Sample preparation for lipid analysis of intra-articular adipose tissue by using matrix-assisted laser desorption/ionization imaging.

Mass spectrometry imaging (MSI) is a powerful technique enabling the visualization of the spatial distribution of different molecules in tissue biopsies with different pathologies. Sample handling and preparing adipose tissue for MSI is challenging and prone to molecular delocalization due to tissue melting. In this work, we developed a method for matrix-assisted laser desorption/ionization (MALDI)-MSI to study lipids in human infrapatellar fat pad (IPFP), a biomarker source in musculoskeletal pathologies, while preserving molecular spatial distribution. Cryosectioning at 15 µm with a temperature below -30 °C, thaw-mounting, and sublimation, was demonstrated to preserve IPFP's heterogeneous appearance and spatial distribution of lipids.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) reveals potential lipid markers between infrapatellar fat pad biopsies of osteoarthritis and cartilage defect patients.

The incidence of osteoarthritis (OA) has been expected to increase due to an aging population, as well as an increased incidence of intra-articular (osteo-) chondral damage. Lipids have already been shown to be involved in the inflammatory process of OA. This study aims at revealing region-specific lipid profiles of the infrapatellar fat pad (IPFP) of OA or cartilage defect patients by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which could be used as biomarkers for early OA detection. A higher presence of phospholipids was found in OA patients compared with cartilage defect patients. In addition, a higher abundance of ether-linked phosphatidylethanolamines (PE O-s) containing arachidonic acid was specifically found in OA patients compared with cartilage defect patients. These lipids were mainly found in the connective tissue of the IPFP. Specific lipid species were associated to OA patients compared with cartilage defect patients. PE O-s have been suggested as possible biomarkers for OA. As these were found more abundantly in the connective tissue, the IPFP's intra-tissue heterogeneity might play an important role in biomarker discovery, implying that the amount of fibrous tissue is associated with OA.

The preferred technique for knee synovium biopsy and synovial fluid arthrocentesis.

For knee osteoarthritis and related conditions, analysis of biomarkers hold promise to improve early diagnosis and/or offer patient-specific treatment. To compare biomarker analyses, reliable, high-quality biopsies are needed. The aim of this work is to summarize the literature on the current best practices of biopsy of the synovium and synovial fluid arthrocentesis. Therefore, PubMed, Embase and Web of Science were systematically searched for articles that applied, demonstrated, or evaluated synovial biopsies or arthrocentesis. Expert recommendations and applications were summarized, and evidence for superiority of techniques was evaluated. Thirty-one studies were identified for inclusion. For arthrocentesis, the superolateral approach in a supine position, with a 0°-30° knee flexion was generally recommended. 18-gage needles, mechanical compression and ultrasound-guidance were found to give superior results. For blind and image-guided synovial biopsy techniques, superolateral and infrapatellar approaches were recommended. Single-handed tools were preconized, including Parker-Pearson needles and forceps. Sample quantity ranged approximately from 2 to 20. Suggestions were compiled for arthrocentesis regarding approach portal and patient position. Further evidence regarding needle size, ultrasound-guidance and mechanical compression were found. More comparative studies are needed before evidence-based protocols can be developed.

Limited evidence in support of bone marrow aspirate concentrate as an additive to the bone marrow stimulation for osteochondral lesions of the talus: a systematic review and meta-analysis.

PURPOSE: Bone marrow aspirate concentrate can be used as an additive to surgical treatment of osteochondral lesions of the talus. This systematic literature review aims to study the effect of the additional use of bone marrow aspirate concentrate on top of a surgical treatment for osteochondral lesions of the talus on clinical outcomes compared to surgical treatment alone. METHODS: An online literature search was conducted using PubMed (Medline), Embase (Ovid), and the Cochrane library for all studies comparing a surgical intervention with bone marrow aspirate concentrate, with a surgical intervention without bone marrow aspirate concentrate. The methodological quality was rated according to the methodological index for non-randomised studies checklist. The primary outcome measure were clinical outcomes. Secondary outcome measures consisted of revision rate, complication rate, radiographic outcome measures and histological analyses. Subgroups were created based on type of surgical intervention used in the studies. If multiple articles were included in a subgroup, a linear random-effects model was used to compare the bone marrow aspirate concentrate-augmented group with the control group. RESULTS: Out of 1006 studies found, eight studies with a total of 718 patients were included. The methodological quality, assessed according to the methodological index for non-randomised studies checklist, was weak. A significantly better functional outcome measures (p < 0.05) was found in the subgroup treated with bone marrow stimulation + bone marrow aspirate concentrate compared to the group treated with bone marrow stimulation alone, based on three non-blinded studies. No significant differences regarding clinical outcomes were found in the subgroups comparing matrix-induced autologous chondrocyte implantation with matrix-induced bone marrow aspirate concentrate, osteochondral autologous transplantation alone with osteochondral autologous transplantation + bone marrow aspirate concentrate and autologous matrix-induced chondrogenesis plus peripheral blood concentrate vs. matrix-associated stem cell transplantation bone marrow aspirate concentrate. CONCLUSION: There is insufficient evidence to support a positive effect on clinical outcomes of bone marrow aspirate concentrate as an additive to surgical treatment of osteochondral lesions of the talus. However, based on the safety reports and initial results, sufficiently powered, patient- and researcher-blinded, prospective randomised controlled trials are justified and recommended. Until then, we advise not to implement a therapy (addition of bone marrow aspirate concentrate) without clinical evidence that justifies the additional costs involved. LEVEL OF EVIDENCE: Level III.

Failure rates in surgical treatment in adults with bacterial arthritis of a native joint: a systematic review of 8,586 native joints.

INTRODUCTION: Most adult cases of bacterial-septic-arthritis of a native joint are effectively managed with a single surgical debridement, but some cases may require more than one debridement to control the infection. Consequently, this study assessed the failure rate of a single surgical debridement in adults with bacterial arthritis of a native joint. Additionally, risk factors for failure were assessed. MATERIALS AND METHODS: The review protocol was registered on PROSPERO (CRD42021243460) before data collection and conducted in line with the 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' (PRISMA) guidelines. Multiple libraries were systematically searched to identify articles including patients reporting on the incidence of failure (i.e. persistence of infection requiring reoperation) of the treatment of bacterial arthritis. The quality of individual evidence were assessed using the Quality in Prognosis Studies (QUIPS) tool. Failure rates were extracted from included studies and pooled. Risk factors for failure were extracted and grouped. Moreover, we evaluated which risk factors were significantly associated with failure. RESULTS: Thirty studies (8,586 native joints) were included in the final analysis. The overall pooled failure rate was 26% (95% CI 20 to 32%). The failure rate of arthroscopy and arthrotomy was 26% (95% CI 19 to 34%) and 24% (95% CI 17 to 33%), respectively. Seventy-nine potential risk factors were extracted and grouped. Moderate evidence was found for one risk factor (synovial white blood cell count), and limited evidence was found for five risk factors (i.e. sepsis, large joint infection, the volume of irrigation, blood urea nitrogen-test, and blood urea nitrogen/creatinine ratio). CONCLUSION: A single surgical debridement fails to control bacterial arthritis of a native joint in approximately a quarter of all adult cases. Limited to moderate evidence exists that risk factors associated with failure are: synovial white blood cell count, sepsis, large joint infection, and the volume of irrigation. These factors should urge physicians to be especially receptive to signs of an adverse clinical course.

Mass Spectrometry-based Biomarkers for Knee Osteoarthritis: A Systematic Review.

INTRODUCTION: Knee osteoarthritis (OA) is a joint disease, affecting multiple tissues in the joint. Early detection and intervention may delay OA development and avoid total knee arthroplasty. Specific biomarker profiles for early detection and guiding clinical decision-making of OA have not yet been identified. One technique that can contribute to the finding of this 'OA biomarker' is mass spectrometry (MS), which offers the possibility to analyze different molecules in tissues or fluids. Several proteomic, lipidomic, metabolomic and other - omic approaches aim to identify these molecular profiles; however, variation in methods and techniques complicate the finding of promising candidate biomarkers. AREAS COVERED: In this systematic review, we aim to provide an overview of molecules in knee OA patients. Possible biomarkers in several tissue types of OA and non-OA patients, as well as current limitations and possible future suggestions will be discussed. EXPERT OPINION: According to this review, we do not believe one specific biomarker will function as predictive molecule for OA. Likely, a group of molecules will give insight in OA development and possible therapeutic targets. For clinical implementation of MS-analysis in clinical decision-making, standardized procedures, large cohort studies and sharing protocols and data is necessary.

Biomechanical effects of a titanium intervertebral cage as a stand-alone device, and in combination with locking plates in the canine caudal cervical spine.

OBJECTIVE: To evaluate the change in ex vivo biomechanical properties of the canine cervical spine, due to an intervertebral cage, both as a stand-alone device and in combination with plates. STUDY DESIGN: Experimental ex vivo study. ANIMALS: Cervical spinal segments (C5-C7) from eight canine cadavers. METHODS: The range of motion (ROM) and elastic zone stiffness (EZS) of the spines were determined with a four-point bending device in flexion/extension, lateral bending, and axial rotation for four conditions: native, discectomy, cage (at C6-C7), and cage with plates (at C6-C7). The disc height index (DHI) for each condition was determined using radiography. RESULTS: Discectomy resulted in overall increased ROM (p < .01) and EZS (p < .05) and decreased DHI (p < .005) when compared to the native condition. Placement of the cage increased DHI (p < .001) and restored total ROM during flexion/extension, lateral bending and axial rotation, and EZS during flexion/extension to the level of the native spine. Application of the plates further reduced the total ROM during flexion/extension (p < .001) and lateral bending (p < .001), but restored ROM in extension and EZS during lateral bending. No implant failure, subsidence, or significant cage migration occurred during loading. CONCLUSION: An anchorless intervertebral cage used as a stand-alone device was able to restore the disc height and spinal stability to the level of the native cervical spine, whereas the addition of plates further reduced the spinal unit mobility. CLINICAL SIGNIFICANCE: This study implies that the intervertebral cage may be used as a stand-alone device in the spinal unit fixation in the canine cervical spine.

The biomechanical effect of single-level laminectomy and posterior instrumentation on spinal stability in degenerative lumbar scoliosis: a human cadaveric study.

OBJECTIVEDegenerative lumbar scoliosis, or de novo degenerative lumbar scoliosis, can result in spinal canal stenosis, which is often accompanied by disabling symptoms. When surgically treated, a single-level laminectomy is performed and short-segment posterior instrumentation is placed to restore stability. However, the effects of laminectomy on spinal stability and the necessity of placing posterior instrumentation are unknown. Therefore, the aim of this study was to assess the stability of lumbar spines with degenerative scoliosis, characterized by the range of motion (ROM) and neutral zone (NZ) stiffness, after laminectomy and placement of posterior instrumentation.METHODSTen lumbar cadaveric spines (T12-L5) with a Cobb angle ≥ 10° and an apex on L3 were included. Three loading cycles were applied per direction, from -4 Nm to 4 Nm in flexion/extension (FE), lateral bending (LB), and axial rotation (AR). Biomechanical evaluation was performed on the native spines and after subsequent L3 laminectomy and the placement of posterior L2-4 titanium rods and pedicle screws. Nonparametric and parametric tests were used to analyze the effects of laminectomy and posterior instrumentation on NZ stiffness and ROM, respectively, both on an individual segment's motion and on the entire spine section. Spearman's rank correlation coefficient was used to study the correlation between disc degeneration and spinal stability.RESULTSThe laminectomy increased ROM by 9.5% in FE (p = 0.04) and 4.6% in LB (p = 0.01). For NZ stiffness, the laminectomy produced no significant effects. Posterior instrumentation resulted in a decrease in ROM in all loading directions (-22.2%, -24.4%, and -17.6% for FE, LB, and AR, respectively; all p < 0.05) and an increase in NZ stiffness (+44.7%, +51.7%, and +35.2% for FE, LB, and AR, respectively; all p < 0.05). The same changes were seen in the individual segments around the apex, while the adjacent, untreated segments were mostly unaffected. Intervertebral disc degeneration was found to be positively correlated to decreased ROM and increased NZ stiffness.CONCLUSIONSLaminectomy in lumbar spines with degenerative scoliosis did not result in severe spinal instability, whereas posterior instrumentation resulted in a rigid construct. Also, prior to surgery, the spines already had lower ROM and higher NZ stiffness in comparison to values shown in earlier studies on nonscoliotic spines of the same age. Hence, the authors question the clinical need for posterior instrumentation to avoid instability.

Changes in Intervertebral Disk Mechanical Behavior During Early Degeneration.

Intervertebral disk (IVD) degeneration is commonly described by loss of height and hydration. However, in the first stage of IVD degeneration, this loss has not yet occurred. In the current study, we use an ex vivo degeneration model to analyze the changes in IVDs mechanical behavior in the first phase of degeneration. We characterize these changes by stretched-exponential fitting, and suggest the fitted parameters as markers for early degeneration. Enzymatic degeneration of healthy lumbar caprine IVDs was induced by injecting 100 µL of Chondroïtinase ABC (Cabc) into the nucleus. A no-intervention and phosphate buffered saline (PBS) injected group were used as controls. IVDs were cultured in a bioreactor for 20 days under diurnal, simulated-physiological loading (SPL) conditions. Disk deformation was continuously monitored. Changes in disk height recovery behavior were quantified using stretched-exponential fitting. Disk height, histological sections, and water- and glycosaminoglycan (GAG)-content measurements were used as gold standards for the degenerative state. Cabc injection caused significant GAG loss from the nucleus and had detrimental effects on poro-elastic mechanical properties of the IVDs. These were progressive over time, with a propensity toward more linear recovery behavior. On histological sections, both PBS and Cabc injected IVDs showed moderate degeneration. A small GAG loss yields changes in IVD recovery behavior, which can be quantified with stretched-exponential fitting. Parameters changed significantly compared to control. Studies on disk degeneration and biomaterial engineering for degenerative disk disease (DDD) could benefit from focusing on IVD biomechanical behavior rather than height and water-content, as a marker for early disk degeneration.

Functioning Without Cartilage: Older People With Radiographic Knee Osteoarthritis Who Self-Report No Functional Limitations Do Score Lower on a Performance Battery.

The majority of the older population shows signs of radiographic knee osteoarthritis. However, many remain without functional complaints for a long period. This study aims to find early functional changes associated with stages of radiographic knee osteoarthritis. A group of older people without self-reported complaints was divided in two groups: knee osteoarthritis (K&L = 2-4, N = 29) and control (K&L = 0-1, N = 31). Muscle function was assessed with voluntary and electrically-stimulated isometric knee contractions, including a fatigue test. Physical functioning was assessed with a 6-min walk test (6MWT), a stair climb test (SCT), and a short performance battery. There were no differences in muscle function parameters, 6MWT, and SCT between groups. A clinically relevant lower score on the performance battery was found in participants with knee osteoarthritis. In conclusion, even when older people indicate to have no functional limitations, a decline in functional outcome can be measured with a physical performance battery.

Fifteen out of 16 elite athletes showed concomitant low-grade cartilage lesions of the ankle with unstable syndesmotic injuries: concerns from a prospective case series.

Objectives: This study aimed to determine the incidence rate and characterise the location and severity of cartilage lesions in the ankle in elite athletes undergoing suture-button stabilisation for unstable distal syndesmotic injuries using needle arthroscopic examination. The feasibility and safety of ad hoc needle arthroscopy and its assisted interventions were also assessed. Methods: This prospective case series included elite athletes undergoing surgical stabilisation between April 2021 and June 2023. Procedures involved suture button fixation and needle arthroscopy, conducted by a single ankle fellow-trained surgeon. Ankle cartilage lesions were graded using the Cheng and Ferkel classification and located using the nine-zone grid. The study followed the STROBE statement. Results: This study included 16 elite athletes undergoing surgery for distal syndesmotic injuries, with 75% having acute and 25% chronic injuries. Cartilage lesions were prevalent (n=15/16, 94%), mainly at the talar dome (90%), and primarily scored as grade 1 (33%) or grade 2 (67%). Distal tibia cartilage damage occurred in 13% of cases. All patients were diagnosed with an instability of the syndesmosis confirmed through needle arthroscopy and were treated with a suture button (one or two buttons) fixation. Conclusion: In 15/16 elite athletes with syndesmotic injuries, concomitant ankle cartilage lesions were identified through needle arthroscopy. In addition, most of the lesions were classified as grade 1 or 2, denoting superficial damage. Needle arthroscopic interventions proved feasible and safe for confirming syndesmotic instability and addressing intra-articular pathologies.

Second-Look Arthroscopy Shows Inferior Cartilage after Bone Marrow Stimulation Compared with Other Operative Techniques for Osteochondral Lesions of the Talus: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare cartilage quality after different surgical interventions for osteochondral lesions of the talus (OLT), evaluated by second-look arthroscopy. Secondary aims were to report concomitant diagnoses, and to correlate cartilage quality with clinical and radiological outcomes. This review hypothesizes that the cartilage repair after bone marrow stimulation (BMS) is inferior to the other available treatment options. METHODS: PROSPERO ID: CRD42022311489. Studies were retrieved through PubMed, EMBASE (Ovid), and Cochrane Library. Studies were included if they reported cartilage quality after second-look investigation after surgical treatment of OLT. The primary outcome measure was the cartilage quality success and failure rates (%) per surgical intervention group. Correlations between the cartilage quality and clinical or radiological outcomes were calculated. RESULTS: Twenty-nine studies were included, comprising 586 ankles that had undergone second-look arthroscopy on average 16 months after initial surgery. The success rate for BMS was 57% (95% confidence interval [CI] = 48%-65%), for fixation (FIX) 86% (95% CI = 70%-94%), for osteo(chondral) transplantation (OCT) 91% (95% CI = 80%-96%), for cartilage implementation techniques (CITs) 80% (95% CI = 69%-88%), and for retrograde drilling 100% (95% CI = 66%-100%). The success rate of BMS was significantly lower than FIX, OCT, and CIT (P < 0.01). There were no significant differences between other treatment groups. A moderate positive significant correlation between the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score and the International Cartilage Repair Society score (ICRS) was found (ρ = 0.51, P < 0.001). CONCLUSIONS: Successful restoration of cartilage quality was found in the majority of surgically treated OLTs. However, BMS yields inferior cartilage quality compared with FIX, OCT, and CIT. Study Design. Systematic review and meta-analysis. Level of evidence. Level IV, systematic review and meta-analysis.

Reporting of Morphology, Location, and Size in the Treatment of Osteochondral Lesions of the Talus in 11,785 Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: Uniformity of reporting is a requisite to be able to compare results of clinical studies on the treatment of osteochondral lesions of the talus (OLT). The primary aim of this study was to evaluate the frequency and quality of reporting of size, morphology, and location of OLTs. DESIGN: A literature search was performed from 1996 to 2023 to identify clinical studies on surgical treatment of OLTs. Screening was performed by 2 reviewers, who subsequently graded the quality using the methodological index for non-randomized studies (MINORS). The primary outcome was the frequency and qualitative assessment of reporting of size, morphology, and location. RESULTS: Of 3,074 articles, 262 articles were included. This comprised a total of 11,785 patients. Size was reported in 248 (95%) of the articles and was described with a measure for surface area in 83%, however, in 56%, definition of measurement is unknown. Intraclass coefficient (ICC) value for the reliability of size measurement was 0.94 for computed tomography (CT) scan and 0.87 for MRI scan. Morphology was reported in 172 (66%) of the articles and using a classification system in 23% of the studies. Location was reported in 220 (84%) of the studies. CONCLUSION: No consensus was found on the reporting of morphology, with non-validated classification systems and different terminologies used. For location, reporting in 9 zones is underreported. Size was well reported and measurements are more reliable for CT compared with MRI. As these prognostic factors guide clinical decision-making, we advocate the development of a standardized and validated OLT classification to reach uniform reporting in literature. LEVEL OF EVIDENCE: Level III, systematic review.

Prognostic Factors for the Clinical Outcome after Microfracture Treatment of Chondral and Osteochondral Defects in the Knee Joint: A Systematic Review.

OBJECTIVE: The objective of this study is to establish which patient and lesion characteristics are related to the clinical outcome after microfracture of cartilage defects in the knee. STUDY DESIGN: Systematic review. METHODS: After preregistration, PubMed, Embase, and Cochrane were searched for studies that analyzed prognostic factors for the outcome of microfracture treatment in the knee. The criteria for inclusion were outcome measured using Patient-Reported Outcome Measures (PROMs), a clinical study with ≥10 participants receiving microfracture, and a minimal follow-up period of 1 year. RESULTS: For none of the investigated prognostic factors, effect size reporting was sufficiently homogeneous to conduct a meta-analysis. However, a majority of the included studies identified higher age, larger lesion size, longer preoperative symptom duration, and previous surgery on the ipsilateral knee, especially meniscectomy and anterior cruciate ligament reconstruction, as factors that are reported to be correlated to a less favorable outcome. A lesion location that does not include the trochlea or the patellofemoral joint and is not weightbearing, a nondegenerative mechanism of injury, and a single lesion were reported as factors that predict a favorable outcome. As to gender, body mass index, preoperative activity level, smoking, and concomitant knee surgery, the included articles were inconclusive or no effect was reported. CONCLUSIONS: Several factors correlated with the clinical result after microfracture treatment. However, the information on the effect sizes of the influence on clinical outcome is incomplete due to poor reporting. Large-scale registries or pooling of homogeneous, well-reported data is needed to work toward prognostic models. That would be an important step toward personalized treatment.

Near-Infrared Spectral Similarity between Ex Vivo Porcine and In Vivo Human Tissue.

BACKGROUND: In vivo diffuse reflectance spectroscopy provides additional contrast in discriminating nerves embedded in adipose tissue during surgery. However, large datasets are required to achieve clinically acceptable classification levels. This study assesses the spectral similarity between ex vivo porcine and in vivo human spectral data of nerve and adipose tissue, as porcine tissue could contribute to generate large datasets. METHODS: Porcine diffuse reflectance spectra were measured at 124 nerve and 151 adipose locations. A previously recorded dataset of 32 in vivo human nerve and 23 adipose tissue locations was used for comparison. In total, 36 features were extracted from the raw porcine to generate binary logistic regression models for all combinations of two, three, four and five features. Feature selection was performed by assessing similar means between normalized features of nerve and of adipose tissue (Kruskal-Wallis test, p < 0.05) and for models performing best on the porcine cross validation set. The human test set was used to assess classification performance. RESULTS: The binary logistic regression models with selected features showed an accuracy of 60% on the test set. CONCLUSIONS: Spectral similarity between ex vivo porcine and in vivo human adipose and nerve tissue was present, but further research is required.

Incidence, prevalence and nature of injuries in padel: a systematic review.

Objective: It is unclear what the incidence, prevalence and nature of injuries are that can occur during playing padel. This study aimed to systematically review the incidence, prevalence and nature of injuries in padel. Method: A literature search was performed up to December 2022 through MEDLINE Ovid, PubMed, Cochrane Library, SportsDiscus and CINAHL. Following database search, article retrieval and title and abstract screening, articles were assessed for eligibility against predefined criteria. Studies were assessed for methodological quality. Data on injuries' prevalence, incidence and nature of injuries were extracted, analysed and described in a descriptive statistical manner which did not include a pooling strategy as part of a formal meta-analysis. Results: Eight studies with 2022 participants were included (range of mean age: 31-57). The incidence rate was 3 injuries per 1000 hours of padel training and 8 injuries per 1000 matches of padel practice. The overall prevalence range was 40%-95%. The elbow was the most common anatomical site of injury, followed by the knee, shoulder and lower back. Tendinous and muscular injuries were the most reported injury types. Conclusion: Injuries are common among padel players, with an incidence rate of 3 per 1000 hours of padel training and 8 per 1000 matches of padel practice-as based on limited literature. The overall prevalence range was 40%-95%. The elbow was the most frequently reported anatomical region concerning location injury distribution, and injuries were mainly of tendinous or muscular origin.

Injectable biomaterial induces regeneration of the intervertebral disc in a caprine loaded disc culture model.

Back pain is the leading cause of disability with half of cases attributed to intervertebral disc (IVD) degeneration, yet currently no therapies target this cause. We previously reported an ex vivo caprine loaded disc culture system (LDCS) that accurately represents the cellular phenotype and biomechanical environment of human IVD degeneration. Here, the efficacy of an injectable hydrogel system (LAPONITE® crosslinked pNIPAM-co-DMAc, (NPgel)) to halt or reverse the catabolic processes of IVD degeneration was investigated within the LDCS. Following enzymatic induction of degeneration using 1 mg mL-1 collagenase and 2 U mL-1 chondroitinase ABC within the LDCS for 7 days, IVDs were injected with NPgel alone or with encapsulated human bone marrow progenitor cells (BMPCs). Un-injected caprine discs served as degenerate controls. IVDs were cultured for a further 21 days within the LDCS. Tissues were then processed for histology and immunohistochemistry. No extrusion of NPgel was observed during culture. A significant decrease in histological grade of degeneration was seen in both IVDs injected with NPgel alone and NPgel seeded with BMPCs, compared to un-injected controls. Fissures within degenerate tissue were filled by NPgel and there was evidence of native cell migration into injected NPgel. The expression of healthy NP matrix markers (collagen type II and aggrecan) was increased, whereas the expression of catabolic proteins (MMP3, ADAMTS4, IL-1ß and IL-8) was decreased in NPgel (±BMPCs) injected discs, compared to degenerate controls. This demonstrates that NPgel promotes new matrix production at the same time as halting the degenerative cascade within a physiologically relevant testing platform. This highlights the potential of NPgel as a future therapy for IVD degeneration.

The Frequency and Severity of Complications in Surgical Treatment of Osteochondral Lesions of the Talus: A Systematic Review and Meta-Analysis of 6,962 Lesions.

OBJECTIVE: The primary aim was to determine and compare the complication rate of different surgical treatment options for osteochondral lesions of the talus (OLTs). The secondary aim was to analyze and compare the severity and types of complications. DESIGN: A literature search was performed in MEDLINE (PubMed), EMBASE (Ovid), and the Cochrane Library. Methodological quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS). Primary outcome was the complication rate per surgical treatment option. Secondary outcomes included the severity (using the Modified Clavien-Dindo-Sink Complication Classification System for Orthopedic Surgery) and types of complications. The primary outcome, the severity, and the sub-analyses were analyzed using a random effects model. A moderator test for subgroup-analysis was used to determine differences. The types of complications were presented as rates. RESULTS: In all, 178 articles from the literature search were included for analysis, comprising 6,962 OLTs with a pooled mean age of 35.5 years and follow-up of 46.3 months. Methodological quality was fair. The overall complication rate was 5% (4%-6%; treatment group effect, P = 0.0015). Analysis resulted in rates from 3% (2%-4%) for matrix-assisted bone marrow stimulation to 15% (5%-35%) for metal implants. Nerve injury was the most observed complication. CONCLUSIONS: In 1 out of 20 patients treated surgically for an OLT, a complication occurs. Metal implants have a significantly higher complication rate compared with other treatment modalities. No life-threatening complications were reported.

Evaluation of the Anti-Inflammatory and Chondroprotective Effect of Celecoxib on Cartilage Ex Vivo and in a Rat Osteoarthritis Model.

OBJECTIVE: The potential chondroprotective effect of celecoxib, a nonsteroidal anti-inflammatory drug and selective cyclooxygenase-2 inhibitor used to reduce pain and inflammation in knee osteoarthritis patients, is disputed. This study aimed at investigating the chondroprotective effects of celecoxib on (1) human articular cartilage explants and (2) in an in vivo osteoarthritis rat model. DESIGN: Articular cartilage explants from 16 osteoarthritis patients were cultured for 24 hours with celecoxib or vehicle. Secreted prostaglandins (prostaglandin E2, prostaglandin F2α, prostaglandin D2) and thromboxane B2 (TXB2) concentrations were determined in medium by ELISA, and protein regulation was measured with label-free proteomics. Cartilage samples from 7 of these patients were analyzed for gene expression using real-time quantitative polymerase chain reaction. To investigate the chondroprotective effect of celecoxib in vivo, 14 rats received an intra-articular injection of celecoxib or 0.9% NaCl after osteoarthritis induction by anterior cruciate ligament transection and partial medial meniscectomy (ACLT/pMMx model). Histopathological scoring was used to evaluate osteoarthritis severity 12 weeks after injection. RESULTS: Secretion of prostaglandins, target of Nesh-SH3 (ABI3BP), and osteonectin proteins decreased, whereas tissue inhibitor of metalloproteinase 2 (TIMP-2) increased significantly after celecoxib treatment in the human (ex vivo) explant culture. Gene expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 (ADAMTS4/5) and metalloproteinase 13 (MMP13) was significantly reduced after celecoxib treatment in human cartilage explants. Cartilage degeneration was reduced significantly in an in vivo osteoarthritis knee rat model. CONCLUSIONS: Our data demonstrated that celecoxib acts chondroprotective on cartilage ex vivo and a single intra-articular bolus injection has a chondroprotective effect in vivo.