The MEDITAGING study: protocol of a two-armed randomized controlled study to compare the effects of the mindfulness-based stress reduction program against a health promotion program in older migrants in Luxembourg.

BACKGROUND: Migration is a phenomenon worldwide, with older migrants, particularly those with fewer socioeconomic resources, having an increased risk of developing adverse cognitive and health outcomes and social isolation. Therefore, it is of utmost importance to validate interventions that promote healthy aging in this population. Previous studies have shown a positive impact of mindfulness based-stress reduction (MBSR) on outcomes such as cognition and sleep. However, only a few studies verified its potential in older adults, especially with vulnerable populations such as migrants. This article presents the protocol of the MEDITAGING study, which is the first to investigate the MBSR effects in migrants aged ≥55 in comparison to a health promotion program. METHODS: MEDITAGING is a two-arm randomized, double-blinded, controlled study, which will include older Portuguese-speaking migrants (n = 90). Participants are randomized to the MBSR or a health promotion program. Both interventions are conducted in groups over a total of 8 weeks, incorporating weekly meetings, an additional 4-hour class, and extra at-home tasks. The health promotion program has the same structure as the MBSR but comprises different activities related to dementia prevention, healthy habits, cognitive stimulation, sleeping, nutrition, watercolor painting, and physical activity. The assessment of executive functioning, physiological stress measures, self-reported questionnaires, and qualitative interviews are conducted at baseline, after 8 weeks (post-intervention), and at a follow-up session (from one to 3 months thereafter). Analyzes will be conducted using a modified intention-to-treat approach (all participants with at least 3 days of participation in the group-sessions and one post-intervention observation). DISCUSSION: This study will test effects of a mindfulness-based intervention against an active control condition in older adult migrants, which few studies have addressed. TRIAL REGISTRATION: ClinicalTrials.gov NCT05615337 (date of registration: 27 September 2022; date of record verification: 14 November 2022).

A leucine-rich repeat kinase 2 (LRRK2) pathway biomarker characterization study in patients with Parkinson's disease with and without LRRK2 mutations and healthy controls.

Increased leucine-rich repeat kinase 2 (LRRK2) kinase activity is an established risk factor for Parkinson's disease (PD), and several LRRK2 kinase inhibitors are in clinical development as potential novel disease-modifying therapeutics. This biomarker characterization study explored within- and between-subject variability of multiple LRRK2 pathway biomarkers (total LRRK2 [tLRRK2], phosphorylation of the serine 935 (Ser935) residue on LRRK2 [pS935], phosphorylation of Rab10 [pRab10], and total Rab10 [tRab10]) in different biological sources (whole blood, peripheral blood mononuclear cells [PBMCs], neutrophils) as candidate human target engagement and pharmacodynamic biomarkers for implementation in phase I/II pharmacological studies of LRRK2 inhibitors. PD patients with a LRRK2 mutation (n = 6), idiopathic PD patients (n = 6), and healthy matched control subjects (n = 10) were recruited for repeated blood and cerebrospinal fluid (CSF) sampling split over 2 days. Within-subject variability (geometric coefficient of variation [CV], %) of these biomarkers was lowest in whole blood and neutrophils (range: 12.64%-51.32%) and considerably higher in PBMCs (range: 34.81%-273.88%). Between-subject variability displayed a similar pattern, with relatively lower variability in neutrophils (range: 61.30%-66.26%) and whole blood (range: 44.94%-123.11%), and considerably higher variability in PBMCs (range: 189.60%-415.19%). Group-level differences were observed with elevated mean pRab10 levels in neutrophils and a reduced mean pS935/tLRRK2 ratio in PBMCs in PD LRRK2-mutation carriers compared to healthy controls. These findings suggest that the evaluated biomarkers and assays could be used to verify pharmacological mechanisms of action and help explore the dose-response of LRRK2 inhibitors in early-phase clinical studies. In addition, comparable α-synuclein aggregation in CSF was observed in LRRK2-mutation carriers compared to idiopathic PD patients.

Identification of peripheral vascular function measures and circulating biomarkers of mitochondrial function in patients with mitochondrial disease.

The development of pharmacological therapies for mitochondrial diseases is hampered by the lack of tissue-level and circulating biomarkers reflecting effects of compounds on endothelial and mitochondrial function. This phase 0 study aimed to identify biomarkers differentiating between patients with mitochondrial disease and healthy volunteers (HVs). In this cross-sectional case-control study, eight participants with mitochondrial disease and eight HVs matched on age, sex, and body mass index underwent study assessments consisting of blood collection for evaluation of plasma and serum biomarkers, mitochondrial function in peripheral blood mononuclear cells (PBMCs), and an array of imaging methods for assessment of (micro)circulation. Plasma biomarkers GDF-15, IL-6, NT-proBNP, and cTNI were significantly elevated in patients compared to HVs, as were several clinical chemistry and hematology markers. No differences between groups were found for mitochondrial membrane potential, mitochondrial reactive oxygen production, oxygen consumption rate, or extracellular acidification rate in PBMCs. Imaging revealed significantly higher nicotinamide-adenine-dinucleotide-hydrogen (NADH) content in skin as well as reduced passive leg movement-induced hyperemia in patients. This study confirmed results of earlier studies regarding plasma biomarkers in mitochondrial disease and identified several imaging techniques that could detect functional differences at the tissue level between participants with mitochondrial disease and HVs. However, assays of mitochondrial function in PBMCs did not show differences between participants with mitochondrial disease and HVs, possibly reflecting compensatory mechanisms and heterogeneity in mutational load. In future clinical trials, using a mix of imaging and blood-based biomarkers may be advisable, as well as combining these with an in vivo challenge to disturb homeostasis.

A Biomarker Study in Patients with GBA1-Parkinson's Disease and Healthy Controls.

BACKGROUND: Molecules related to glucocerebrosidase (GCase) are potential biomarkers for development of compounds targeting GBA1-associated Parkinson's disease (GBA-PD). OBJECTIVES: Assessing variability of various glycosphingolipids (GSLs) in plasma, peripheral blood mononuclear cells (PBMCs), and cerebrospinal fluid (CSF) across GBA-PD, idiopathic PD (iPD), and healthy volunteers (HVs). METHODS: Data from five studies were combined. Variability was assessed of glucosylceramide (various isoforms), lactosylceramide (various isoforms), glucosylsphingosine, galactosylsphingosine, GCase activity (using fluorescent 4-methylumbeliferryl-ß-glucoside), and GCase protein (using enzyme-linked immunosorbent assay) in plasma, PBMCs, and CSF if available, in GBA-PD, iPD, and HVs. GSLs in leukocyte subtypes were compared in HVs. Principal component analysis was used to explore global patterns in GSLs, clinical characteristics (Movement Disorder Society - Unified Parkinson's Disease Rating Scale Part 3 [MDS-UPDRS-3], Mini-Mental State Examination [MMSE], GBA1 mutation type), and participant status (GBA-PD, iPD, HVs). RESULTS: Within-subject between-day variability ranged from 5.8% to 44.5% and was generally lower in plasma than in PBMCs. Extracellular glucosylceramide levels (plasma) were slightly higher in GBA-PD compared with both iPD and HVs, while intracellular levels were comparable. GSLs in the different matrices (plasma, PBMCs, CSF) did not correlate. Both lactosylceramide and glucosylsphingosine were more abundant in granulocytes compared with monocytes and lymphocytes. Absolute levels of GSL isoforms differed greatly. GBA1 mutation types could not be differentiated based on GSL data. CONCLUSIONS: Glucosylceramide can stably be measured over days in both plasma and PBMCs and may be used as a biomarker in clinical trials targeting GBA-PD. Glucosylsphingosine and lactosylceramide are stable in plasma but are strongly affected by leukocyte subtypes in PBMCs. GBA-PD could be differentiated from iPD and HVs, primarily based on glucosylceramide levels in plasma. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Examining the effects of emotional valence and arousal on source memory: A meta-analysis of behavioral evidence.

The current meta-analysis examined the effects of valence and arousal on source memory accuracy, including the identification of variables that moderate the magnitude and direction of those effects. Fifty-three studies, comprising 85 individual experiments (N = 3,040 participants), were selected. Three separate analyses focusing on valence effects (valence-based: negative-neutral; positive-neutral; negative-positive) and other three focusing exclusively on arousal (arousal-based: high-low; medium-low; high-medium) were considered. Effect sizes varied from very small to medium. For the valence-based analyses, source memory accuracy was impaired for emotional compared with neutral stimuli (dunb = -.14 for negative-neutral; dunb = -.11 for positive-neutral), with a similar performance found for the negative-positive comparison (dunb = -.04). In the case of arousal-based analyses, source memory was improved for stimuli with high and medium arousal versus low arousal (dunb = .27, dunb = .49, respectively), with no statistically significant difference between high and medium arousal stimuli (dunb = -.12). Emotion effects on source memory were modulated by methodological factors. These factors may account for the variety findings typically found in emotion-related source memory research and could be systematically addressed in future studies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Corrigendum: Processing speed mediates the association between physical activity and executive functioning in elderly adults.

[This corrects the article DOI: 10.3389/fpsyg.2022.958535.].

Processing speed mediates the association between physical activity and executive functioning in elderly adults.

Advanced aging is associated with cognitive decline. To decrease the healthcare system and socio-economic burdens as well as to promote better quality of life, is important to uncover the factors that may be related to the delay of cognitive impairments in older adults. This study investigated the relationship between physical activity levels, sedentary behavior and cardiorespiratory fitness with cognitive functioning in healthy older adults. Furthermore, it examined the mediating role of processing speed on the association between physical activity and executive functions and long-term memory. Thirty-two individuals aged between 63 and 77 years (M = 68.16, SD = 3.73) underwent measurements of maximal oxygen uptake (VO2peak), 1-week of PA accelerometer measurement and a comprehensive cognitive assessment. Significant associations were observed between MVPA and cognitive processing speed. Equally, a significant positive indirect effect of MVPA on executive functioning and long-term memory was mediated by processing speed. Also, MVPA levels differentiated cognitive functioning in older adults - the physical active group outperformed the physical inactive group in processing speed, executive functions, and language abilities. Our results contribute to the literature on the MVPA levels as an important tool to promote healthier cognitive aging.

Working Memory Training Coupled With Transcranial Direct Current Stimulation in Older Adults: A Randomized Controlled Experiment.

Background: Transcranial direct current stimulation (tDCS) has been employed to boost working memory training (WMT) effects. Nevertheless, there is limited evidence on the efficacy of this combination in older adults. The present study is aimed to assess the delayed transfer effects of tDCS coupled with WMT in older adults in a 15-day follow-up. We explored if general cognitive ability, age, and educational level predicted the effects. Methods: In this single-center, double-blind randomized sham-controlled experiment, 54 older adults were randomized into three groups: anodal-tDCS (atDCS)+WMT, sham-tDCS (stDCS)+WMT, and double-sham. Five sessions of tDCS (2 mA) were applied over the left dorsolateral prefrontal cortex (DLPFC). Far transfer was measured by Raven's Advanced Progressive Matrices (RAPM), while the near transfer effects were assessed through Digit Span. A frequentist linear mixed model (LMM) was complemented by a Bayesian approach in data analysis. Results: Working memory training improved dual n-back performance in both groups submitted to this intervention but only the group that received atDCS+WMT displayed a significant improvement from pretest to follow-up in transfer measures of reasoning (RAPM) and short-term memory (forward Digit Span). Near transfer improvements predicted gains in far transfer, demonstrating that the far transfer is due to an improvement in the trained construct of working memory. Age, formal education, and vocabulary score seem to predict the gains in reasoning. However, Bayesian results do not provide substantial evidence to support this claim. Conclusion: This study will help to consolidate the incipient but auspicious field of cognitive training coupled with tDCS in healthy older adults. Our findings demonstrated that atDCS may potentialize WMT by promoting transfer effects in short-term memory and reasoning in older adults, which are observed especially at follow-up.

Macromolecular modulation of a 3D hydrogel construct differentially regulates human stem cell tissue-to-tissue interface.

The simultaneous generation of multiple tissues and their functional assembly into complex tissues remains a critical challenge for regenerative medicine. The tissue-to-tissue interface connecting two adjacent tissues is vital in effective tissue function. The presented worked hypothesize that differential functional property can be engineered by modulating the macromolecular composition of a 3D hydrogel construct and distinctively endow stem cell fate. Hence, it was possible to successfully generate macromolecular constructs by using the extracellular matrix (ECM)-based materials; type I collagen (Col I) and hyaluronic acid (HA); and natural-derived biomaterials as methacrylated gellan-gum (GGMA). The 3D hydrogel constructs consisted of two dissimilar layers: 1) Col I: HA hydrogel and 2) GGMA hydrogel. The tissue-to-tissue interface was created by seeding human mesenchymal stem cells (MSCs) between the two layers. Differential functional rheological and mechanical properties characterized the acellular 3D gradient hydrogel constructs. The cell-based 3D hydrogel constructs were assessed for MSCs viability by live/dead staining. Assessing apoptosis by flow cytometry, data showed the feasibility of the 3D hydrogel constructs in maintaining cell viability with no apoptosis induction onto MSCs. A homogeneous distribution was achieved in a successful cellular tissue-to-tissue interface. Human MSCs low proliferative rate and low ECM deposition were seen for all constructs; however, lower proliferative rate within the ECM microenvironment highlights controlled self-renewal of MSCs. The 3D hydrogel constructs maintained the human MSCs phenotype, yet the macromolecular modulation allowed tuning the human MSCs morphology from round to spindle-shaped phenotype. The intrinsic properties of the 3D cell-based hydrogel construct induced differential inflammatory and angiogenic paracrine secretory profiles owing to the dissimilar engineered biophysical milieu. Human MSCs sense the nearby macromolecular environment adjusting the cell-ECM interactions, which influence cell behaviour and fate. Beyond multi-tissue regeneration, the engineered cellular 3D hydrogel constructs may simultaneously address immune regeneration.

The modulatory role of internet-supported mindfulness-based cognitive therapy on extracellular vesicles and psychological distress in people who have had cancer: a protocol for a two-armed randomized controlled study.

BACKGROUND: Mindfulness-based interventions (MBIs) have been used in oncology contexts as a promising tool with numerous benefits for various health-related and psychosocial outcomes. Despite the increasing popularity of MBIs, few randomized controlled trials (RCTs) have examined their effects upon biological parameters. Specifically, no previous study has examined the effects of MBIs on extracellular vesicles (EVs), which are potentially important markers of health, disease, and stress. Moreover, the lack of RCTs is even more limited within the context of technology-mediated MBIs and long-term effects. METHODS: The current study protocol presents a two-arm, parallel, randomized controlled study investigating the effects of internet-supported mindfulness-based cognitive therapy (MBCT) compared with treatment as usual (TAU). Primary outcomes are psychological distress and EV cargo of distressed participants with previous breast, colorectal, or prostate cancer diagnoses. Secondary outcomes are self-reported psychosocial and health-related measures, and additional biological markers. Outcomes will be assessed at baseline, 4 weeks after baseline (mid-point of the intervention), 8 weeks after baseline (immediately post-intervention), 24 weeks after baseline (after booster sessions), and 52 weeks after baseline. Our goal is to recruit at least 111 participants who have been diagnosed with breast, prostate, or colorectal cancer (cancer stage I to III), are between 18 and 65 years old, and have had primary cancer treatments completed between 3 months and 5 years ago. Half of the participants will be randomized to the TAU group, and the other half will participate in an 8-week online MBCT intervention with weekly group sessions via videoconference. The intervention also includes asynchronous homework, an online retreat after the fifth week, and 4 monthly booster sessions after completion of the 8-week programme. DISCUSSION: This study will allow characterizing the effects of internet-based MBCT on psychosocial and biological indicators in the context of cancer. The effects on circulating EVs will also be investigated, as a possible neurobiological pathway underlying mind-body intervention effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT04727593 (date of registration: 27 January 2021; date of record verification: 6 October 2021).

Interactions of Emotion and Self-reference in Source Memory: An ERP Study.

The way emotional information is encoded (e.g., deciding whether it is self-related or not) has been found to affect source memory. However, few studies have addressed how the emotional quality and self-referential properties of a stimulus interactively modulate brain responses during stimulus encoding and source memory recognition. In the current study, 22 participants completed five study-test cycles with negative, neutral, and positive words encoded in self-referential versus non-self-referential conditions, while event-related potentials of the electroencephalogram were recorded. An advantage of self-referential processing in source memory performance, reflected in increased recognition accuracy, was shown for neutral and positive words. At the electrophysiological level, self-referential words elicited increased amplitudes in later processing stages during encoding (700-1,200 ms) and were associated with the emergence of old/new effects in the 300-500 ms latency window linked to familiarity effects. In the 500-800 ms latency window, old/new effects emerged for all valence conditions except for negative words studied in the non-self-referential condition. Negative self-referential words also elicited a greater mobilization of post-retrieval monitoring processes, reflected in an enhanced mean amplitude in the 800-1,200 ms latency window. Together, the current findings suggest that valence and self-reference interactively modulate source memory. Specifically, negative self-related information is more likely to interfere with the recollection of source memory features.

Is internal source memory recognition modulated by emotional encoding contexts?

The influence of emotion on memory has been mainly examined by manipulating the emotional valence and/or arousal of critical items. Few studies probed how emotional information presented during the encoding of critical neutral items modulates memory recognition, particularly when considering source memory features. In this study, we specified the role of emotional encoding contexts in internal source memory performance (discrimination between encoding tasks) using a mixed (Experiment 1) and a blocked design (Experiment 2). During the study phase, participants were required to evaluate a set of neutral words, using either a self-referential or a semantic (common judgment) encoding strategy. Prior and concomitantly with each word, negative, neutral or positive pictures were presented in the background. The beneficial effect of self-referential encoding was observed for both item and internal source memory in both experiments. Remarkably, item and internal source memory recognition was not modulated by emotion, even though a secondary analysis indicated that the consistent exposure to negative (vs. positive) information led to worse source memory performance. These findings suggest that internal source memory of neutral items is not always affected by changing or repetitive emotional encoding contexts.

How Does Performing Demanding Activities Influence Prospective Memory? A Systematic Review.

This paper is the first systematic review on the role of ongoing task load in prospective remembering, which was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Forty articles published between 1995 and 2020 were included. They evaluated prospective memory (PM) performance (i.e., the ability to remember to execute a delayed intention) in adult samples aged between 19 and 50 years old when the PM cue appeared under cognitively demanding conditions. The results revealed that people are more likely to fail to remember to perform a delayed intention at the appropriate circumstances or time in the future when their cognitive resources are taxed by demanding ongoing activities. We conclude the review by highlighting that the degree of working memory and executive resources seems to account for some of the discrepant findings and by proposing directions for future research.

Probing the relationship between late endogenous ERP components with fluid intelligence in healthy older adults.

The world population is rapidly aging, bringing together the necessity to better understand the advancing age. This characterization may be used to aid early diagnosis and to guide individually-tailored interventions. While some event-related potential (ERP) components, such as the P300 and late positive complex (LPC), have been associated with fluid intelligence (Gf) in young population; little is known whether these associations hold for older people. Therefore, the main goal of this study was to assess whether these ERP components are associated with Gf in the elderly. Fifty-seven older adults performed a continuous performance task (CPT) and a visual oddball paradigm while EEG was recorded. Participants were divided into two groups, according to their performance in the Raven's Advanced Progressive Matrices test: high-performance (HP) and low-performance (LP). Results showed that the HP group, compared to the LP group, had higher LPC amplitudes in the CPT and shorter P300 latencies in the oddball task, highlighting the role of ERP components as a potential electrophysiological proxy of Gf abilities in the elderly.

Differential Effects of Valence and Encoding Strategy on Internal Source Memory and Judgments of Source: Exploring the Production and the Self-Reference Effect.

Item memory studies show that emotional stimuli are associated with improved memory performance compared to neutral ones. However, emotion-related effects on source memory are less consistent. The current study probed how emotional valence and specific encoding conditions influence internal source memory performance and judgments of source (JOSs). In two independent experiments, participants were required to read silently/aloud (Experiment 1) or to perform self-reference/common judgments (Experiment 2) on a list of negative/neutral/positive words. They also performed immediate JOSs ratings for each word. The study phase was followed by a test phase in which participants performed old-new judgments. In Experiment 1, the production effect was replicated for item memory, but the effects of valence on item and source memory were not significant. In Experiment 2, self-referential processing effects on item and source memory differed as a function of valence. In both experiments, JOSs ratings were sensitive to valence and encoding conditions, although they were not predictive of objective memory performance. These findings demonstrate that the effects of valence on internal source memory and JOSs are modulated by encoding strategy. Thus, the way information is encoded can shed light on how emotion might enhance, impair or exert no influence on source memory.

Reviewing working memory training gains in healthy older adults: A meta-analytic review of transfer for cognitive outcomes.

The objective of this meta-analytic review was to systematically assess the effects of working memory training on healthy older adults. We identified 552 entries, of which 27 experiments met our inclusion criteria. The final database included 1130 participants. Near- and far-transfer effects were analysed with measures of short-term memory, working memory, and reasoning. Small significant and long-lasting transfer gains were observed in working memory tasks. Effects on reasoning was very small and only marginally significant. The effects of working memory training on both near and far transfer in older adults were moderated by the type of training tasks; the adopted outcome measures; the training duration; and the total number of training hours. In this review, we provide an updated review of the literature in the field by carrying out a robust multi-level meta-analysis focused exclusively on working memory training in healthy older adults. Recommendations for future research are suggested.

Subjective Memory Complaints in Portuguese Young Adults: Contributions from the Adaptation of the Prospective and Retrospective Memory Questionnaire.

Self-report instruments that allow to characterize the frequency of daily memory failures are essential for a comprehensive assessment of memory functioning. In this context, we aimed to provide preliminary evidence of validity and reliability for the European Portuguese adaptation of the Prospective and Retrospective Memory Questionnaire (PRMQ). A total of 1052 healthy participants completed an online survey with the PRMQ. The exploration of the construct validity suggested the tripartite model with a general memory, a prospective memory, and a retrospective memory factors to have the best adjustment to the data. Measurement invariance across age and sex groups was also verified. The questionnaire revealed good convergent validity with a general self-report measure of memory (0.778 < r < 0.853), and satisfactory values of internal consistency (0.779 < Cronbach's alpha < 0.887) and of test-retest reliability (0.815 < r < 0.852). There were no prominent effects of sex and age in the PRMQ scores. Although the sample encompassed mainly younger and highly educated adults, this study presented the first evidence of validity and reliability for the European Portuguese version of the questionnaire.

Gellan gum-hydroxyapatite composite spongy-like hydrogels for bone tissue engineering.

Osteoinductive biomaterials represent a promising approach to advance bone grafting. Despite promising, the combination of sustained biodegradability, mechanical strength, and biocompatibility in a unique biomaterial that can also support cell performance and bone formation in vivo is demanding. Herein, we developed gellan gum (GG)-hydroxyapatite (HAp) spongy-like hydrogels to mimic the organic (GG) and inorganic (HAp) phases of the bone. HAp was successfully introduced within the GG polymeric networks, as determined by FTIR and XRD, without compromising the thermostability of the biomaterials, as showed by TGA. The developed biomaterials showed sustained degradation, high swelling, pore sizes between 200 and 300 µm, high porosity (>90%) and interconnectivity (<60%) that was inversely proportional to the total polymeric amount and to CaCl2 crosslinker. CaCl2 and HAp reinforced the mechanical properties of the biomaterials from a storage modulus of 40 KPa to 70-80 KPa. This study also showed that HAp and CaCl2 favored the bioactivity and that cells were able to adhere and spread within the biomaterials up to 21 days of culture. Overall, the possibility to tailor spongy-like hydrogels properties by including calcium as a crosslinker and by varying the amount of HAp will further contribute to understand how these features influence bone cells performance in vitro and bone formation in vivo. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 479-490, 2018.

Nanocellulose reinforced gellan-gum hydrogels as potential biological substitutes for annulus fibrosus tissue regeneration.

Intervertebral disc (IVD) degeneration is associated with both structural damage and aging related degeneration. Annulus fibrosus (AF) defects such as annular tears, herniation and discectomy require novel tissue engineering strategies to functionally repair AF tissue. An ideal construct will repair the AF by providing physical and biological support, facilitating regeneration. The presented strategy herein proposes a gellan gum-based construct reinforced with cellulose nanocrystals (nCell) as a biological self-gelling AF substitute. Nanocomposite hydrogels were fabricated and characterized with respect to hydrogel swelling capacity, degradation rate in vitro and mechanical properties. Rheological evaluation on the nanocomposites demonstrated the GGMA reinforcement with nCell promoted matrix entanglement with higher scaffold stiffness observed upon ionic crosslinking. Compressive mechanical tests demonstrated compressive modulus values close to those of the human AF tissue. Furthermore, cell culture studies with encapsulated bovine AF cells indicated that nanocomposite constructs promoted cell viability and a physiologically relevant cell morphology for up to fourteen days in vitro.