The essential anti-angiogenic strategies in cartilage engineering and osteoarthritic cartilage repair.

In the cartilage matrix, complex interactions occur between angiogenic and anti-angiogenic components, growth factors, and environmental stressors to maintain a proper cartilage phenotype that allows for effective load bearing and force distribution. However, as seen in both degenerative disease and tissue engineering, cartilage can lose its vascular resistance. This vascularization then leads to matrix breakdown, chondrocyte apoptosis, and ossification. Research has shown that articular cartilage inflammation leads to compromised joint function and decreased clinical potential for regeneration. Unfortunately, few articles comprehensively summarize what we have learned from previous investigations. In this review, we summarize our current understanding of the factors that stabilize chondrocytes to prevent terminal differentiation and applications of these factors to rescue the cartilage phenotype during cartilage engineering and osteoarthritis treatment. Inhibiting vascularization will allow for enhanced phenotypic stability so that we are able to develop more stable implants for cartilage repair and regeneration.

Functional aspects of the Eustachian tube by means of 3D-modeling.

The extent of dysfunction of the Eustachian tube (ET) is relevant in understanding the pathogenesis of secondary otological diseases such as acute or chronic otitis media. The underlying mechanism of ET dysfunction remains poorly understood except for an apparent genesis such as a nasopharyngeal tumor or cleft palate. To better describe the ET, its functional anatomy, and the biomechanical valve mechanism and subsequent development of diagnostic and interventional tools, a three-dimensional model based on thin-layer histology was created from an ET in this study. Blackface sheep was chosen as a donor. The 3-D model was generated by the coherent alignment of the sections. It was then compared with the cone-beam computed tomography dataset of the complete embedded specimen taken before slicing. The model shows the topographic relation of the individual components, such as the bone and cartilage, the muscles and connective tissue, as well as the lining epithelium with the lumen. It indicates a limited spiraling rotation of the cartilaginous tube over its length and relevant positional relationships of the tensor and levator veli palatine muscles.

Taxonomic changes in the gut microbiota are associated with cartilage damage independent of adiposity, high fat diet, and joint injury.

Lipodystrophic mice are protected from cartilage damage following joint injury. This protection can be reversed by the implantation of a small adipose tissue graft. The purpose of this study was to evaluate the relationship between the gut microbiota and knee cartilage damage while controlling for adiposity, high fat diet, and joint injury using lipodystrophic (LD) mice. LD and littermate control (WT) mice were fed a high fat diet, chow diet, or were rescued with fat implantation, then challenged with destabilization of the medial meniscus surgery to induce osteoarthritis (OA). 16S rRNA sequencing was conducted on feces. MaAslin2 was used to determine associations between taxonomic relative abundance and OA severity. While serum LPS levels between groups were similar, synovial fluid LPS levels were increased in both limbs of HFD WT mice compared to all groups, except for fat transplanted animals. The Bacteroidetes:Firmicutes ratio of the gut microbiota was significantly reduced in HFD and OA-rescued animals when compared to chow. Nine novel significant associations were found between gut microbiota taxa and OA severity. These findings suggest the presence of causal relationships the gut microbiome and cartilage health, independent of diet or adiposity, providing potential therapeutic targets through manipulation of the microbiome.

Midterm Follow-Up and Assessment of Cartilage Thickness by Arthro-Magnetic Resonance Imaging After Arthroscopic Cam Resection, Labral Repair, and Rim Trimming Without Labral Detachment.

PURPOSE: To evaluate the clinical and radiological outcome, sum of acetabular and femoral cartilage thickness, and rate of failure in the midterm after arthroscopic treatment of femoroacetabular impingement (FAI) syndrome with femoral osteoplasty, labral repair, and rim trimming without labral detachment. METHODS: This retrospective case series included patients with FAI syndrome who had undergone hip arthroscopy from January 2009 to December 2010 by a single surgeon, with a minimum follow-up of 55 months. Data from patients who had undergone arthroscopic hip procedures with labral repair, rim trimming, and femoral osteoplasty were analyzed pre- and postoperatively. Clinical outcome (nonarthritic hip score [NAHS], Short Form 36 [SF-36]), range of motion, progression of osteoarthritis (Tönnis grade), radiological parameters (α angle, lateral center-edge angle [LCEA], Tönnis angle), femoral and acetabular cartilage thickness (using magnetic resonance imaging [MRI]), and intraoperative findings were evaluated. RESULTS: Of 148 hip arthroscopies performed, 97 included rim trimming, labral refixation, and femoral osteoplasty. Ten cases were lost to follow-up, leaving 87 hips. Arthroscopic revision was performed on 4 hips and total hip replacement on 4 hips, and 1 hip underwent both arthroscopic revision and total hip replacement. Excluding these 9 cases of revision, for which follow-up was not possible (retrospective study), the remaining 78 hips were followed up for a minimum of 55 months (77 ± 11.4, mean ± SD; range 55 to 124). Mean NAHS (65 to 88, P < .001), SF-36 physical subscale (65 to 85, P < .001), and the numerical pain rating scale (NRS) (5 to 1, P < .001) improved significantly. Outcome scores of minimal clinical importance (NAHS) were achieved in 67.6% of the patients. Mean range of movement improved significantly in flexion (109 to 122, P < .001) and internal rotation (10 to 22.7, P < .001). NAHS was positively associated with flexion of the hip postoperatively (r = 0.307, P = .011). In 16 cases, microfracture was performed (15 acetabular and 1 femoral). Preoperative α angles (anteroposterior and modified Dunn) were significantly higher in this cohort (P < .001, 95% confidence interval 8.9 to 25.2, P = .001). Twenty hips (28 %) progressed to worse Tönnis grades. Initial Tönnis grades were grade 0, 38; grade 1, 48; grade 2, 8. Pre- or postoperative Tönnis grades did not show any correlation with pre- or postoperative NAHS and NRS. MRI measurements at the latest follow-up (69 patients) of the femoral and acetabular cartilage thickness did not reveal any significant reduction at the 12 o'clock position. CONCLUSION: Arthroscopic cam resection, rim trimming, and labral repair without detachment of the labrum provides good or excellent outcome in 77.1% of hips based on NAHS in the midterm. Higher range of motion in flexion is associated with higher NAHS postoperatively. Arthroscopic cam resection, rim trimming and labral repair without detachment of the labrum is a successful method for the treatment of FAI syndrome in the midterm. LEVEL OF EVIDENCE: IV, retrospective case series.

The relationship between motor performance and femoral cartilage thickness in children with Down syndrome.

Down syndrome (DS) is a genetic disorder associated with mental and motor developmental delays in childhood. The aim of this study was to investigate the relationship of the femoral cartilage thickness with motor performance in children with Down syndrome (DS). A total of 39 children with DS in the age range of 12-42 months were included in the study (female/male: 21/18; mean age: 23.4 ± 8.2 months). Femoral cartilage thickness was measured with ultrasound in the medial and lateral condyles and intercondylar areas of both knees. Gross motor subtest scaled scores of the Bayley Scales of Infant and Toddler Development III were used for the motor performance assessment. There was a positive correlation between the gross motor scaled scores and the femoral cartilage thickness in both knee joints (p < .05; r = 0.415 for the right medial condyle; r = 0.323 for the right lateral condyle; r = 0.339 for the right intercondylar area; r = 0.369 for the left medial condyle; r = 0.364 for the left lateral condyle, and r = 0.590 for the left intercondylar area). The study demonstrated that the femoral cartilage thickness was positively correlated with gross motor functioning in children with DS.

T2 mapping of the acetabular cartilage in infants and children with developmental dysplasia of the hip.

BACKGROUND: T2 mapping is useful for evaluating the cartilage matrix. PURPOSE: To determine the variations in the acetabular cartilage T2 relaxation values between healthy individuals and those with developmental dysplasia of the hip (DDH). MATERIAL AND METHODS: Thirty-three patients with unilateral DDH underwent 3-T magnetic resonance imaging (MRI) between January 2018 and February 2019. Fifteen volunteers (30 hips) were enrolled as controls. T2 values were measured with the T2 mapping sequence in all layers and were equally divided into three layers (deep, middle, and superficial) with equal thickness. We calculated the mean T2 relaxation values for the full thickness, deep, middle, and superficial layers and compared the values between the different groups. In addition, the inter- and intra-observer agreements were calculated. RESULTS: The T2 relaxation values in the DDH arm were significantly lower in the middle, superficial, and full thickness layers compared with those of the volunteers and contralateral hips. The T2 relaxation values of the deep layers showed no significant difference between the different groups. The acetabular cartilage T2 relaxation values increased from the deep layer to the superficial layer in the control and contralateral groups. Both inter- and intra-observer agreements were good. CONCLUSION: MRI T2 mapping may help to diagnose developmental disorders of the acetabular cartilage matrix in infants and children with DDH. Abnormal acetabular cartilage T2 relaxation values may be due to the extraordinary stress load of the femoral head.

Mesenchymal stem cell-derived small extracellular vesicles and bone regeneration.

Mesenchymal stem cells (MSCs) and MSC-derived small extracellular vesicles (sEVs) are promising candidates for cell-based and cell-free regenerative medicine, respectively. By virtue of their multiple lineage differentiation capacity, MSCs have been implicated as an ideal tool for bone and cartilage regeneration. However, later observations attributed such regenerative effects to MSC-secreted paracrine factors. Exosomes, endosomal originated sEVs carrying lipid, protein and nucleic acid cargoes, were identified as components of the MSC secretome and propagated the key regenerative and immunoregulatory characteristics of parental MSCs. Here, exosome biogenesis, the molecular composition of exosomes, sEV-cell interactions and the effects on key bone homeostasis cells are reviewed. MSC-derived sEVs show to promote neovascularization and bone and cartilage regeneration in preclinical disease models. The mechanisms include the transfer of molecules, including microRNAs, mRNAs and proteins, to other key cells. MSC-derived sEVs are interesting candidates as biopharmaceuticals for drug delivery and for the engineering of biologically functionalized materials. Although major exploratory efforts have been made for therapeutic development, the secretion, distribution and biological effects of MSC-derived sEVs in bone and cartilage regeneration are not fully understood. Moreover, techniques for high-yield production, purity and storage need to be optimized before effective and safe MSC-derived sEVs therapies are realized.

Impact of Chronic Lateral Ankle Instability with Lateral Collateral Ligament Injuries on Biochemical Alterations in the Cartilage of the Subtalar and Midtarsal Joints Based on MRI T2 Mapping.

OBJECTIVE: To quantitatively assess biochemical alterations in the cartilage of the subtalar and midtarsal joints in chronic lateral ankle instability (CLAI) patients with isolated anterior talofibular ligament (ATFL) injuries and combined calcaneofibular ligament (CFL) injuries using MRI T2 mapping. MATERIALS AND METHODS: This study was performed according to regulations of the Committee for Human Research at our institution, and written informed consent was obtained from all participants. Forty CLAI patients (26 with isolated ATFL injuries and 14 with combined ATFL and CFL injuries) and 25 healthy subjects were recruited for this study. All participants underwent MRI scans with T2 mapping. Patients were assessed with the American Orthopedic Foot and Ankle Society (AOFAS) rating system. The subtalar and midtarsal joints were segmented into 14 cartilage subregions. The T2 value of each subregion was measured from T2 mapping images. Data were analyzed with ANOVA, the Student's t test, and Pearson's correlation coefficient. RESULTS: T2 values of most subregions of the subtalar joint and the calcaneal facet of the calcaneocuboid joint in CLAI patients with combined CFL injuries were higher than those in healthy controls (all p < 0.05). However, there were no significant differences in T2 values in subtalar and midtarsal joints between patients with isolated ATFL injuries and healthy controls (all p > 0.05). Moreover, T2 values of the medial talar subregions of the posterior subtalar joint in patients with combined CFL injuries showed negative correlations with the AOFAS scores (r = -0.687, p = 0.007; r = -0.609, p = 0.021, respectively). CONCLUSION: CLAI with combined CFL injuries can lead to cartilage degeneration in subtalar and calcaneocuboid joints, while an isolated ATFL injury might not have a significant impact on the cartilage in these joints.

Novel Insights Into the Role of N6-Methyladenosine RNA Modification in Bone Pathophysiology.

Thus far, there are more than known 150 modifications to RNA, in which common internal modifications of mRNA include N6-methyladenosine (m6A), N1-methyladenosine, and 5-methylcytosine. Among them, m6A RNA modification is one of the highest abundance modifications in eukaryotes, regulating mechanisms controlling gene expression at the post-transcription level. As an invertible and dynamic epigenetic marker, m6A base modification influences almost all vital biological processes, cellular components, and molecular functions. Once the m6A modification process is abnormal, a series of diseases-including cancer, neurological diseases, and growth disorders-will be caused. Besides, several base modification activities also have been created by noncoding RNAs (ncRNAs), for instance, microRNAs, and circular RNAs, long ncRNAs, which were dynamically regulated during bone and cartilage pathophysiology processes. Therefore, it has now been clear that dynamic modification on coding RNAs and ncRNAs represents a completely new way to modulate genetic information. In this review, we highlight up-to-date progress and applications of m6A RNA modification in bone and cartilage pathophysiology, and we discuss the pathological roles and underlying molecular mechanism of m6A modifications in osteoarthritis and osteoporosis and osteosarcoma pathogenesis.

Evaluation of nucleus pulposus fluid velocity and pressure alteration induced by cartilage endplate sclerosis using a poro-elastic finite element analysis.

The nucleus pulposus (NP) in the intervertebral disk (IVD) depends on diffusive fluid transport for nutrients through the cartilage endplate (CEP). Disruption in fluid exchange of the NP is considered a cause of IVD degeneration. Furthermore, CEP calcification and sclerosis are hypothesized to restrict fluid flow between the NP and CEP by decreasing permeability and porosity of the CEP matrix. We performed a finite element analysis of an L3-L4 lumbar functional spine unit with poro-elastic constitutive equations. The aim of the study was to predict changes in the solid and fluid parameters of the IVD and CEP under structural changes in CEP. A compressive load of 500 N was applied followed by a 10 Nm moment in extension, flexion, lateral bending, and axial rotation to the L3-L4 model with fully saturated IVD, CEP, and cancellous bone. A healthy case of L3-L4 physiology was then compared to two cases of CEP sclerosis: a calcified cartilage endplate and a fluid constricted sclerotic cartilage endplate. Predicted NP fluid velocity increased for the calcified CEP and decreased for the calcified + less permeable CEP. Decreased NP fluid velocity was prominent in the axial direction through the CEP due to a less permeable path available for fluid flux. Fluid pressure and maximum principal stress in the NP were predicted to increase in both cases of CEP sclerosis compared to the healthy case. The porous medium predictions of this analysis agree with the hypothesis that CEP sclerosis decreases fluid flow out of the NP, builds up fluid pressure in the NP, and increases the stress concentrations in the NP solid matrix.

Cartilage Homeostasis Affects Femoral Head Necrosis Induced by Methylprednisolone in Broilers.

(1) Background: Since the large-scale poultry industry has been established, femoral head necrosis (FHN) has always been a major leg disease in fast-growing broilers worldwide. Previous research suggested that cartilage homeostasis could be taken into consideration in the cause of FHN, but the evidence is insufficient. (2) Methods: One-day-old broiler chickens were randomly divided into three groups, 16 broilers per group. The birds in group L were injected intramuscularly with methylprednisolone (MP) twice a week for four weeks (12.5 mg·kg-1). The birds in group H were injected intramuscularly with MP (20 mg·kg-1·d-1) for 7 d (impulse treatment). The birds in group C were treated with sterile saline as a control group. Broilers were sacrificed at 42 and 56 d. Blood samples were collected from the jugular vein for ELISA and biochemical analysis. Bone samples, including femur, tibia, and humerus, were collected for histopathological analysis, bone parameters detection, and real-time quantitative PCR detection. (3) Results: The FHN broilers in group L and H both showed lower body weight (BW) and reduced bone parameters. In addition, the MP treatment resulted in reduced extracellular matrix (ECM) anabolism and enhanced ECM catabolism. Meanwhile, the autophagy and apoptosis of chondrocytes were enhanced, which led to the destruction of cartilage homeostasis. Moreover, the impulse MP injection increased the portion of birds with severer FHN, whereas the MP injection over a long period caused a more evident change in serum cytokine concentrations and bone metabolism indicators. (4) Conclusions: The imbalance of cartilage homeostasis may play a critical role in the development of FHN in broilers. FHN broilers induced by MP showed a more pronounced production of catabolic factors and suppressed the anabolic factors, which might activate the genes of the WNT signal pathway and hypoxia-inducible factors (HIFs), and then upregulate the transcription expression of ECM to restore homeostasis.

Jumonji domain containing-3 (JMJD3) inhibition attenuates IL-1ß-induced chondrocytes damage in vitro and protects osteoarthritis cartilage in vivo.

OBJECTIVES: This study aimed to explore the effects and relative mechanism of JMJD3 on knee osteoarthritis (OA). METHODS: In this study, we first analyzed the expression of JMJD3 in OA cartilage using western blot and immunohistochemistry. In an in vitro study, the effects of GSK-J4, JMJD3 inhibitor, on ATDC-5 chondrocytes were evaluated by CCK-8 assay. Real-time PCR and western blot were used to examine the inhibitory effect of GSK-J4 on the inflammation and ECM degradation of chondrocytes. NF-κB p65 phosphorylation and nuclear translocation were measured by western blot and immunofluorescence. In the animal study, twenty mice were randomized into four experimental groups: sham group, DMM-induced OA + DMSO group, OA + low-dose GSK-J4 group, and OA + high-dose GSK-J4 group. After the treatment, hematoxylin-eosin and safranin O/fast green staining were used to evaluate cartilage degradation of knee joint, with OARSI scores for quantitative assessment of cartilage damage. RESULTS: Our results revealed that JMJD3 was overexpressed in OA cartilage and GSK-J4 could suppress the IL-1ß-induced production of pro-inflammatory cytokines and catabolic enzymes, including IL-6, IL-8, MMP-9 and ADAMTS-5. Consistent with these findings, GSK-J4 could inhibit IL-1ß-induced degradation of collagen II and aggrecan. Mechanistically, GSK-J4 dramatically suppressed IL-1ß-stimulated NF-κB signal pathway activation. In vivo, GSK-J4 prevented cartilage damage in mouse DMM-induced OA model. CONCLUSIONS: This study elucidates the important role of JMJD3 in cartilage degeneration in OA, and our results indicate that JDJM3 may become a novel therapeutic target in OA therapy.

Distal tuberosity osteotomy in open-wedge high tibial osteotomy does not exacerbate patellofemoral osteoarthritis on arthroscopic evaluation.

PURPOSE: The purpose of the present study was to use arthroscopy to evaluate the effect of distal tuberosity osteotomy (DTO) in open-wedge high tibial osteotomy (OW-HTO) on patellofemoral (PF) cartilage degradation. METHODS: Between 2012 and 2017, 46 knees underwent DTO in OW-HTO, and 65 knees underwent conventional OW-HTO (cOW-HTO). To assess changes in patellar height, the Blackburne-Peel (BP) ratio and the Caton-Deschamps (CD) index were measured. Arthroscopic evaluation on the PF joint was performed at the initial osteotomy and at the second-look procedure 1 year later. Statistical analyses were performed to compare difference between the DTO and the cOW-HTO group. RESULTS: In the cOW-HTO group, the mean BP ratio and CD index decreased significantly from 0.81 and 0.89 preoperatively, respectively, to 0.69 and 0.76 postoperatively, respectively (p < 0.001). In contrast, the DTO group maintained a consistent patellar height; the mean BP ratio and CD index were 0.77 and 0.83 preoperatively, respectively, and 0.73 and 0.80 postoperatively, respectively. Upon arthroscopic evaluation, 39 of 46 patients (84.8%) in the DTO group showed no progression of PF cartilage degradation at the second look; indeed, five of 46 patients (10.9%) even demonstrated improvement. In contrast, 21 of 65 patients (32.3%) in the cOW-HTO group exhibited increased PF cartilage degradation. There was a significant difference in progression of PF cartilage degradation between DTO and cOW-HTO (p < 0.001). CONCLUSION: DTO in OW-HTO maintained the preoperative patellar height, which could help prevent progression of cartilage degeneration in the PF joint after surgery. In respect of the biplanar osteotomy direction in OW-HTO, the DTO, rather than cOWHTO, is the preferred technique for the treatment of varus knee osteoarthritis to avoid progression of PF cartilage degradation. LEVEL OF EVIDENCE: III.

Short term outcomes of hip arthroscopy on hip joint mechanics and cartilage health in patients with femoroacetabular impingement syndrome.

BACKGROUND: Femoroacetabular acetabular impingement syndrome consists of abnormal hip joint morphology resulting in painful hip joint impingement. Hip arthroscopy corrects the abnormal morphology and reduces clinical symptoms associated with femoroacetabular impingement syndrome yet the effects of hip arthroscopy on gait mechanics and cartilage health are not well understood. METHODS: Ten femoroacetabular impingement syndrome patients and 10 matched asymptomatic controls underwent gait analysis consisting of three-dimensional hip joint kinematics and kinetics. Femoroacetabular impingement syndrome patients underwent gait analysis and quantitative magnetic resonance imaging of the surgical hip joint before and seven months post-surgery. Patient reported outcomes were obtained from all study participants and were used to quantify hip joint pain, function and quality of life. FINDINGS: Prior to surgery, femoroacetabular impingement syndrome patients demonstrated hip joint kinematics or kinetics as the control group. After surgery, femoroacetabular impingement syndrome patients exhibited improved patient reported outcomes, similar hip joint kinematic patterns, increased hip flexion and decreased hip extension moment impulses within the surgical limb. The femoroacetabular impingement syndrome patients that ambulated with increased HFMI post-surgery demonstrated a decrease in femoral cartilage T1ρ and T2 values. INTERPRETATION: Femoroacetabular impingement syndrome patients exhibited improved clinical symptoms yet ambulated with altered sagittal plane hip joint loading after hip arthroscopy. Increased hip flexion moment impulse post-surgery was associated with improved cartilage health within the surgical limb. These study findings suggest that sagittal plane hip joint loading at short-term follow-up after hip arthroscopy is associated with cartilage health and may be an important biomechanical parameter in post-operative rehabilitation programs.

ADAMTS4 and ADAMTS5 may be considered as new molecular therapeutic targets for cartilage damages with Kashin-Beck Disease.

There are a pretty number of research demonstrating that ADAMTS4 and ADAMTS5 playing primary roles in the degradation of cartilage during inflammatory joint diseases like osteoarthritis (OA). Because Kashin-Beck Disease (KBD) has been found to own the common pathological changes and symptoms with OA, and is regarded as the specific type of osteoarthritis, it's reasonable to believe that ADAMTS4 and ADAMTS5 may exert an enormous functions on the injury of cartilage of the KBD and may be potential molecular therapeutic targets for KBD.

Association of glucose homeostasis and metabolic syndrome with knee cartilage defects and cartilage volume in young adults.

OBJECTIVE: To describe the associations of glucose homeostasis and metabolic syndrome (MetS) measures with knee cartilage defects and cartilage volume in young adults. METHODS: Fasting blood biochemistry, waist circumference and blood pressure measures were collected 4-5 years prior to knee magnetic resonance imaging (MRI) scans. Blood measures included levels of glucose, insulin, triglyceride and high-density lipoprotein cholesterol (HDL-C). Homeostatic model assessment 2-insulin resistance (HOMA2-IR), HOMA2-beta cell function (HOMA2-ß), HOMA2-insulin sensitivity (HOMA-S) and MetS were calculated or defined. Knee cartilage defects and cartilage volume were measured from MRI scans. Data were analysed using log binomial or linear regressions. RESULTS: Among 328 participants (47.3% were females, aged 26-36 years at baseline), 40 (12.7%) had hyperglycaemia and 21 (6.7%) had MetS. Glucose homeostasis measures (except fasting glucose) were associated with tibiofemoral cartilage defects (fasting insulin: relative risk (RR) 1.05, 95% confidence interval (CI) 1.01 to 1.08; HOMA2-IR: 1.44, 1.08 to 1.92; HOMA2-ß: 2.59, 1.33 to 5.07; HOMA2-S: 0.36, 0.18 to 0.72), but not patellar cartilage defects. There were no associations between glucose homeostasis measures and knee cartilage volume. High waist circumference (RR 2.32, 95% CI 1.18 to 4.54) and low HDL-C (RR 1.99, 95% CI 1.08 to 3.69) were associated with tibiofemoral cartilage defects, but no other associations were observed between MetS or its components and cartilage defects or volume. CONCLUSION: Insulin resistance, high waist circumference and low HDL-C were associated with higher risk of tibiofemoral cartilage defects, suggesting glucose homeostasis and some MetS components may affect early cartilage damage in young adults.

Viewpoint on the role of tissue maintenance in ageing: focus on biomarkers of bone, cartilage, muscle, and brain tissue maintenance.

Specific hallmarks are thought to underlie the ageing process and age-related functional decline. In this viewpoint, we put forward the hypothesis that disturbances in the process of tissue maintenance are an important common denominator that may lie in between specific hallmarks of ageing (i.e. damage and responses to damage) and their ultimate (patho)physiological consequences (i.e. functional decline and age-related disease). As a first step towards verifying or falsifying this hypothesis, it will be important to measure biomarkers of tissue maintenance in future studies in different study populations. The main aim of the current paper is to discuss potential biomarkers of tissue maintenance that could be used in such future studies. Among the many tissues that could have been chosen to explore our hypothesis, to keep the paper manageable, we chose to focus on a selected number of tissues, namely bone, cartilage, muscle, and the brain, which are important for mobility and cognition and affected in several common age-related diseases, including osteoporosis, osteoarthritis, sarcopenia, and neurodegenerative diseases. Furthermore, we discuss the advantages and limitations of potential biomarkers for use in (pre)clinical studies. The proposed biomarkers should be validated in future research, for example by measuring these in humans with different rates of ageing.

High-strength cellulose-polyacrylamide hydrogels: Mechanical behavior and structure depending on the type of cellulose.

Two types of stiff and high-strength composite hydrogels possessing the structure of interpenetrating polymer networks were synthesized via free-radical polymerization of acrylamide carried out straight within the previously formed physical network of regenerated plant cellulose or bacterial cellulose (PC and BC respectively) that was swollen in the reactive solution. The mechanical behavior of synthesized hydrogels subjected to the action of compressive deformations with different amplitude values was studied. The analysis of the stress-strain curves of compression tests of the hydrogels of both types obtained in different test conditions demonstrates the substantial difference in their mechanical behavior. Both the PC- and BC-based hydrogels withstand successfully the one-shot compression with the amplitude up to 80%, but in the conditions of the multiple compression tests (cyclic compressions) during the subsequent compression acts the dramatic increase in the stiffness of the BC-based hydrogels was observed at the deformation region beyond 60%. This effect can be explained by the deep reorganization of the intermolecular structure of the material with the stress-induced reorientation of BC micro-fibrils. Submicron- and micron-scale specific features of structures of composite hydrogels of both types were studied by cryo-scanning electron microscopy to explain the peculiarities of the mechanical effects observed.

Tibiotalar cartilage stress corresponds to T2 mapping: application to barefoot running in novice and marathon-experienced runners.

A 3D anatomically-based finite-element foot model was adopted for predicting von Mises stresses within tibiotalar cartilage following 5 km barefoot running. To compare this predicted stress with T2 maps, magnetic resonance scans of the right ankle and plantar pressure were obtained from ten novices and ten marathon-experienced runners before and after running. Following running, tibiotalar cartilage stress was decreased in experienced runners. This corresponded with T2 values that did not change between pre- and post-running suggesting no increase in cartilage fluid levels. In contrast, novices maintained the same level of von Mises stress and this corresponded with a significant T2 increase in tibiotalar cartilage.

Demographic and Radiographic Factors Associated With Intra-articular Hip Cartilage Injury: A Cross-sectional Study of 1511 Hip Arthroscopy Procedures.

BACKGROUND: Moderate to severe (grade 3-4) hip joint cartilage injury seems to impair function in patients with femoroacetabular impingement syndrome. PURPOSE: To investigate whether demographic and radiographic factors were associated with moderate to severe hip joint cartilage injury. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Patients were identified in the Danish Hip Arthroscopy Registry. The outcome variables were acetabular cartilage injury (modified Beck grade 0-2 vs 3-4) and femoral head cartilage injury (International Cartilage Repair Society grade 0-2 vs 3-4). Logistic regressions assessed the association with the following: age (<30 vs 30-50 years); sex; sport activity level (Hip Sports Activity Scale); alpha angle (AA) assessed as normal (AA <55°), cam (55°≤ AA <78°), or severe cam (AA ≥78°); lateral center-edge angle (LCEA) assessed as normal (25°≤ LCEA ≤ 39°), pincer (LCEA >39°), or borderline dysplasia (LCEA <25°); joint space width (JSW) assessed as normal (JSW >4.0 mm), mild reduction (3.1 mm ≤ JSW ≤ 4.0 mm), or severe reduction (2.1 mm ≤ JSW ≤ 3.0 mm). RESULTS: A total of 1511 patients were included (mean ± SD age: 34.9 ± 9.8 years). Male sex (odds ratio [OR], 4.42), higher age (OR, 1.70), increased AA (cam: OR, 2.23; severe cam: OR, 4.82), and reduced JSW (mild: OR, 2.04; severe: OR, 3.19) were associated (P < .05) with Beck grade 3-4. Higher age (OR, 1.92), increased Hip Sports Activity Scale (OR, 1.13), borderline dysplasia (OR, 3.08), and reduced JSW (mild: OR, 2.63; severe: OR, 3.04) were associated (P < .05) with International Cartilage Repair Society grade 3-4. CONCLUSION: Several demographic and radiographic factors were associated with moderate to severe hip joint cartilage injury. Most notably, increased cam severity and borderline dysplasia substantially increased the risk of grade 3-4 acetabular and femoral head cartilage injury, respectively, indicating that specific deformity may drive specific cartilage injury patterns in the hip joint.