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The molecular connectivity and the extent of hydrogen-bond patterns of water molecules confined in the polymer hydrogels, namely, cyclodextrin nanosponge hydrogels, are here investigated by using vibrational spectroscopy experiments. The proposed spectroscopic method exploits the combined analysis of the vibrational spectra of polymers hydrated with water and deuterated water, which allows us to separate and selectively investigate the temperature-evolution of the HOH bending mode of engaged water molecules and of the vibrational modes assigned to specific chemical groups of the polymer matrix involved in the physical interactions with water. As main results, we find a strong experimental evidence of a liquid-like behaviour of water molecules confined in the nano-cavities of hydrogel and we observe a characteristic destructuring effect on the hydrogen-bonds network of confined water induced by thermal motion. More interestingly, the extent of this temperaturedisruptive effect is found to be selectively triggered by the cross-linking degree of the hydrogel matrix. These results give a more clear picture of the molecular mechanism of water confinement in the pores of nanosponge hydrogel and open the possibility to exploit the spectroscopic method here proposed as investigating tools for water-retaining soft materials. [ABSTRACT FROM AUTHOR]

UV Raman and Brillouin light scattering (BLS) experiments have been used in this study to explore the complex phase change behavior occurring in pH-responsive polysaccharide hydrogels as a function of temperature. Due to the different physical quantities measured by the two techniques, the joint analysis of Raman and BLS spectra has provided an unprecedented large-scale characterization of the molecular rearrangements and of the different kinds of hydrophilic and hydrophobic interactions that cooperate to determine the phase transformation observed in these hydrogels during the heating of the gel. As the main result, the analysis of the Raman and BLS spectra showed the existence of a correlation between the local (molecular) and collective properties of the gels during the phase transformation undergone by the system, which is markedly triggered by pH. The joint set of experimental results suggests a model according to which the mechanism of pH dependence in the hydrogels under investigation is dominated by the interactions involving the hydrophobic parts of the polymer skeleton, whereas the solvation process observed under heating of the gels is driven by the progressive distancing of the polymer domains among them, as monitored by the Brillouin sound velocity. [ABSTRACT FROM AUTHOR]

The focus of this work is on addressing how the adsorption properties of cyclodextrin (CD) based polymeric hydrogels (cyclodextrin nanosponges, CDNS) can be regulated by a precise control of a crucial parameter such as the characteristic pore size of the polymer network. With this aim, Small Angle Neutron Scattering (SANS) experiments are performed on different CDNS polymer formulations, differing by (i) the chemical structure of the cross-linking agent used for the polymerization of CD, which affects the flexibility of the strands between two crosslinking junctions, (ii) the relative molar ratio of cross-linker to monomer, affecting the cross-linking density, and (iii) the dimension of the CD macrocycle, regulating the steric hindrance and number of available reactive sites on the monomer. The analysis of the experimental data in terms of a two-correlation-length model allows one to extract a correlation length ζ that is interpreted as an experimental assessment of the average mesh-size of the cross-linked polymer, confirming the effective nano-size of the cavities formed in the network of CDNS. The hydration-dependence of ζ is modelled by an empirical functional form, that provides as key parameters the swelling rate of the polymeric network and the upper limit for the mesh size of the material. These parameters are useful for the characterization of the dynamic response of the hydrogel to swelling and the maximum mesh size compatible with the chemical structure of the polymer. [ABSTRACT FROM AUTHOR]

The fundamental question of how the reorganization of the hydrogen-bond (HB) network of water is influenced by the combination of nano-confinement and hydrophobic/hydrophilic solvation effects is addressed here using a spectroscopic study of water absorbed in a model, pH-sensitive polysaccharide hydrogel. The effects of temperature, hydration level and pH on the vibrational dynamics associated with the water molecules and the polymer skeleton are disentangled and analysed by a complementary and combined use of UV-Raman scattering and IR spectroscopy. The experimental data give evidence that the solvation effects in the hydrogel matrix are essentially dominated by the hydration of more hydrophobic parts of the polymer network, while the effect of pH on the HB reorganization of confined water molecules is found to be similar to that induced by cooling of the system. A tentative explanation of these results has been provided in terms of interplay between different kinds of interactions, i.e. hydrophobic vs. hydrophilic. [ABSTRACT FROM AUTHOR]

A detailed experimental and theoretical vibrational analysis of hydrogels of β-cyclodextrin nanosponges (β-CDNS), obtained by polymerization of β-cyclodextrin (β-CD) with the cross-linking agent ethylenediaminetetraacetic acid (EDTA), is reported here. Thorough structural characterization is achieved by exploiting the complementary selection rules of FTIR-ATR and Raman spectroscopies and by supporting the spectral assignments by DFT calculations of the spectral profiles. The combined analysis of the FTIR-ATR spectra of the polymers hydrated with H2O and D2O allowed us to isolate the HOH bending of water molecules not involved in symmetrical, tetrahedral environments. The analysis of the HOH bending mode was carried out as a function of temperature, showing the existence of a supercooled state of the water molecules. The highest level of cooperativity of the hydrogen bond scheme was reached at a value of the β-CD/EDTA molar ratio n = 6. Finally, the connectivity pattern of “uncoupled” water molecules bound to the nanosponge backbone was found to be weakened by increasing T. The temperature above which the population of non-tetracoordinated water molecules becomes predominant turned out to be independent of the parameter n. [ABSTRACT FROM AUTHOR]

The molecular dynamics of water and a polymer matrix is here explored in a paradigmatic model of a polysaccharide hydrogel, by the combined use of UV Raman scattering and infrared measurements. The case example of cyclodextrin nanosponges (CDNS)/hydrogel is chosen since the simultaneous presence in the structure of the polymer matrix of both hydrophilic and hydrophobic sites mimics the complexity of polysaccharide hydrogels. In this way, the contributions provided by the balance between the hydrophilicity/hydrophobicity and the grade of entanglement of the polymer hydrogel to lead to the formation of the gel phase are separately accounted and evaluated. As main results, we found that the hydrophobic CH groups inserted on the aromatic ring of CDNS experience a more pronounced dynamic perturbation with respect to the carbonyl groups due to the collision between the solvent and vibrating atoms of the polymer. The overall results provide a detailed molecular picture of the swelling phenomena occurring when a chemically cross-linked polymer contacts with water or biological fluids and exploits the potentiality of UV Raman spectroscopy to retrieve dynamic information besides their structural counterpart obtained by the classical analysis of the basic features of vibrational spectra. [ABSTRACT FROM AUTHOR]

Cyclodextrin nanosponges (CDNS) provide a very promising class of cross-linked polymers consisting of cyclodextrins as building blocks and showing a characteristic nanoporous structure capable of effectively encapsulating and carrying a variety of both lipophilic and hydrophilic compounds. Hereafter, we investigate the vibrational dynamics of CDNS in the low-wave number region, with the aim to provide physical descriptors correlated to the elastic properties of this innovative glass-forming material. By means of Raman scattering measurements, we explore the modifications occurring to the boson peak (BP) as a function of the cavity size of the cyclodextrin and the relative amount of the cross-linking agent with respect to the monomer cyclodextrin, which can be varied during the synthesis of the polymer. The shift and intensity variations of the BP are discussed in terms of the modification of the elastic properties of CDNS, and a master curve for the boson peak can therefore be obtained. The experimental approach adopted here is a useful tool for investigating the structural and physicochemical properties of novel nanoporous soft materials of interest for biolife applications. [ABSTRACT FROM AUTHOR]

Objectives: Pelvic organ prolapse is the descent of one or more reproductive organs from their normal position, causing associated negative symptoms. One conservative treatment option is pessary management. This study aimed to to investigate the cost-effectiveness of pessary self-management (SM) when compared with clinic-based care (CBC). A decision analytic model was developed to extend the economic evaluation., Methods: A randomized controlled trial with health economic evaluation. The SM group received a 30-minute SM teaching session, information leaflet, 2-week follow-up call, and a local helpline number. The CBC group received routine outpatient pessary appointments, determined by usual practice. The primary outcome for the cost-effectiveness analysis was incremental cost per quality-adjusted life year (QALY), 18 months post-randomization. Uncertainty was handled using nonparametric bootstrap analysis. In addition, a simple decision analytic model was developed using the trial data to extend the analysis over a 5-year period., Results: There was no significant difference in the mean number of QALYs gained between SM and CBC (1.241 vs 1.221), but mean cost was lower for SM (£578 vs £728). The incremental net benefit estimated at a willingness to pay of £20 000 per QALY gained was £564, with an 80.8% probability of cost-effectiveness. The modeling results were consistent with the trial analysis: the incremental net benefit was estimated as £4221, and the probability of SM being cost-effective at 5 years was 69.7%., Conclusions: Results suggest that pessary SM is likely to be cost-effective. The decision analytic model suggests that this result is likely to persist over longer durations., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Background: Pelvic organ prolapse is common, causes unpleasant symptoms and negatively affects women's quality of life. In the UK, most women with pelvic organ prolapse attend clinics for pessary care., Objectives: To determine the clinical effectiveness and cost-effectiveness of vaginal pessary self-management on prolapse-specific quality of life for women with prolapse compared with clinic-based care; and to assess intervention acceptability and contextual influences on effectiveness, adherence and fidelity., Design: A multicentre, parallel-group, superiority randomised controlled trial with a mixed-methods process evaluation., Participants: Women attending UK NHS outpatient pessary services, aged ≥ 18 years, using a pessary of any type/material (except shelf, Gellhorn or Cube) for at least 2 weeks. Exclusions: women with limited manual dexterity, with cognitive deficit (prohibiting consent or self-management), pregnant or non-English-speaking., Intervention: The self-management intervention involved a 30-minute teaching appointment, an information leaflet, a 2-week follow-up telephone call and a local clinic telephone helpline number. Clinic-based care involved routine appointments determined by centres' usual practice., Allocation: Remote web-based application; minimisation was by age, pessary user type and centre., Blinding: Participants, those delivering the intervention and researchers were not blinded to group allocation., Outcomes: The patient-reported primary outcome (measured using the Pelvic Floor Impact Questionnaire-7) was prolapse-specific quality of life, and the cost-effectiveness outcome was incremental cost per quality-adjusted life-year (a specifically developed health Resource Use Questionnaire was used) at 18 months post randomisation. Secondary outcome measures included self-efficacy and complications. Process evaluation data were collected by interview, audio-recording and checklist. Analysis was by intention to treat., Results: Three hundred and forty women were randomised (self-management, n = 169; clinic-based care, n = 171). At 18 months post randomisation, 291 questionnaires with valid primary outcome data were available (self-management, n = 139; clinic-based care, n = 152). Baseline economic analysis was based on 264 participants (self-management, n = 125; clinic-based care, n = 139) with valid quality of life and resource use data. Self-management was an acceptable intervention. There was no group difference in prolapse-specific quality of life at 18 months (adjusted mean difference -0.03, 95% confidence interval -9.32 to 9.25). There was fidelity to intervention delivery. Self-management was cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained, with an estimated incremental net benefit of £564.32 and an 80.81% probability of cost-effectiveness. At 18 months, more pessary complications were reported in the clinic-based care group (adjusted mean difference 3.83, 95% confidence interval 0.81 to 6.86). There was no group difference in general self-efficacy, but self-managing women were more confident in pessary self-management activities. In both groups, contextual factors impacted on adherence and effectiveness. There were no reported serious unexpected serious adverse reactions. There were 32 serious adverse events (self-management, n = 17; clinic-based care, n = 14), all unrelated to the intervention. Skew in the baseline data for the Pelvic Floor Impact Questionnaire-7, the influence of the global COVID-19 pandemic, the potential effects of crossover and the lack of ethnic diversity in the recruited sample were possible limitations., Conclusions: Self-management was acceptable and cost-effective, led to fewer complications and did not improve or worsen quality of life for women with prolapse compared with clinic-based care. Future research is needed to develop a quality-of-life measure that is sensitive to the changes women desire from treatment., Study Registration: This study is registered as ISRCTN62510577., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/82/01) and is published in full in Health Technology Assessment ; Vol. 28, No. 23. See the NIHR Funding and Awards website for further award information.

Background: Prolapse affects 30-40% of women. Those using a pessary for prolapse usually receive care as an outpatient. This trial determined effectiveness and cost-effectiveness of pessary self-management (SM) vs clinic-based care (CBC) in relation to condition-specific quality of life (QoL)., Methods: Parallel-group, superiority randomised controlled trial, recruiting from 16 May 2018 to 7 February 2020, with follow-up to 17 September 2021. Women attending pessary clinics, ≥18 years, using a pessary (except Shelf, Gellhorn or Cube), with pessary retained ≥2 weeks were eligible. Limited manual dexterity; cognitive deficit; pregnancy; or requirement for non-English teaching were exclusions. SM group received a 30-min teaching session; information leaflet; 2-week follow-up call; and telephone support. CBC group received usual routine appointments. The primary clinical outcome was pelvic floor-specific QoL (PFIQ-7), and incremental net monetary benefit for cost-effectiveness, 18 months post-randomisation. Group allocation was by remote web-based application, minimised on age, user type (new/existing) and centre. Participants, intervention deliverers, researchers and the statistician were not blinded. The primary analysis was intention-to-treat based. Trial registration: https://doi.org/10.1186/ISRCTN62510577., Findings: The requisite 340 women were randomised (169 SM, 171 CBC) across 21 centres. There was not a statistically significant difference between groups in PFIQ-7 at 18 months (mean SM 32.3 vs CBC 32.5, adjusted mean difference SM-CBC -0.03, 95% CI -9.32 to 9.25). SM was less costly than CBC. The incremental net benefit of SM was £564 (SE £581, 95% CI -£576 to £1704). A lower percentage of pessary complications was reported in the SM group (mean SM 16.7% vs CBC 22.0%, adjusted mean difference -3.83%, 95% CI -6.86% to -0.81%). There was no meaningful difference in general self-efficacy. Self-managing women were more confident in self-management activities. There were no reported suspected unexpected serious adverse reactions, and 31 unrelated serious adverse events (17 SM, 14 CBC)., Interpretation: Pessary self-management is cost-effective, does not improve or worsen QoL compared to CBC, and has a lower complication rate., Funding: National Institute for Health and Care Research, Health Technology Assessment Programme (16/82/01)., Competing Interests: All authors declare a grant from National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme relating to the research described in the manuscript. In addition Lucy Dwyer reports being a member of the NICE guideline committee for non-surgical management and prevention of pelvic floor dysfunction and a member of the UK Clinical Guideline for best practice in the use of vaginal pessaries for pelvic organ prolapse committee; Aethele Khunda reports receiving an educational grant from Olympus Medical Systems to cover travel and accommodation costs to attend a laparoscopic urogynaecology workshop; Wael Agur reports grants from NIHR, consulting fees and payment for testimony from Oaklaw Consultancy Ltd., for Medico-legal Consultancy and financial/non-financial interest associated with Medical Innovation Systems; Karen Guerrero reports payment for expert testimony for the Medical Advisor NHS Scotland Central Legal Office and for NHS-funded study leave; Christine Hemming reports grants from NIHR HTA for two RCTs (11/129/183 and 07/60/18); John Norrie reports being a member of the following committees: NIHR CTU Standing Advisory Committee (2018-23), NIHR HTA & EME Editorial Board (2015–2019), EME Funding Committee Member (2019–2022), HTA General Committee (2016–2019), HTA Post-Funding Committee (2016–2019), HTA Funding Committee Policy Group (2016–2019), COVID-19 Reviewing (2020); Ranee Thakar reports a voluntary role at Royal College of Obstetricians and Gynaecologists; Rohna Kearney reports being topic lead for prolapse on NICE guideline NG123 published 2019; Angela Forrest reports payment for attending project meetings relating to the research; Suzanne Breeman reports grants from NIHR HTA for the VUE trial (11/129/183) and the PROSPECT trial (07/60/18 and NIHR133665). Suzanne Hagen, Carol Bugge, Andrew Elders, Helen Mason, Kirsteen Goodman, Doreen McClurg, Melanie Dembinsky, Lynn Melone, Catherine Best, Sarkis Manoukian, Margaret Graham, Jane Culverhouse and Mark Forrest have no additional disclosures to report relating to the manuscript., (© 2023 The Authors.)

This paper reports the synthesis, characterization and in vivo application of water-soluble supramolecular contrast agents (Mw: 5-5.6 kDa) for MRI obtained from β-cyclodextrin functionalized with different kinds of nitroxide radicals, both with piperidine structure (CD2 and CD3) and with pyrrolidine structure (CD4 and CD5). As to the stability of the radicals in presence of ascorbic acid, CD4 and CD5 have low second order kinetic constants (≤0.05 M -1  s -1 ) compared to CD2 (3.5 M -1  s -1 ) and CD3 (0.73 M -1  s -1 ). Relaxivity (r 1 ) measurements on compounds CD3-CD5 were carried out at different magnetic field strength (0.7, 3, 7 and 9.4 T). At 0.7 T, r 1 values comprised between 1.5 mM -1  s -1 and 1.9 mM -1  s -1 were found while a significant reduction was observed at higher fields (r 1 ≈0.6-0.9 mM -1  s -1 at 9.4 T). Tests in vitro on HEK293 human embryonic kidney cells, L929 mouse fibroblasts and U87 glioblastoma cells indicated that all compounds were non-cytotoxic at concentrations below 1 μmol mL -1 . MRI in vivo was carried out at 9.4 T on glioma-bearing rats using the compounds CD3-CD5. The experiments showed a good lowering of T 1 relaxation in tumor with a retention of the contrast for at least 60 mins confirming improved stability also in vivo conditions., (© 2023 The Authors. ChemPhysChem published by Wiley-VCH GmbH.)

Background: Pelvic organ prolapse (POP) is a common condition in women, where the downward descent of pelvic organs into the vagina causes symptoms which impacts quality of life. Vaginal pessaries offer an effective alternative to surgery for the management of POP. However, the need for regular follow-up can be burdensome for women and requires significant healthcare resources. The TOPSY study is a randomised controlled trial which aims to determine the clinical and cost-effectiveness of self-management of vaginal pessaries. This paper describes the theoretical and practical development of the self-management intervention., Methods: The intervention was developed using the MRC complex intervention framework, normalisation process theory (NPT) and self-management theory. The intervention aims to boost perceived self-efficacy in accordance with Bandura's social cognitive theory and is guided by the tasks and skills Lorig and Hollman describe as necessary to self-manage a health condition., Results: The TOPSY intervention was designed to support women to undertake the medical management, role management and emotional management of their pessary. The six self-management skills described by Lorig and Hollman: problem-solving, decision-making, resource utilisation, formation of a patient-provider partnership role, action planning and self-tailoring, are discussed in detail, including how women were supported to achieve each task within the context of pessary self-management. The TOPSY intervention includes a self-management support session with a pessary practitioner trained in intervention delivery, a follow-up phone call 2 weeks later and ongoing telephone or face-to-face support as required by the woman initiated by contacting a member of the research team., Conclusions: The TOPSY study intervention was developed utilising the findings from a prior service development project, intervention development and self-efficacy theory, relevant literature, clinician experience and feedback from pessary using women and members of the public. In 2022, the findings of the TOPSY study will provide further evidence to inform this important aspect of pessary management., Trial Registration: ISRCTN Registry ISRCTN62510577 . Registered on June 10, 2017., (© 2022. The Author(s).)

Pectin has found extensive interest in biomedical applications, including wound dressing, drug delivery, and cancer targeting. However, the low viscosity of pectin solutions hinders their applications in 3D bioprinting. Here, we developed multicomponent bioinks prepared by combining pectin with TEMPO-oxidized cellulose nanofibers (TOCNFs) to optimize the inks' printability while ensuring stability of the printed hydrogels and simultaneously print viable cell-laden inks. First, we screened several combinations of pectin (1%, 1.5%, 2%, and 2.5% w/v) and TOCNFs (0%, 0.5%, 1%, and 1.5% w/v) by testing their rheological properties and printability. Addition of TOCNFs allowed increasing the inks' viscosity while maintaining shear thinning rheological response, and it allowed us to identify the optimal pectin concentration (2.5% w/v). We then selected the optimal TOCNFs concentration (1% w/v) by evaluating the viability of cells embedded in the ink and eventually optimized the writing speed to be used to print accurate 3D grid structures. Bioinks were prepared by embedding L929 fibroblast cells in the ink printed by optimized printing parameters. The printed scaffolds were stable in a physiological-like environment and characterized by an elastic modulus of E = 1.8 ± 0.2 kPa. Cells loaded in the ink and printed were viable (cell viability >80%) and their metabolic activity increased in time during the in vitro culture, showing the potential use of the developed bioinks for biofabrication and tissue engineering applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pitton, Fiorati, Buscemi, Melone, Farè and Contessi Negrini.)

Background: Process evaluations have become a valued component, alongside clinical trials, of the wider evaluation of complex health interventions. They support understanding of implementation, and fidelity, related to the intervention and provide valuable insights into what is effective in a practical setting by examining the context in which interventions are implemented. The TOPSY study consists of a large multi-centre randomised controlled trial comparing the effectiveness of pessary self-management with clinic-based care in improving women's condition-specific quality of life, and a nested process evaluation. The process evaluation aims to examine and maximise recruitment to the trial, describe intervention fidelity and explore participants' and healthcare professionals' experiences., Methods: The trial will recruit 330 women from approximately 17 UK centres. The process evaluation uses a mixed-methods approach. Semi-structured interviews will be conducted with randomised women (18 per randomised group/n = 36), women who declined trial participation but agreed to interview (non-randomised women) (n = 20) and healthcare professionals recruiting to the trial (n ~ 17) and delivering self-management and clinic-based care (n ~ 17). The six internal pilot centres will be asked to record two to three recruitment discussions each (total n = 12-18). All participating centres will be asked to record one or two self-management teaching appointments (n = 30) and self-management 2-week follow-up telephone calls (n = 30). Process data (quantitative and qualitative) will be gathered in participant completed trial questionnaires. Interviews will be analysed thematically and recordings using an analytic grid to identify fidelity to the intervention. Quantitative analysis will be predefined within the process evaluation analysis plan., Discussion: The wide variety of pessary care delivered across the UK for women with pelvic organ prolapse presents specific localised contexts in which the TOPSY interventions will be implemented. Understanding this contextual variance is central to understanding how and in what circumstances pessary self-management can be implemented (should it be effective). The inclusion of non-randomised women provides an innovative way of collecting indispensable information about eligible women who decline trial participation, allowing broader contextualisation and considerations of generalisability of trial findings. Methodological insights from examination of recruitment processes and mechanisms have the potential to inform recruitment mechanisms and future recruitment strategies and study designs., Trial Registration: ISRCTN62510577 . Registered on 6 October 2017.

Background: Pelvic organ prolapse (or prolapse) is a common condition in women where the pelvic organs (bladder, bowel or womb) descend into the vagina and cause distressing symptoms that adversely affect quality of life. Many women will use a vaginal pessary to treat their prolapse symptoms. Clinic-based care usually consists of having a pessary fitted in a primary or secondary care setting, and returning approximately every 6 months for healthcare professional review and pessary change. However, it is possible that women could remove, clean and re-insert their pessary themselves; this is called self-management. This trial aims to assess if self-management of a vaginal pessary is associated with better quality of life for women with prolapse when compared to clinic-based care., Methods: This is a multicentre randomised controlled trial in at least 17 UK centres. The intervention group will receive pessary self-management teaching, a self-management information leaflet, a follow-up phone call and access to a local telephone number for clinical support. The control group will receive the clinic-based pessary care which is standard at their centre. Demographic and medical history data will be collected from both groups at baseline. The primary outcome is condition-specific quality of life at 18 months' post-randomisation. Several secondary outcomes will also be assessed using participant-completed questionnaires. Questionnaires will be administered at baseline, 6, 12 and 18 months' post-randomisation. An economic evaluation will be carried out alongside the trial to evaluate cost-effectiveness. A process evaluation will run parallel to the trial, the protocol for which is reported in a companion paper., Discussion: The results of the trial will provide robust evidence of the effectiveness of pessary self-management compared to clinic-based care in terms of improving women's quality of life, and of its cost-effectiveness., Trial Registration: ISRCTN Registry ISRCTN62510577 . Registered on June 10, 2017.

Cyclodextrins (CDs), a class of cyclic oligosaccharides formed by α-(1,4) linked glucopyranose units, were functionalized with (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) radicals to prepare water soluble supramolecular organic radical contrast agents (ORCAs) for the in vivo detection of glioma tumor in animal models. A first set of molecules (CDn1, n=6,7,8 is the number of both TEMPO and glucopyranose units) was studied by superconducting quantum interference devices (SQUID) magnetometry in order to define the role of the CD macrocycle on the effective magnetic moment (μ eff ). The μ eff value increased from 3.982 μ B (CD61) to 4.522 μ B (CD81) but was limited by intramolecular antiferromagnetic (AF) interactions. A set of water-soluble ORCAs (CDn8, n=6,7,8) was prepared by a sequence of thiol-ene and Cu(I)-catalyzed alkyne-azide "click" reactions. Their 1 H water relaxivities r 1 of these ORCAs were between 0.739 mM -1  s -1 (CD68) to 1.047 mM -1  s -1 (CD88) in D 2 O/H 2 O 9 : 1 (v : v) at 300 K. One of them (CD78) was tested on glioma-bearing rats with reduced side effects and good relaxivity in vivo., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Stable hydrogels with tunable rheological properties were prepared by adding Ca 2+ ions to aqueous dispersions of 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)-oxidized and ultra-sonicated cellulose nanofibers (TOUS-CNFs). The gelation occurred by interaction among polyvalent cations and the carboxylic units introduced on TOUS-CNFs during the oxidation process. Both dynamic viscosity values and pseudoplastic rheological behaviour increased by increasing the Ca 2+ concentration, confirming the cross-linking action of the bivalent cation. The hydrogels were proved to be suitable controlled release systems by measuring the diffusion coefficient of a drug model (ibuprofen, IB) by high-resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy. IB was used both as free molecule and as a 1:1 pre-formed complex with β-cyclodextrin (IB/β-CD), showing in this latter case a lower diffusion coefficient. Finally, the cytocompatibility of the TOUS-CNFs/Ca 2+ hydrogels was demonstrated in vitro by indirect and direct tests conducted on a L929 murine fibroblast cell line, achieving a percentage number of viable cells after 7 days higher than 70%.