compared to 15 matched prospective patients from a historical autologous cohort collected at the Maastricht University Medical Center between October 2011 and January 2014 (METC10-1-025). During PLIF, interbody cages were filled with RegenOss bone substitute in the RegenOss cohort and with local autologous bone in the autologous cohort. Both cohorts were subjected to patient reported outcome measures (PROMs) [including Oswestry Disability Index (ODI), Visual Analogue Scale (VAS), EuroQol-5D (EQ-5D)], 18F-fluoride positron emission tomography/computed tomography (PET/CT) at six weeks and one year. Interbody fusion was assessed on CT at one year and bone metabolism on 18F-fluoride PET/CT was assessed at six weeks and one year. Differences in patient demographics, clinical outcome, interbody fusion and bone metabolism were assessed between graft cohorts. Bone metabolism was also compared between follow-up moments. Results: Patient demographics were comparable between cohorts. At one-year follow-up, clinical outcome in both cohorts was similar (ODI: P=0.12, VAS: P=0.15, EQ-5D: P=0.22). Interbody fusion was considered comparable between cohorts; 7/15 RegenOss patients and 8/15 autologous patients were scored as completely fused on CT at one year. Similar findings in bone metabolism between follow-up moments were found for both cohorts; bone metabolism in the operated segment was significantly lower at one year compared to at six weeks (RegenOss cohort: P=0.003, P=0.005 for the upper and lower endplate respectively, autologous cohort: P=0.001, P=0.001). No differences in bone metabolism were observed between cohorts. Conclusions: Bony bridging, clinical outcome, bone metabolism were comparable for the RegenOss and the autologous bone graft PLIF cohorts.

Background: Identifying the cause of recurrent or persisting pain after posterior lumbar interbody fusion (PLIF) is essential for establishing optimal treatment. In this study, we evaluate patients after PLIF surgery by ¹⁸F-fluoride PET/CT scans and patient-reported outcome measures (PROMs). Methods: A total of 36 PLIF patients were included. Sixty minutes after intravenous injection of ¹⁸F-fluoride, PET/CT scanning was performed. Bone graft ingrowth, subsidence, screw loosening and damage of facet joints were scored by quantifying the level of bone metabolism of the vertebral endplates in the disc spaces, around screws and around the facet joints on the PET scans. Results: In contrast to asymptomatic patients, symptomatic patients showed abnormal PET values around pedicle screws and/or facet joints and at the lower endplates of the disc spaces, identifying a possible source of pain. On CT, no significant differences between these two groups were found. Conclusion: The PET/CT findings appeared to correlate better with symptoms on PROMs compared to CT findings alone. When interpreting ¹⁸F-fluoride PET/CT findings after PLIF surgery, one should realize bone metabolism in the disc spaces of the operated segments and around pedicle screws or facet joint changes during follow-up, reflecting natural recovery.

Posterior Lumbar Interbody Fusion (PLIF) is a surgical procedure in which stabilization of spinal segments is achieved by inserting interbody cages filled with bone graft. Positron Emission Tomography (PET) is an imaging modality to assess physiological processes at cellular level, well before manifestation of morphological changes on computed tomography (CT). The goal was to determine whether 18F-fluoride PET/CT findings six weeks after PLIF, can predict bony fusion one year postoperatively on CT. 20 consecutive PLIF patients (21 levels) were prospectively included. Based on diagnostic CT one year postoperatively, operated segments were classified as pseudarthrotic or fused. 18F-fluoride PET/CT scanning was performed at six weeks and one year, yielding parameters related to overall bone metabolism, bone blood flow and bone mineral incorporation. Differences in PET parameters between groups and follow-up moments were assessed. The area under the curve from the receiver operating characteristic was calculated for each PET parameter as a measure of diagnostic accuracy. 11 segments were classified as pseudarthrotic and 10 as fused. Pseudarthrotic segments showed lower intervertebral overall bone metabolism values compared to fused segments at six weeks. Pseudarthrotic segments showed lower intervertebral bone blood flow at six weeks and lower intervertebral bone mineral incorporation at one year compared to fused segments. Overall bone metabolism of the operated intervertebral disc space at six weeks had the highest diagnostic accuracy for predicting the fusion status at one year. 18F-fluoride PET/CT six weeks after PLIF provides prognostic information on bony fusion at one year.