The anterior cruciate ligament (ACL) has poor intrinsic healing capacity due to exposure to the intra-articular synovial environment of the knee. Therefore, tendon auto- or allograft reconstruction is the mainstay of treatment for a torn ACL. Following reconstruction, there is a high rate of post-traumatic osteoarthritis, likely due to alteration of joint biomechanics, which supports the clinical need to advance primary ACL repair strategies. The ACL is enclosed by a vascularized, synovial-like sheath (ACL-s), which supplies nutrients to the central core (ACL-c). The ACL-s may act as a selective barrier to solute diffusion, protecting the ACL-c from damaging synovial enzymes and/or hyaluronic acid, while allowing nutrient diffusion. Like the synovium, the ACL-s is rich with collagens and resident macrophages, thus may be susceptible to change of function following injury and inflammation. We investigated the healthy and inflammed ACL-s structure, diffusivity, and cellular profile in comparison to the ACL-c and synovium to guide the development and optimization of primary repair technologies. Diffusion and histologic assessments revealed the ACL-s functions as a semi-permeable barrier through lower solute diffusivity and unique collagen organization. RNAseq demonstrated differential expression of extracellular matrix, inflammatory, and immune-related genes across ACL-s, ACL-c, and synovium, with the ACL-s uniquely showing upregulated expression of CX3CR1 and CLDN5 suggestive of an immunologic barrier. This study establishes the potential of the ACL-s to serve an immunologic and functional barrier that protects the underlying ACL-c from the inflammatory milieu following injury, and therefore, should be recapitulated when developing primary ACL repair technologies.

Purpose:To examine lower extremity youth soccer injuries presenting to US emergency departments. Methods:Data from the National Electronic Injury Surveillance System were analyzed for soccer players ≤18 years old sustaining lower extremity injuries from January 2013 to December 2022. Patient data collected included age, sex, mechanism of injury, setting (practice vs game), diagnosis, lower extremity injury, and disposition. Raw data were used to calculate national estimates (NEs) based on the assigned statistical sample weight of each hospital. Results:A total of 503,169 lower extremity injuries were diagnosed in US emergency departments (57.2% male; 42.8% female). On average, there was a decrease in 3,124 injuries per year from 2013 to 2022 (95% confidence interval, -5,324 to -925; P = .01) and 2,384 per year from 2013 to 2022 excluding 2020 (95% confidence interval, -3,452 to -1,315; P < .01). The ankle (NE = 196,592; 39.1%), knee (NE = 147,364; 29.3%), and foot (NE = 58,999; 11.7%) were the most commonly injured. The most common mechanisms of injury were not specified (NE = 188,653; 37.5%), ankle roll (NE = 71,992; 14.3%), and player-to-ground (NE = 581,90; 11.6%). The three most common diagnoses were strain/sprain (NE = 247,274; 49.1%), other/not stated (NE = 91,355; 18.2%), and contusion/abrasion (NE = 74,552; 14.8%). Conclusions:Youth lower extremity soccer injuries presenting to US emergency departments decreased from 2013 to 2022. Sex-specific analyses showed that there were significant differences in proportions of injuries between male and female participants for mechanism, diagnoses, and body parts injured. Clinical Relevance:This study provides insight into the epidemiology of lower extremity youth soccer injuries presenting to US emergency departments over a 10-year period.

Background:Athletes regularly face physical and psychological adversities that test their resilience. Consequently, resilience may play a significant role in shaping athletes' performance and overall well-being. Therefore, resilience's influence on crucial outcomes within sports medicine, such as injury rates, recovery processes, and performance metrics, has sparked significant discussion and investigation. Purpose:To evaluate current literature on athletes' resilience and its effects on injury incidence, recovery, and athletic performance. Study Design:Systematic review, Level of evidence, 3. Methods:A systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. This review utilized the PubMed, Embase, and Cochrane Library databases for literature search. The search was performed in December 2023 and initially identified 1387 studies. Relevant studies were selected based on defined inclusion and exclusion criteria, with data extraction focused on study characteristics, patient demographics, and key outcomes related to resilience. Due to heterogeneity in study design and outcome measures, qualitative analysis was performed rather than formal statistical analysis. Results:A total of 13 studies were included, consisting of 9 cross-sectional studies and 4 cohort studies. A total of 4400 athletes were included in these studies. A qualitative synthesis of the findings highlights resilience's significant positive impact on recovery and performance. Across the studies, high resilience was associated with better psychological well-being during recovery, reduced severity and incidence of post-concussion symptoms, and improved athletic performance. However, the effect of resilience on injury incidence was inconclusive, with studies showing varied results across different sports. Conclusion:This systematic review supports resilience as a crucial element in athletes' recovery and performance, suggesting that resilience training should be integral to rehabilitation and athlete development programs. Future research should focus on implementing resilience training in athletic settings to evaluate its effects on injury incidence, recovery, and performance metrics. The evidence supports the potential of such interventions to enhance athletes' overall well-being and sporting success.

ObjectivesNearly 3 million children participate in youth soccer annually in the United States. Popularity of youth soccer within recent years has prompted investigation describing youth-soccer concussion trends presenting to United States emergency departments (EDs). MethodsData from National Electronic Injury Surveillance System were analyzed for soccer players 2-18 years old sustaining concussions from January 2013 to December 2022. Patient data included age, sex, mechanism of injury, setting (practice vs. game), diagnosis, loss of consciousness, and disposition. Raw data were used to calculate national estimates based on assigned statistical sample weight of each hospital. ResultsA total of 80,582 youth soccer concussions were diagnosed in US EDs (51.0% female, 49.0% male). The most common mechanism of injury was head to ball (31.0%). On average, overall concussions decreased by 572 per year (p = 0.02). Head to body concussions decreased by 169 per year (p < 0.01) and head to ground concussions decreased by 155 per year (p < 0.01). No changes per year in concussion trends for head to ball, head to head, not specified, and other mechanisms. Exclusion of years 2020 and 2021 (COVID), demonstrated decreases in concussions for head to body by 125 (p = 0.01) and head to ground mechanisms by 135 per year (p = 0.01). ConclusionThere is a decreasing trend in youth soccer head injuries and concussions presenting to US emergency departments from 2013 to 2022. The trends from this study indicate that heading may be the most important aspect of soccer-related concussions presenting to US emergency departments. This study contributes to the growing literature regarding concussions in youth soccer athletes.

Rotator cuff injuries result in more than 500,000 surgeries annually in the United States, many of which fail. These surgeries typically involve repair of the injured tendon and removal of the subacromial bursa, a synovial-like tissue that sits between the rotator cuff and the acromion. The subacromial bursa has been implicated in rotator cuff pathogenesis and healing. Using proteomic profiling of bursa samples from nine patients with rotator cuff injury, we show that the bursa responds to injury in the underlying tendon. In a rat model of supraspinatus tenotomy, we evaluated the bursa’s effect on the injured supraspinatus tendon, the uninjured infraspinatus tendon, and the underlying humeral head. The bursa protected the intact infraspinatus tendon adjacent to the injured supraspinatus tendon by maintaining its mechanical properties and protected the underlying humeral head by maintaining bone morphometry. The bursa promoted an inflammatory response in injured rat tendon, initiating expression of genes associated with wound healing, including Cox2 and Il6 . These results were confirmed in rat bursa organ cultures. To evaluate the potential of the bursa as a therapeutic target, polymer microspheres loaded with dexamethasone were delivered to the intact bursae of rats after tenotomy. Dexamethasone released from the bursa reduced Il1b expression in injured rat supraspinatus tendon, suggesting that the bursa could be used for drug delivery to reduce inflammation in the healing tendon. Our findings indicate that the subacromial bursa contributes to healing in underlying tissues of the shoulder joint, suggesting that its removal during rotator cuff surgery should be reconsidered.

Background: Bunionette deformity (BD) is a painful condition of the fifth metatarsal characterized by an osseous prominence and fifth toe varus deformity. The purpose of this study is to assess the clinical, functional, and radiographic outcomes of percutaneous distal metatarsal metaphyseal osteotomy (DMMO) without fixation or postoperative strapping of the foot.Methods: A retrospective case series was performed on 111 patients (132 feet) with symptomatic BD who underwent percutaneous DMMO of the fifth metatarsal from September 2020 to January 2022 by an experienced minimally invasive surgeon. According to the Shimobayashi classification, we treated 1 type I deformity, 37 type II deformities, 52 type III deformities, 42 feet with type IV deformity, and no patient with a type V deformity. Ninety patients (81%) underwent unilateral osteotomy, and 21 (19%) had bilateral osteotomies. Most cases included other procedures including treatment of 114 associated deformities of the same feet: 68 bunions, 12 lesser metatarsal osteotomies (2-3-4 metatarsals), and 34 hammertoes (20 second hammertoes, 10 third hammertoes, 1 fourth hammertoes, 2 fifth hammertoes). Patient-reported clinical outcome measures, including the Foot Function Index (FFI) questionnaire, the visual analog score (VAS), and overall satisfaction were collected. Fourth-to-fifth intermetatarsal angle (IMA) correction, time to bone union, and complication rates were assessed in all patients.Results: Mean follow-up was 24.1 months (range, 14-39 months). Both radiographic parameters and patient-reported outcome measures significantly improved after DMMO procedure. The average fourth-to-fifth IMA improved from 12.2 degrees, preoperatively, to 4.4 degrees, postoperatively (P < .001). Patient outcomes reflect the overall outcomes of the combined surgeries on a per-patient basis. Preoperatively, patients had a mean VAS score of 7.6, which improved to 0.6 at the last follow-up (P < .001). Furthermore, the average FFI significantly decreased from pre- to postoperation from 19.2 to 4.4, respectively (P < .001). Overall, 108 of 111 patients reported being satisfied with the outcomes of the procedure. Average bone union was achieved at 12.6 weeks postoperation, with a minimum of 12 and a maximum of 25 weeks. The complication rate was 1.5%, including 1 case of an asymptomatic cock-up deformity and 1 case of lateral fifth metatarsal shaft bone overhang pain, which resolved with an exostectomy.Conclusion: The results of this study of patients who had minimally invasive surgery from an experienced surgeon suggest that percutaneous DMMO of the fifth metatarsal without internal fixation or postoperative immobilization or strapping can be effective at improving radiographic alignment, pain, function, and overall satisfaction with minimal rates of complication.Level of Evidence: Level IV, case series.

Background: Intraoperative fracture of the lateral cortex is common during Akin osteotomy. In a recent study, lateral cortex fracture did not impede healing or result in loss of correction in a combined cohort of open and percutaneous osteotomies stabilized by K-wire fixation. We hypothesize that undesired lateral cortex fracture will not affect radiographic correction and patient-reported outcomes in a percutaneous cohort stabilized by permanent, rigid screw fixation. Methods: Consecutive patients with hallux valgus who underwent first metatarsal osteotomy and percutaneous Akin osteotomy stabilized by permanent, rigid screw fixation between May 2020 and January 2022 were retrospectively reviewed. Patients were stratified based on fractured lateral cortex (FC) or its absence (nonfractured cortex [NFC]). Visual analog scale (VAS) and Foot Function Index (FFI) were used to assess pain and patient-reported outcomes at 1-year follow-up. Patients were polled for satisfaction at 1-year follow-up by yes/no survey. Results: Ninety-eight patients (89% female) were reviewed (98 feet; 43 NFC, 55 FC). Mean age was 48.3 years (range, 18-83 years). Mean preoperative VAS score was 7.5 and 7.7 in NFC and FC groups, which significantly decreased to 0.6 (P < .01) and 0.6 (P < .01), respectively. Mean total FFI was 53.9 and 54.2 and decreased to 17.9 (P < .01) and 17.2 (P < .01) in the NFC group and FC group, respectively. Overall, 97.8% of the NFC group and 96.4% of the FC group reported satisfaction. Mean HVA improved from 27.2 (16-42) degrees to 10.7 degrees (4-12) postoperatively in the NFC group. And in the FC group, HVA improved from 29.3 (19-39) degrees to 7.1 (4-12) degrees postoperatively. Postoperative HVA was significantly lower in the FC group (P < .05). Conclusion: In an exclusively percutaneous surgical cohort with correction maintained by rigid screw fixation, fracture of the lateral cortex is associated with improved postoperative radiologic alignment without detriment to patient-reported outcomes. Level of Evidence: Level III, retrospective cohort study.

Is there a formula for a competitive NIH grant application? The Serenity Prayer may provide one: "Grant me the serenity to accept the things I cannot change, the ability to change the things I can, and the wisdom to know the difference." But how to tell ...

Cells interpret cues from and interact with fibrous microenvironments through the body based on the mechanics and organization of these environments and the phenotypic state of the cell. This in turn regulates mechanoactive pathways, such as the localization of mechanosensitive factors. Here, we leverage the microscale heterogeneity inherent to engineered fiber microenvironments to produce a large morphologic data set, across multiple cells types, while simultaneously measuring mechanobiological response (YAP/TAZ nuclear localization) at the single cell level. This dataset describing a large dynamic range of cell morphologies and responses was coupled with a machine learning approach to predict the mechanobiological state of individual cells from multiple lineages. We also noted that certain cells (e.g., invasive cancer cells) or biochemical perturbations (e.g., modulating contractility) can limit the predictability of cells in a universal context. Leveraging this finding, we developed further models that incorporate biochemical cues for single cell prediction or identify individual cells that do not follow the established rules. The models developed here provide a tool for connecting cell morphology and signaling, incorporating biochemical cues in predictive models, and identifying aberrant cell behavior at the single cell level.

125 each scaffold at a density of 3,333 cells/mm. MSC-seeded scaffolds were cultured in either basal or osteogenic media (n54 per group) for 5 weeks. At the end of the culture duration, construct viability (MTT assay) and alkaline phosphatase activity (ALP, Sigma Aldrich kit) were quantified. Additional samples (n53 per group) were cryosectioned in the sagittal plane and stained for calcium deposits using a Von Kossa staining kit (Abcam).

Back and neck pain have become primary reasons for disability and healthcare spending globally. While the causes of back pain are multifactorial, intervertebral disc degeneration is frequently cited as a primary source of pain. The annulus fibrosus (AF) and nucleus pulposus (NP) subcomponents of the disc are common targets for regenerative therapeutics. However, disc degeneration is also associated with degenerative changes to adjacent spinal tissues, and successful regenerative therapies will likely need to consider and address the pathology of adjacent spinal structures beyond solely the disc subcomponents. This review summarises the current state of knowledge in the field regarding associations between back pain, disc degeneration, and degeneration of the cartilaginous and bony endplates, the AF-vertebral body interface, the facet joints and spinal muscles, in addition to a discussion of regenerative strategies for treating pain and degeneration from a whole motion segment perspective.

Background The rabbit lumbar spine is a commonly utilized model for studying intervertebral disc degeneration and for the pre-clinical evaluation of regenerative therapies. Histopathology is the foundation for which alterations to disc morphology and cellularity with degeneration, or following repair or treatment are assessed. Despite this, no standardized histology grading scale has yet been established for the spine field for any of the frequently utilized animal models. Aims The purpose of this study was to establish a new standardized scoring system to assess disc degeneration and regeneration in the rabbit model. Materials and Methods The scoring system was formulated following a review of the literature and a survey of spine researchers. Validation of the scoring system was carried out using images provided by 4 independent laboratories, which were graded by 12 independent graders of varying experience levels. Reliability testing was performed via the computation of intra-class correlation coefficients (ICC) for each category and the total score. The scoring system was then further refined based on the results of the ICC analysis and discussions amongst the authors. Results The final general scoring system involves scoring 7 features (nucleus pulposus shape, area, cellularity and matrix condensation, annulus fibrosus/nucleus pulposus border appearance, annulus fibrosus morphology, and endplate sclerosis/thickening) on a 0 (healthy) to 2 (severe degeneration) scale. ICCs demonstrated overall moderate to good agreement across graders. An addendum to the main scoring system is also included for use in studies evaluating regenerative therapeutics, which involves scoring cell cloning and morphology within the nucleus pulposus and inner annulus fibrosus. Discussion Overall, this new scoring system provides an avenue to improve standardization, allow a more accurate comparison between labs and more robust evaluation of pathophysiology and regenerative treatments across the field. Conclusion This study developed a histopathology scoring system for degeneration and regeneration in the rabbit model based on reported practice in the literature, a survey of spine researchers, and validation testing.

The intervertebral disc is the largest avascular structure in the body, and cells within the disc rely on diffusive transport via vasculature located within the vertebral endplate to receive nutrients, eliminate waste products, and maintain disc health. However, the mechanisms by which small molecule transport into the disc occurs in vivo and how these parameters change with disc degeneration remain understudied. Here, we utilize an in vivo rabbit puncture disc degeneration model to study these interactions and provide evidence that remodeling of the endplate adjacent to the disc occurs concomitant with degeneration. Our results identify significant increases in endplate bone volume fraction, increases in microscale stiffness of the soft tissue interfaces between the disc and vertebral bone, and reductions in endplate vascularity and small molecule transport into the disc as a function of degenerative state. A neural network model identified changes in diffusion into the disc as the most significant predictor of disc degeneration. These findings support the critical role of trans-endplate transport in disease progression and will improve patient selection to direct appropriate surgical intervention and inform new therapeutic approaches to improve disc health. © 2020 American Society for Bone and Mineral Research. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.

Many diseases have no visual cues in the early stages, eluding image-based detection. Today, osteoarthritis (OA) is detected after bone damage has occurred, at an irreversible stage of the disease. Currently no reliable method exists for OA detection at a reversible stage. We present an approach that enables sensitive OA detection in presymptomatic individuals. Our approach combines optimal mass transport theory with statistical pattern recognition. Eighty-six healthy individuals were selected from the Osteoarthritis Initiative, with no symptoms or visual signs of disease on imaging. On 3-y follow-up, a subset of these individuals had progressed to symptomatic OA. We trained a classifier to differentiate progressors and nonprogressors on baseline cartilage texture maps, which achieved a robust test accuracy of 78% in detecting future symptomatic OA progression 3 y prior to symptoms. This work demonstrates that OA detection may be possible at a potentially reversible stage. A key contribution of our work is direct visualization of the cartilage phenotype defining predictive ability as our technique is generative. We observe early biochemical patterns of fissuring in cartilage that define future onset of OA. In the future, coupling presymptomatic OA detection with emergent clinical therapies could modify the outcome of a disease that costs the United States healthcare system $16.5 billion annually. Furthermore, our technique is broadly applicable to earlier image-based detection of many diseases currently diagnosed at advanced stages today.

Intervertebral disc (IVD) degeneration and associated back pain place a significant burden on the population. IVD degeneration is a progressive cascade of cellular, compositional, and structural changes, which results in a loss of disc height, disorganization of extracellular matrix architecture, tears in the annulus fibrosus which may involve herniation of the nucleus pulposus, and remodeling of the bony and cartilaginous endplates (CEP). These changes to the IVD often occur concomitantly, across the entire motion segment from the disc subcomponents to the CEP and vertebral bone, making it difficult to determine the causal initiating factor of degeneration. Furthermore, assessments of the subcomponents of the IVD have been largely qualitative, with most studies focusing on a single attribute, rather than multiple adjacent IVD substructures. The objective of this study was to perform a multiscale and multimodal analysis of human lumbar motion segments across various length scales and degrees of degeneration. We performed multiple assays on every sample and identified several correlations between structural and functional measurements of disc subcomponents. Our results demonstrate that with increasing Pfirrmann grade there is a reduction in disc height and nucleus pulposus T2 relaxation time, in addition to alterations in motion segment macromechanical function, disc matrix composition and cellular morphology. At the cartilage endplate‐vertebral bone interface, substantial remodeling was observed coinciding with alterations in micromechanical properties. Finally, we report significant relationships between vertebral bone and nucleus pulposus metrics, as well as between micromechanical properties of the endplate and whole motion segment biomechanical parameters, indicating the importance of studying IVD degeneration as a whole organ.

Tissue-engineered whole disc replacements are an emerging treatment strategy for advanced intervertebral disc degeneration. A challenge facing the translation of tissue-engineered disc replacement to clinical use are the opposing needs of initial immobilization to advantage integration contrasted with physiologic loading and its anabolic effects. Here, we utilize our established rat tail model of tissue engineered disc replacement with external fixation to study the effects of remobilization at two time points postimplantation on engineered disc structure, composition, and function. Our results suggest that the restoration of mechanical loading following immobilization enhanced collagen and proteoglycan content within the nucleus pulposus and annulus fibrosus of the engineered discs, in addition to improving the integration of the endplate region of the construct with native bone. Despite these benefits, angulation of the vertebral bodies at the implanted level occurred following remobilization at both early and late time points, reducing tensile failure properties in the remobilized groups compared to the fixed group. These results demonstrate the necessity of restoring physiologic mechanical loading to engineered disc implants in vivo, and the need to transition toward their evaluation in larger animal models with more human-like anatomy and motion compared to the rat tail.

Tissue-engineered replacement discs are an area of intense investigation for the treatment of end-stage intervertebral disc (IVD) degeneration. These living implants can integrate into the disc space and recapitulate native motion segment function. We recently developed a multiphasic tissue-engineered disc-like angle-ply structure (DAPS) that models the micro-architectural and functional features of native tissue. While these implants resulted in functional restoration of the motion segment in rat and caprine models, we also noted deficiencies in cell infiltration and homogeneity of matrix deposition in the electrospun poly(e-caprolactone) outer region (annulus fibrosus, AF) of the DAPS. To address this limitation, here, we incorporated a sacrificial water-soluble polymer, polyethylene oxide (PEO), as a second fiber fraction within the AF region to increase porosity of the implant. Maturation of these PEO-modified DAPS were evaluated after 5 and 10 weeks of in vitro culture in terms of AF biochemical content, MRI T2 values, overall construct mechanical properties, AF micromechanical properties and cell and matrix distribution. To assess the performance of the PEO-modified DAPS in vivo, precultured constructs were implanted into the rat caudal disc space for 10 weeks. Results showed that matrix distribution was more homogenous in PCL/PEO DAPS, as evidenced by more robust histological staining, organized collagen deposition and micromechanical properties, compared to standard PCL-only DAPS, both in vitro and in vivo. These PCL/PEO DAPS also better approximated native micro- and macro-mechanical properties than the PCL-only DAPS, following 10 weeks of in vivo implantation. These findings demonstrate that the inclusion of a sacrificial PEO fiber fraction in the DAPS AF region improves cellular colonization, matrix elaboration, and in vitro and in vivo function of an engineered disc implant.

In fibrous tissues, prestressed boundary constraints at bone interfaces instil residual strain throughout the tissue, even when unloaded. For example, internal swelling pressures in the central nucleus pulposus of the intervertebral disc generate prestrain in the outer annulus fibrosus. With injury and depressurization, these residual strains are lost. Here we show that the loss of residual strains in the intervertebral disc alters the microenvironment and instigates aberrant tissue remodelling and the adoption of atypical cellular phenotypes. By using puncture surgery of the annulus fibrosus in rabbits, ex vivo puncture experiments and electrospun nanofibrous scaffolds recapitulating these evolving boundary constraints, we show that the loss of residual strain promotes short-term apoptosis and the emergence of a fibrotic phenotype. We also show that local fibre organization and cellular contractility mediate this process and that the aberrant cellular changes could be abrogated by targeting the cell-mechanosensing machinery with small molecules. Our findings indicate that injury to dense connective tissues under prestrain alters boundary constraints and residual strain; this leads to aberrant mechanosensing, which in turn promotes disease progression.

Objectives: The objective of this study was to perform a quantitative analysis of the structural and functional alterations in the intervertebral disc during in vivo degeneration, using emerging tools that enable rigorous assessment from the microscale to the macroscale, as well as to correlate these outcomes with noninvasive, clinically relevant imaging parameters. Design: Degeneration was induced in a rabbit model by puncturing the annulus fibrosus (AF) with a 16-gauge needle. 2, 4, 8, and 12 weeks following puncture, degenerative changes in the discs were evaluated via magnetic resonance imaging (MRI), whole motion segment biomechanics, atomic force microscopy, histology and polarized light microscopy, immunohistochemistry, biochemical content, and second harmonic generation imaging. Results: Following puncture, degeneration was evident through marked changes in whole disc structure and mechanics. Puncture acutely compromised disc macro and microscale mechanics, followed by progressive stiffening and remodeling. Histological analysis showed substantial anterior fibrotic remodeling and osteophyte formation, as well as an overall reduction in disc height, and disorganization and infolding of the AF lamellae into the NP space. Increases in NP collagen content and aggrecan breakdown products were also noted within 4 weeks. On MRI, NP T2 was reduced at all post-puncture time points and correlated significantly with microscale indentation modulus. Conclusion: This study defined the time dependent changes in disc structure-function relationships during IVD degeneration in a rabbit annular injury model and correlated degeneration severity with clinical imaging parameters. Our findings identified AF infolding and occupancy of the space as a principle mechanism of disc degeneration in response to needle puncture, and provide new insights to direct the development of novel therapeutics. (C) 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

where the applied compressive stress was equivalent to that in the human cervical discs due to the weight of the head (0 to 25 N, 0.084 MPa). eDAPS implanted motion segments were then fixed, decalcified and processed through paraffin for histology. Histologic analyses were conducted on samples from the 4 and 8-week groups. Sections were stained with alcian blue (proteoglycans) and picrosirius red (collagens). Second harmonic generation imaging (SHG) was also utilized to visualize organized collagen at the eDAPS-vertebral body interface. Significant differences (p0.05) in quantitative outcomes were assessed via Kruskal-Wallis with a Dunn’s multiple comparison test.