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Objectives: Cartilage defects (CDs) are regarded as early manifestation of osteoarthritis (OA). The infrapatellar fat pad (IPFP) is an important mediator in maintaining joint homeostasis, disease progression and tissue repair, with a crucial role of its secreted proteins. Here, we investigate the proteome of the IPFP in relation to clinical status and response to surgical treatment of CDs., Methods: In order to characterize the proteome of the IPFP, samples from a cohort of 53 patients who received surgical treatment for knee CDs were analyzed with label-free proteomics. Patients were divided based on validated outcome scores for pain and knee function, preoperatively and at 1-year postoperatively, and on MRI assessment of the defect severity, fibrosis and synovitis., Results: Specific proteins were differentially abundant in patients with MRI features and better clinical outcome after CD surgery, including a downregulation of cartilage intermediate layer protein 2 (CILP-2) and microsomal glutathione s-transferase 1 (MGST1), and an upregulation of aggrecan (ACAN), and proteoglycan 4 (PRG4). Pathways related to cell interaction, oxidation and matrix remodeling were altered., Conclusion: Proteins in the IPFP that have a function in extracellular matrix, inflammation and immunomodulation were identified as potentially relevant markers for cartilage repair monitoring.

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., Competing Interests: Competing interests: Department of Orthopedic Surgery and Sports Medicine, Amsterdam University MedicalCenter, reports financial support that was provided by Arthrex. GK reports financial support was provided by Arthrex. GK reports arelationship with Arthrex that includes: consulting or advisory. The other authors, theydeclare that they have no known competing financial interests or personal relationships thatcould have appeared to influence the work reported in this paper., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

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., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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-1β 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.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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.

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., Competing Interests: Declaration of competing interest MH, KE, GT, RH, PE, and BCP are supported by the Dutch Research Council (NWO) domain Applied and Engineering Sciences (P15-23). MH, BC, RH, and BCP are supported by the Dutch Province of Limburg through the LINK (Limburg Investeert in haar Kenniseconomie) program. PE and BCP are supported by the Dutch Arthritis Society. PE has got a speaker consultancy fee paid to institute by Episurf and Arthrex (support for attending meeting). PE is involved with participation on a Data Safety Monitoring Board or Advisory Board (paid to institute) by Expert panel for Atro-Medical and Advisory board of TETEC AG. PE is vice chair of the international registree committee for joint-preserving surgery of the ICRS (no payments). PE is shareholder in Chondropeptix and Avalanche Medical., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

Objective: The aim of this study was to investigate early radiological and clinical outcome of autologous minced cartilage treatment as a single-step treatment option in patients with a chondral or osteochondral lesion (OCL) in the knee., Design: Eighteen patients with an OCL in the knee were included. Cartilage from healthy-appearing loose bodies and/or the periphery of the defect were minced into small chips and sealed in the defect using fibrin glue. Preoperatively, and at 3 ( n = 14) and 12 ( n = 18) months follow-up, magnetic resonance imaging (MRI) was performed. The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 score was used to assess the cartilage repair tissue on MRI at 12 months. The International Knee Documentation Score, Knee Injury and Osteoarthritis Outcome Score, EuroQoL-5D, and Visual Analogue Scale pain were collected preoperatively and 12 months after surgery., Results: Three months postoperative, MRI showed complete defect filling in 11 out of 14 patients. Mean MOCART 2.0 score at 12 months was 65.0 ± 18.9 with higher scores for lateral femoral chondral lesions compared to medial femoral chondral lesions (75.8 ± 14.3, 52.5 ± 15.8 respectively, P = 0.02). Clinical and statistical significant improvements were observed in the patient-reported outcome measures at 12 months postoperatively compared to preoperatively., Conclusion: Treatment of OCLs using the autologous minced cartilage procedure resulted in good cartilage repair measured by MOCART 2.0. Clinically relevant improvements were observed in the clinical scores. This study suggests autologous minced cartilage as a promising, single-step treatment for OCLs.

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 E 2 , prostaglandin F 2α , prostaglandin D 2 ) 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 .

Objective: 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., Methods: 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., Results: 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., Conclusion: 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., Prospero Id: CRD42020168337., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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.

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., (© 2021 The Authors. Veterinary Surgery published by Wiley Periodicals LLC on behalf of American College of Veterinary Surgeons.)

Degenerative lumbar scoliosis presumably alters spinal biomechanics, but a lack of quantitative reference measurements of these spines exists. We aimed to assess the biomechanical properties of spines with degenerative scoliosis, and to relate these to intervertebral disc degeneration (DD) and Cobb angle. Secondly, we compared these results to previous measurements of non-scoliotic spines. Ten cadaveric spines (Th12-L5, mean age 82 ± 11 years) with Cobb angle ≥10° and apex at L3 were acquired. Three loading cycles (-4 to 4 Nm) were applied in flexion/extension (FE), lateral bending (LB), and axial rotation (AR). The range of motion (ROM), neutral zone (NZ) stiffness, NZ ROM, elastic zone (EZ) stiffness and hysteresis were calculated for each motion segment in the loading direction. ROM was calculated in coupled directions, expressed as a percentage of rotation in the loaded direction. For Th12-L5, there was a ROM (degrees ± SD) of 14.9 ± 6.5 in FE, 14.9 ± 7.8 in LB, and 10.2 ± 5.5 in AR. The median (Nm/degree (Q1;Q3)) NZs was 0.24 (0.19;0.35) in FE, 0.25 (0.22;0.42) in LB, and 0.49 (0.33;0.99) in AR. Greater coupled motions related to higher Cobb angle, especially during AR on segments around the apex (FE: ρ = 0.539, p = 0.021 and LB: ρ = 0.821, p = 0.000). DD correlated to lower ROM and increased NZs on L2-L3 in FE (ρ = -0.721, p = 0.028 and ρ = 0.694, p = 0.038, respectively). Compared to non-scoliotic spines, smaller ROM in FE (p = 0.030) was found. This study describes the biomechanical properties of lumbar spines with degenerative scoliosis. Compared to non-scoliotic spines, they tended to be stiffer and exhibited smaller ROM in FE. DD only affected the ROM and NZs of the segments around the apex., Competing Interests: Declaration of Competing Interest None of the authors has a conflict of interest regarding this work., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Possible regenerative treatments for lumbar intervertebral disc degeneration (DD) are rapidly emerging. There is consensus that the patient that would benefit most has early-stage DD, with a predicted deterioration in the near future. To identify this patient, the aim of this study was to identify prognostic factors for progression of DD., Study Design: Systematic review., Methods: A systematic search was performed on studies evaluating one or more prognostic factor(s) in the progression of DD. The criteria for inclusion were (a) patients diagnosed with DD on MRI, (b) progression of DD at follow-up, and (c) reporting of one or more prognostic factor(s) in progression of DD. Two authors independently assessed the methodological quality of the included studies. Due to heterogeneity in DD determinants and outcomes, only a best-evidence synthesis could be conducted., Results: The search generated 3165 references, of which 16 studies met our inclusion criteria, involving 2.423 patients. Within these, a total of 23 clinical and environmental and 12 imaging factors were identified. There was strong evidence that disc herniation at baseline is associated with progression of DD at follow-up. There is limited evidence that IL6 rs1800795 genotype G/C male was associated with no progression of DD. Some clinical or environmental factors such as BMI, occupation and smoking were not associated with progression., Conclusions: Disc herniation is strongly associated with the progression of DD. Surprisingly, there was strong evidence that smoking, occupation, and several other factors were not associated with the progression of DD. Only one genetic variant may have a protective effect on progression, otherwise there was conflicting or only limited evidence for most prognostic factors. Future research into these prognostic factors with conflicting and limited evidence is not only needed to determine which patients should be targeted by regenerative therapies, but will also contribute to spinal phenotyping., Competing Interests: The authors declare no potential conflict of interest., (© 2019 The Authors. JOR Spine published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society.)

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.

Intervertebral disc degeneration describes the vicious cycle of the deterioration of intervertebral discs and can eventually result in degenerative disc disease (DDD), which is accompanied by low-back pain, the musculoskeletal disorder with the largest socioeconomic impact world-wide. In more severe stages, intervertebral disc degeneration is accompanied by loss of joint space, subchondral sclerosis, and osteophytes, similar to osteoarthritis (OA) in the articular joint. Inspired by this resemblance, we investigated the analogy between human intervertebral discs and articular joints. Although embryonic origin and anatomy suggest substantial differences between the two types of joint, some features of cell physiology and extracellular matrix in the nucleus pulposus and articular cartilage share numerous parallels. Moreover, there are great similarities in the response to mechanical loading and the matrix-degrading factors involved in the cascade of degeneration in both tissues. This suggests that the local environment of the cell is more important to its behavior than embryonic origin. Nevertheless, OA is widely regarded as a true disease, while intervertebral disc degeneration is often regarded as a radiological finding and DDD is undervalued as a cause of chronic low-back pain by clinicians, patients and society. Emphasizing the similarities rather than the differences between the two diseases may create more awareness in the clinic, improve diagnostics in DDD, and provide cross-fertilization of clinicians and scientists involved in both intervertebral disc degeneration and OA., Competing Interests: The authors have no conflicts of interest to report. Author contributionsAll authors have contributed to the manuscript and approved the final version.

So far, the relationship between wind and athletics performance has been studied mainly for 100 m sprint, based on simulation of biomechanical models, requiring several assumptions. In this study, this relationship is quantified empirically for all five horizontal jump and sprint events where wind is measured, with freely available competition results. After systematic scraping several elite and sub-elite results sites, the obtained results (n = 150,169) were filtered and matched to athletes. A quadratic mixed effects model with athlete and season as random effects was applied to express the influence of wind velocity on performance in each event. Whether this effect differs with performance level was investigated by applying the model on subgroups based on performance level. In the fitted quadratic model, the linear coefficients were significant (p < .001) for all events; the quadratic coefficients were significant for all events (p < .001) except long jump (p = .138). A 2.0 m s -1 tail wind provides an average advantage of 0.125, 0.140 and 0.146-s for the 100, 200 and 100/110 m hurdles, respectively, and an advantage of 0.058 and 0.102 m for long jump and triple jump, respectively. Performance level had a significant effect on the wind influence only for 100 m (p < .001). Amateur athletes (∼13 s) benefit 69% more from a 2.0 m s -1 tail wind than elite athletes (∼10 s). Practical formulas are presented for each event. These can easily be used correct results for wind speed, allowing better talent scouting and championship selection. This study demonstrates the efficacy of answering scientific questions empirically, through freely available data.

Objective: Mechanical overloading induces a degenerative cell response in the intervertebral disc. However, early changes in the extracellular matrix (ECM) are challenging to assess with conventional techniques. Fourier Transform Infrared (FTIR) imaging allows visualization and quantification of the ECM. We aim to identify markers for disc degeneration and apply these to investigate early degenerative changes due to overloading and katabolic cell activity., Design: Three experiments were conducted; Exp 1.: In vivo, lumbar spines of seven goats were operated: one disc was injected with chondroitinase ABC [cABC (mild degeneration)] and compared to the adjacent disc (control) after 24 weeks. Exp 2a: Ex vivo, caprine discs received physiological loading (n = 10) or overloading (n = 10) in a bioreactor. Exp 2b: Cell activity was diminished prior to testing by freeze-thaw cycles, 18 discs were then tested as in Exp 2a. In all experiments, FTIR images (spectral region: 1000-1300 cm -1 ) of mid-sagittal slices were analyzed using multivariate curve resolution., Results: In vivo, FTIR was more sensitive than biochemical and histological analysis in identifying reduced proteoglycan content (P = 0.046) and increased collagen content in degenerated discs (P < 0.01). Notably, FTIR analysis additionally showed disorganization of the ECM, indicated by increased collagen entropy (P = 0.011). Ex vivo, the proteoglycan/collagen ratio decreased due to overloading (P = 0.047) and collagen entropy increased (P = 0.047). Cell activity affected collagen content only (P = 0.044)., Conclusion: FTIR imaging allows a more detailed investigation of early disc degeneration than traditional measures. Changes due to mild overloading could be assessed and quantified. Matrix remodeling is the first detectable step towards intervertebral disc degeneration., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

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.

The intervertebral disc faces high compressive forces during daily activities. Axial compression induces creeping fluid loss and reduction in disc height. With degeneration, disc fluids and height are progressively lost, altering biomechanics. It is assumed that this reduction of fluids is caused by a decline of osmolality within the disc due to proteoglycan depletion. Here we investigate the isolated effect of a reduction in osmosis on the biomechanical properties of the intervertebral disc. Continuous diurnal loading was applied to healthy caprine intervertebral discs in a loaded disc culture system for a total of 6days. We increased testing bath osmolality with two doses of polyethylene-glycol (PEG), thereby reducing the osmotic gradient between the disc and the surrounding fluid. This way we could study the isolated effect of reduced osmosis on axial creep, without damaging the disc. We evaluated: daily creep and recovery, recovery time-constants and compressive stiffness. Additionally, we investigated water content. There was a strong dose-dependent effect of PEG concentration on water content and axial creep behaviour: disc height, amplitude and rate of creep and recovery were all significantly reduced. Axial compressive stiffness of the disc was not affected. Reduction of water content and amplitude of creep and recovery showed similarity to degenerative disc biomechanics. However, the time-constants increased, indicating that the hydraulic permeability was reduced, in contrast to what happens with degeneration. This suggests that besides the osmotic gradient, the permeability of the tissues determines healthy intervertebral disc biomechanics., (Copyright © 2017. Published by Elsevier Ltd.)

The mechanical behaviour of the intervertebral disc highly depends on the content and transport of interstitial fluid. It is unknown, however, to what extent the time-dependent behaviour can be attributed to osmosis. Here we investigate the effect of both mechanical and osmotic loading on water content, nucleus pressure and disc height. Eight goat intervertebral discs, immersed in physiological saline, were subjected to a compressive force with a pressure needle inserted in the nucleus. The loading protocol was: 10 N (6 h); 150 N (42 h); 10 N (24 h). Half-way the 150 N-phase (24 h), we eliminated the osmotic gradient by adding 26% poly-ethylene glycol to the surrounding fluid. For 62 additional discs, we determined the water content of both nucleus and annulus after 6, 24, 48, or 72 h. The compressive load was initially counterbalanced by the hydrostatic pressure in the nucleus. The load forced 4.3% of the water out of the nucleus, which reduced nucleus pressure by 44(±6)%. Reduction of the osmotic gradient disturbed the equilibrium disc height, and a significant loss of annulus water content was found. Remarkably, pressure and water content of the nucleus pulposus remained unchanged. This shows that annulus water content is important in the response to axial loading. After unloading, in the absence of an osmotic gradient, there was substantial viscoelastic recovery of 53(±11)% of the disc height, without a change in water content. However, for restoration of the nucleus pressure and for full restoration of disc height, restoration of the osmotic gradient was needed., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Mechanical loading is inherently related to the function and degeneration of the intervertebral disc. We present a series of experiments aimed at measuring the effect of a loading/unloading cycle of the intervertebral disc on the mechanical properties of the nucleus pulposus. The study relies on our new minimally invasive microindenter, which allows us to quantify the storage and loss moduli of the nucleus pulposus by inserting an optomechanical probe in an intact (resected) intervertebral disk through the annulus fibrosis via a small needle. Our results indicate that, under the influence of compressive loading, the nucleus pulposus exhibits a more solid-like behavior., Competing Interests: D.I. is co‐founder and shareholder of Optics11.

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.

Experiments regarding the mechanical properties of soft tissues mostly rely on data collected on specimens that are extracted from their native environment. During the extraction and in the time period between the extraction and the completion of the measurements, however, the specimen may undergo structural changes which could generate unwanted artifacts. To further investigate the role of mechanics in physiology and possibly use it in clinical practices, it is thus of paramount importance to develop instruments that could measure the viscoelastic response of a tissue without necessarily excising it. Tantalized by this opportunity, we have designed a minimally invasive micro-indenter that is able to probe the mechanical response of soft tissues, in situ, via an 18G needle. Here, we discuss its working principle and validate its usability by mapping the viscoelastic properties of a complex, confined sample, namely, the nucleus pulposus of the intervertebral disc. Our findings show that the mechanical properties of a biological tissue in its local environment may be indeed different than those that one would measure after excision, and thus confirm that, to better understand the role of mechanics in life sciences, one should always perform minimally invasive measurements like those that we have here introduced.

Study Design: Biomechanical study., Objective: Recently, a posterior concave periapical distraction device for fusionless scoliosis correction was introduced. The goal of this study was to quantify the effect of the periapical distraction device on spinal range of motion (ROM) in comparison with traditional rigid pedicle screw-rod instrumentation., Methods: Using a spinal motion simulator, 6 human spines were loaded with 4 N m and 6 porcine spines with 2 N m to induce flexion-extension (FE), lateral bending (LB), and axial rotation (AR). ROM was measured in 3 conditions: untreated, periapical distraction device, and rigid pedicle screw-rod instrumentation., Results: The periapical distraction device caused a significant ( P < .05) decrease in ROM of FE (human, -40.0% and porcine, -55.9%) and LB (human, -18.2% and porcine, -17.9%) as compared to the untreated spine, while ROM of AR remained unaffected. In comparison, rigid instrumentation caused a significantly ( P < .05) larger decrease in ROM of FE (human, -80.9% and porcine, -94.0%), LB (human, -75.0% and porcine, -92.2%), and AR (human, -71.3% and porcine, -86.9%)., Conclusions: Although no destructive forces were applied, no device failures were observed. Spinal ROM was significantly less constrained by the periapical distraction device compared to rigid pedicle screw-rod instrumentation. Therefore, provided that scoliosis correction is achieved, a more physiological spinal motion is expected after scoliosis correction with the posterior concave periapical distraction device., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: To properly study knee kinetics, kinematics and the effects of injury and surgical treatment in vitro, the knee should be constrained as little as possible, while imposing physiological loads. A novel dynamic biomechanical knee system (BKS) is presented here. The aim of this study was to test the feasibility and reproducibility of the system and demonstrate its features with an Anterior Cruciate Ligament (ACL) lesion model., Methods: Six goat knees were used in the current study. Flexion and extension simulating gait was imposed by a servo-motor, while normal joint load was applied by two artificial muscles. Intra-class correlation coefficients (ICCs) were assessed for inter-test measures, while paired t-tests were performed for comparison between intact knees and knees with ACL-lesion., Results: The ICC's for inter-test measures based on all six goat knees were excellent: varus/valgus: ICC=0.93; rotation: ICC=0.94 (all p<0.01), and translation in frontal (x)-, side (y)- and upward (z)-direction (ICC=0.90, 0.88 & 0.94) (all p<0.01). A significant increase in joint center movement was found in knees after creating an ACL-lesion (p=0.018): translation increased more than two-fold in frontal (p=0.016), side (p=0.004) and upward (p=0.018) direction., Conclusions: Five degrees of motion were reproducibly assessed in the intact joint, suggesting that the goat knee may find its natural pathway when loaded in the BKS. The novel five-degrees-of-freedom knee system allows a detailed study of the effect of a diversity of defects and surgical treatments on knee biomechanics under physiological loading conditions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Diurnal disc height changes, due to fluid in- and outflow, are in equilibrium while daytime spinal loading is twice as long as night time rest. A direction-dependent permeability of the endplates, favouring inflow over outflow, reportedly explains this; however, fluid flow through the annulus fibrosus should be considered. This study investigates the fluid flow of entire intervertebral discs. Caprine discs were preloaded in saline for 24h under four levels of static load. Under sustained load, we modulated the disc׳s swelling pressure by exchanging saline for demineralised water (inflow) and back to saline (outflow), both for 24h. We measured disc height creep and used stretched exponential models to determine time-constants. During inflow disc height increased in relation to applied load, and during outflow disc height decreased to preload levels. When comparing in- and outflow phases, there was no difference in creep, and time-constants were similar indicating no direction-dependent resistance to fluid flow in the entire intervertebral disc. Results provoked a new hypothesis for diurnal fluid flow: in vitro time-constants for loading are shorter than for unloading and in vivo daytime loading is twice as long as night time unloading, i.e. in diurnal loading the intervertebral disc is closer to loading equilibrium than to unloading equilibrium. Per definition, fluid flow is slower close to equilibrium than far from equilibrium; therefore, as diurnal loading occurs closer to loading equilibrium, fluid inflow during night time unloading can balance fluid outflow during daytime loading, despite a longer time-constant., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Nucleus pulposus replacement therapy could offer a less invasive alternative to restore the function of moderately degenerated intervertebral discs than current potentially destructive surgical procedures. Numerous nucleus pulposus substitutes have already been investigated, to assess their applicability for intradiscal use. Still, the current choice of testing methods often does not lead to efficient translation into clinical application. In this paper, we present the evaluation of a novel nucleus pulposus substitute, consisting of a hydromed core and an electrospun envelope. We performed three mechanical evaluations and an in vivo pilot experiment. Initially, the swelling pressure of the implant was assessed in confined compression. Next, we incorporated the implant into mechanically damaged caprine lumbar intervertebral discs to determine biomechanical segment behaviour in bending and torsion. Subsequently, segments were serially tested in native, damaged and repaired conditions under dynamic axial compressive loading regimes in a loaded disc culture system. Finally, nucleus pulposus substitutes were implanted in a live goat spine using a transpedicular approach. In confined compression, nucleus pulposus samples as well as implants showed some load-bearing capacity, but the implant exhibited a much lower absolute pressure. In bending and torsion, we found that the nucleus pulposus substitute could partly restore the mechanical response of the disc. During dynamic axial compression in the loaded disc culture system, on the other hand, the implant was not able to recover axial compressive behaviour towards the healthy situation. Moreover, the nucleus pulposus substitutes did not remain in place in the in vivo situation but migrated out of the disc area. From these results, we conclude that implants may mimic native disc behaviour in simple mechanical tests, yet fail in other, more realistic set-ups. Therefore, we recommend that biomaterials for nucleus pulposus replacement be tested in testing modalities of increasing complexity and in their relevant anatomical surroundings, for a more reliable prediction of clinical potential., (© The Author(s) 2015.)

Intervertebral disc degeneration is a major cause of low back pain. Despite its long history and large socio-economical impact in western societies, the initiation and progress of disc degeneration is not well understood and a generic disease model is lacking. In literature, mechanics and biology have both been implicated as the predominant inductive cause; here we argue that they are interconnected and amplify each other. This view is supported by the growing awareness that cellular physiology is strongly affected by mechanical loading. We propose a vicious circle of mechanical overloading, catabolic cell response, and degeneration of the water-binding extracellular matrix. Rather than simplifying the disease, the model illustrates the complexity of disc degeneration, because all factors are interrelated. It may however solve some of the controversy in the field, because the vicious circle can be entered at any point, eventually leading to the same pathology. The proposed disease model explains the comparable efficacy of very different animal models of disc degeneration, but also helps to consider the consequences of therapeutic interventions, either at the cellular, material or mechanical level., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

The intervertebral disc (IVD) allows flexibility to the vertebral column, and transfers the predominant axial loads during daily activities. Its axial biomechanical behaviour is poroelastic, due to the water-binding and releasing capacity of the nucleus pulposus. Degeneration of the intervertebral disc presumably affects both the instantaneous elastic response to the load on the IVD and the subsequent interstitial flow of fluid. This study aims to quantify the poroelastic behaviour of the IVD and its change with degeneration, as defined by the magnetic resonance imaging-based Pfirrmann Score (PS). For a period of ten days, 36 human lumbar IVDs were loaded with a simulated physiological axial loading regime, while deformation was monitored. The IVDs responded to the loads with instantaneous elastic and slow poroelastic axial deformation. Several mechanical parameters changed throughout the first five days of the experiment, until the IVDs settled into a dynamic equilibrium. In this equilibrium, degeneration was significantly related to a decrease in disc height loss during the daytime high load phase (ρ = -0.49), and to a decrease in the rate of this deformation during the final half hour of each day (ρ = -0.53). These properties were related to the nucleus glycosaminoglycan/hydroxyproline (GAG/HYP) ratio, rather than GAG content alone, indicating that remodelling of the extracellular matrix reduces poroelastic properties of the IVD. This implies that the degenerated discs have a reduced capacity to bind water and/or a reduced resistance against fluid flow. The resulting loss in hydrostatic pressure may further change cell behaviour in the nucleus pulposus.

Study Design: A biodegradable glue was biomechanically tested for annulus closure using nondegenerated goat intervertebral discs. Ultimate strength and endurance tests were performed using native and punctured discs as positive and negative controls, respectively., Objective: The aim of this study was to investigate the feasibility and biomechanical properties of a biodegradable glue for annulus closure., Summary of Background Data: There is an unmet clinical need for annulus closure techniques. Isocyanate-terminated tissue glues show potential because they adhere to annulus tissue, have an elastic modulus similar to the annulus, and show limited cytotoxicity to human annulus fibrosus cells., Methods: Three biomechanical tests were performed divided in 2 parts: part 1: ultimate strength tests comparing native, punctured (2.4-mm needle), and glued caprine intervertebral discs (n = 11 per group); part 2: 10 discs per group were subjected to a 10-day ex vivo endurance test of 864,000 load cycles, followed by ultimate strength tests. Outcome parameters include the restoration of strength after puncture, reduction of herniation in the endurance test, and conservation of glue strength after endurance testing., Results: Part 1: The glue partially restored subsidence to failure and yield strength/ultimate strength ratio of intervertebral discs. Part 2: During endurance testing, 40% of punctured discs failed compared with none of the glued discs. Endurance testing did not affect glue strength, and pooling of ultimate strength tests showed that the glue restored ultimate strength, work to failure, and yield strength/ultimate strength to 79%, 75%, and 119% of native values, respectively., Conclusion: A biodegradable isocyanate-terminated glue increases the force at which nucleus protrusion occurs, and it limits herniations during endurance or ultimate strength tests. Biomechanical tests in a bioreactor provide a low-cost assessment for annulus repair strategies; however, the clinical efficacy needs to be further addressed using long-term in vivo studies., Level of Evidence: N/A.