Biomechanical And Histological Evaluation Of Hydrogel Implants In Articular Cartilage.

We evaluated the mechanical behavior of the repaired surfaces of defective articular cartilage in the intercondylar region of the rat femur after a hydrogel graft implant. The results were compared to those for the adjacent normal articular cartilage and for control surfaces where the defects remained empty. Hydrogel synthesized by blending poly(2-hydroxyethyl methacrylate) and poly(methyl methacrylate-co-acrylic acid) was implanted in male Wistar rats. The animals were divided into five groups with postoperative follow-up periods of 3, 5, 8, 12 and 16 weeks. Indentation tests were performed on the neoformed surfaces in the knee joint (with or without a hydrogel implant) and on adjacent articular cartilage in order to assess the mechanical properties of the newly formed surface. Kruskal-Wallis analysis indicated that the mechanical behavior of the neoformed surfaces was significantly different from that of normal cartilage. Histological analysis of the repaired defects showed that the hydrogel implant filled the defect with no signs of inflammation as it was well anchored to the surrounding tissues, resulting in a newly formed articular surface. In the case of empty control defects, osseous tissue grew inside the defects and fibrous tissue formed on the articular surface of the defects. The repaired surface of the hydrogel implant was more compliant than normal articular cartilage throughout the 16 weeks following the operation, whereas the fibrous tissue that formed postoperatively over the empty defect was stiffer than normal articular cartilage after 5 weeks. This stiffness started to decrease 16 weeks after the operation, probably due to tissue degeneration. Thus, from the biomechanical and histological point of view, the hydrogel implant improved the articular surface repair.33307-1

Polyvinyl Alcohol Hydrogel Irradiated and Acetalized for Osteochondral Defect Repair: Mechanical, Chemical, and Histological Evaluation after Implantation in Rat Knees

Polyvinyl Alcohol (PVA) hydrogel plugs were implanted in artificial osteochondral defects on the trochlear groove of rat knees. After 0, 3, 6, 12, and 24 weeks of followup, samples containing the implants were mechanically evaluated by creep indentation test, chemically, and histologically by optical microscopy. The mechanical test pointed towards an increase of the implant creep modulus and the chemical analysis exhibited an increasing concentration of calcium and phosphorus within the implants over time. Optical microscopy showed no foreign body reaction and revealed formation, differentiation, and maintenance of new tissue at the defect/implant interface. The absence of implant wear indicated that the natural articular lubrication process was not disturbed by the implant. The performance of the irradiated and acetalized PVA was considered satisfactory for the proposed application

Genetic variants associated with longitudinal changes in brain structure across the lifespan

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n similar to 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Tribological properties of polyvinyl alcohol hydrogels as artificial articular cartilage

An exhaustive scientific investigation has been performed on polymeric hydrogels as potential materials to be used in cartilage tissue repair or replacement. Polyvinyl alcohol (PVA) possesses excellent properties as biocompatibility, low coefficient of friction, low interfacial tension and high permeability to fluids, emerging as an eligible material to be studied for biomedical applications. The main goal of this study was the tribological characterization of PVA hydrogels in lubricated sliding with distilled water and phosphate buffered saline solution (PBS). The influence of hydrogels mechanical properties and operating conditions were considered. Tribological tests were performed on a pin-on-plate tribometer with a linear reciprocating geometry using the PVA/stainless steel 316L and PVA/bovine articular cartilage pairs. Experiments were performed at 37 °C with a constant reciprocating sliding frequency of 1 Hz and applied load of 1 MPa, 2 MPa and 3.5 MPa. For each experiment the friction coefficient was determined and the dominating wear mechanisms analysed by scanning electron microscopy and EDS. PVA showed an excellent performance as possible material for the repair of articular cartilage due to the high level of surface preservation and the very low friction coefficient presented when PBS was used as fluid lubricant. The performed tribological study revealed the high potentiality of PVA hydrogels to be used as artificial articular cartilage.(undefined

Polyvinyl Alcohol Hydrogel Irradiated And Acetalized For Osteochondral Defect Repair: Mechanical, Chemical, And Histological Evaluation After Implantation In Rat Knees.

Polyvinyl Alcohol (PVA) hydrogel plugs were implanted in artificial osteochondral defects on the trochlear groove of rat knees. After 0, 3, 6, 12, and 24 weeks of followup, samples containing the implants were mechanically evaluated by creep indentation test, chemically, and histologically by optical microscopy. The mechanical test pointed towards an increase of the implant creep modulus and the chemical analysis exhibited an increasing concentration of calcium and phosphorus within the implants over time. Optical microscopy showed no foreign body reaction and revealed formation, differentiation, and maintenance of new tissue at the defect/implant interface. The absence of implant wear indicated that the natural articular lubrication process was not disturbed by the implant. The performance of the irradiated and acetalized PVA was considered satisfactory for the proposed application.201258268

Tribological characterization of polyvinyl alcohol hydrogel as substitute of articular cartilage

Polyvinyl alcohol (PVA) hydrogels are considered as promising biomaterials to substitute damaged articular cartilage due to their excellent biocompatibility, high permeability to fluids and low friction coefficient against smooth and wet surfaces. The study aims to demonstrate that under tribological loading mimicking in vivo conditions, PVA hydrogel/natural articular cartilage consists in a particular combination of mating surfaces with friction and wear characteristics compatible with the application as articular joints. Hydrogel membranes having approximately 1 mm thickness were processed from PVA aqueous solutions (Aldrich Mw 89000–98000 g/mol, 99% hydrolized), with 10% (w/w) concentration of polymer in solution, to be used as tribological samples against bovine articular cartilage. In order to ensure the natural properties and resistance of the tissue, articular cartilage samples were collected from condyles and prepared with 4 mm subchondral bone. Tribological tests were performed on a pin-on-plate tribometer with a linear reciprocating geometry in the presence of distilled water and phosphate buffered saline solution (PBS) at 37 ºC. The reciprocating sliding frequency and stroke length were kept constant at 1 Hz and 8 mm, respectively. Contact pressures ranging from 1 MPa to 5 MPa were applied. For each experiment the friction coefficient was determined and the dominant wear mechanisms analysed by SEM. The topography of hydrogel membranes in the hydrated state was evaluated with AFM microscopy for quantitative and qualitative analysis of worn surfaces. Results show that PVA hydrogel present excellent tribological performance against natural articular cartilage with very low friction coefficient values (~0.02 to 0.05) combined with the preservation of both mating surfaces

Randomized controlled trial comparing hyaluronic acid, platelet-rich plasma and the combination of both in the treatment of mild and moderate osteoarthritis of the knee

Objective: This study aims to evaluate the clinical effects of Platelet Rich Plasma (PRP) and Hyaluronic Acid (HA) as individual treatments for mild to moderate Osteoarthritis (OA), and also examine the potential synergistic effects of PRP in combination with HA. Research continues to emerge examining the potential therapeutic efficacy of HA and PRP as autologous injectable treatments for joint arthritis. However, there is a paucity of research investigating the effects of combining HA and PRP on pain and functional status in patients with OA. Design: In this multicenter, randomized, controlled, double blind, prospective trial, 105 patients with mild to moderate knee osteoarthritis who met the study criteria were randomly allocated to one of three interventions: HA (n=36), PRP (n=36), or HA+PRP (n=33). Each patient received 3 intaarticular knee injections of their assigned substance, with 2 week intervals between each injection. Clinical outcomes were evaluated using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Visual Analogue Scale (VAS) questionnaire at baseline and after 1,3,6, and 12 months. Results: The study showed that the PRP group have significant reduction in VAS scores at 1 (p= 0.003), 3 (p= 0.0001), 6 (p= 0.0001) and 12 (p= 0.000) months when compared to HA. In addition, the PRP group illustrated greater improvement in WOMAC physical activity scale at 12 months (p= 0.008) when compared to the HA group. Combining HA and PRP resulted in a significant decreases in pain (p=0.0001) and functional limitation (p=0.0001) when compared to HA alone at 1 year post treatment; and significantly increased physical function at 1 (p=0.0004) and 3 (p=.011) months when compared to PRP alone. Conclusion: The findings of the study support the use of autologous PRP as an effective treatment of mild to moderate knee osteoarthritis. It also shows that the combination of HA and PRP resulted to better outcomes than HA alone up to 1 year and PRP alone up to 3 months. Furthermore, the results suggest that combination of PRP and HA could potentially provide better functional outcomes in the first 30 days after treatment with both PRP and HA alone122P69P78sem informaçãosem informaçã