Novel Building Blocks for Molecular Imprinting: Pyridine-Based Binding Monomers and Bio-Renewable Cross-Linkers

Molecular imprinting refers to the creation of synthetic materials with built-in memory for a selected target (atom, ion, molecule, complex or a molecular, ionic or macromolecular assembly, including micro-organisms) used as a template to direct the synthesis of the material, a Molecularly Imprinted Polymer (MIP). Here we would like to report on the development of Molecularly Imprinted Polymers (MIPs) for the recognition of molecules of biological/pharmaceutical interest such as biotin and barbiturates using a series of pyridine-based binding monomers which contain hydrogen bonding arrays complementary to their particular targets. MIPs are already widely used for the creation of artificial receptors that will be less expensive, more stable and far more easily reusable compared to their natural counterparts. However there remains plenty of room for improvement in the affinity and selectivity exhibited by MIPs. The common use of commercially available monomers, such as methacrylic acid, is a limitation in the imprinting process. The design of new functional monomers for stoichiometric non-covalent molecular imprinting can enhance the selectivity and specificity of the MIP towards a specific target by decreasing the level of non-specific binding in the polymer, which is generally caused by the use of an excess of functional monomer in the prepolymerisation mixture. Bio-renewable cross-linkers were also synthesised from isomannide, isosorbide and 2,5-bis(hydroxymethyl)furan as a greener and bio-sustainable alternative to ethylene glycol dimethacrylate (EGDMA) in the Molecular Imprinting technology. Herein we will report on the preparation of novel MIPs selective towards uridine prepared using BAAPy as the functional monomer, 2′,3′,5′-tri-O-acetyluridine (TAU) as the dummy template and three acrylate- and methacrylate-based biosustainable crosslinking monomers prepared by esterification of isosorbide (1,4:3,6 dianhydrosorbitol), isomannide (1,4:3,6-dianhydromannitol) and 2,5- bis(hydroxymethyl)furan. The selectivity, specificity and capacity of the reported polymers towards their imprinted templates and similar analytes were evaluated through chromatography and rebinding studies

Assessing the Social and Environmental Impact of Healthcare Technologies: Towards an Extended Social Return on Investment

Stroke is the third leading cause of death and disability overall worldwide. Upper limb impairment is a common consequence for stroke survivors, having negative impact on their quality of life. Robotic rehabilitation, through repetitive and monitored movements, can improve their status. Developed by a team of researchers at Politecnico di Milano, AGREE is an exoskeleton for upper limb rehabilitation at the stage gate between translational research and clinical validation. Since the cost of this device is particularly high, the present study aimed to provide a framework for assessing its value. The Social Return on Investment (SROI) method, able to grasp the economic, social and environmental impact of an activity, was applied, using expert opinions of a pool of clinical engineers and healthcare professionals from different Italian hospitals to obtain information. Environmental impacts were estimated through Life Cycle Assessment in terms of CO2 emissions and incorporated in the analysis. Considering a 5-year period, the SROI for a single exoskeleton was 3.75:1, and the SROI for the number of exoskeletons projected to be sold was 2.868:1, thus resulting largely in value for money. This study provides a model for combining economic, social and environmental outcomes that, besides contributing to theory, could be useful for decision-making

Recent advances in smart biotechnology: Hydrogels and nanocarriers for tailored bioactive molecules depot

Over the past ten years, the global biopharmaceutical market has remarkably grown, with ten over the top twenty worldwide high performance medical treatment sales being biologics. Thus, biotech R&D (research and development) sector is becoming a key leading branch, with expanding revenues. Biotechnology offers considerable advantages compared to traditional therapeutic approaches, such as reducing side effects, specific treatments, higher patient compliance and therefore more effective treatments leading to lower healthcare costs. Within this sector, smart nanotechnology and colloidal self-assembling systems represent pivotal tools able to modulate the delivery of therapeutics. A comprehensive understanding of the processes involved in the self assembly of the colloidal structures discussed therein is essential for the development of relevant biomedical applications. In this review we report the most promising and best performing platforms for specific classes of bioactive molecules and related target, spanning from siRNAs, gene/plasmids, proteins/growth factors, small synthetic therapeutics and bioimaging probes.Istituto Italiano di Tecnologia (IIT)COST Action [CA 15107]People Program (Marie Curie Actions) of the European Union's Seventh Framework Program under REA [606713 BIBAFOODS]Portuguese Foundation for Science and Technology (FCT) [PTDC/AGR-TEC/4814/2014, IF/01005/2014]Fundacao para a Ciencia e Tecnologia [SFRH/BPD/99982/2014]Danish National Research Foundation [DNRF 122]Villum Foundation [9301]Italian Ministry of Instruction, University and Research (MIUR), PRIN [20109PLMH2]"Fondazione Beneficentia Stiftung" VaduzFondo di Ateneo FRAFRAinfo:eu-repo/semantics/publishedVersio

Polydopamine-Coated Poly-Lactic Acid Aerogels as Scaffolds for Tissue Engineering Applications

Poly-L-lactic acid (PLLA) aerogel-based scaffolds were obtained from physical PLLA gels containing cyclopentanone (CPO) or methyl benzoate (BzOMe) molecules. An innovative single step method of solvent extraction, using supercritical CO2, was used to achieve cylindrical monolithic aerogels. The pore distribution and size, analyzed by SEM microscopy, were found to be related to the crystalline forms present in the physical nodes that hold the gels together, the stable alpha'-form and the metastable co-crystalline epsilon-form, detected in the PLLA/BzOMe and PLLA/CPO aerogels, respectively. A higher mechanical compressive strength was found for the PLLA/CPO aerogels, which exhibit a more homogenous porosity. In vitro biocompatibility tests also indicated that monolithic PLLA/CPO aerogels exhibited greater cell viability than PLLA/BzOMe aerogels. An improved biocompatibility of PLLA/CPO monolithic aerogels was finally observed by coating the surface of the aerogels with polydopamine (PDA) obtained by the in situ polymerization of dopamine (DA). The synergistic effect of biodegradable polyester (PLLA) and the biomimetic interface (PDA) makes this new 3D porous scaffold, with porosity and mechanical properties that are tunable based on the solvent used in the preparation process, attractive for tissue engineering applications

Mixtures of Chemical Pollutants at European Legislation Safety Concentrations: How Safe Are They?

The risk posed by complex chemical mixtures in the environment to wildlife and humans is increasingly debated, but has been rarely tested under environmentally relevant scenarios. To address this issue, two mixtures of 14 or 19 substances of concern (pesticides, pharmaceuticals, heavy metals, polyaromatic hydrocarbons, a surfactant, and a plasticizer), each present at its safety limit concentration imposed by the European legislation, were prepared and tested for their toxic effects. The effects of the mixtures were assessed in 35 bioassays, based on 11 organisms representing different trophic levels. A consortium of 16 laboratories was involved in performing the bioassays. The mixtures elicited quantifiable toxic effects on some of the test systems employed, including i) changes in marine microbial composition, ii) microalgae toxicity, iii) immobilization in the crustacean Daphnia magna, iv) fish embryo toxicity, v) impaired frog embryo development, and vi) increased expression on oxidative stress-linked reporter genes. Estrogenic activity close to regulatory safety limit concentrations was uncovered by receptor-binding assays. The results highlight the need of precautionary actions on the assessment of chemical mixtures even in cases where individual toxicants are present at seemingly harmless concentration

Mixtures of chemical pollutants at European legislation safety concentrations: how safe are they?

The risk posed by complex chemical mixtures in the environment to wildlife and humans is increasingly debated, but has been rarely tested under environmentally relevant scenarios. To address this issue, two mixtures of 14 or 19 substances of concern (pesticides, pharmaceuticals, heavy metals, polyaromatic hydrocarbons, a surfactant, and a plasticizer), each present at its safety limit concentration imposed by the European legislation, were prepared and tested for their toxic effects. The effects of the mixtures were assessed in 35 bioassays, based on 11 organisms representing different trophic levels. A consortium of 16 laboratories was involved in performing the bioassays. The mixtures elicited quantifiable toxic effects on some of the test systems employed, including i) changes in marine microbial composition, ii) microalgae toxicity, iii) immobilization in the crustacean Daphnia magna, iv) fish embryo toxicity, v) impaired frog embryo development, and vi) increased expression on oxidative stress-linked reporter genes. Estrogenic activity close to regulatory safety limit concentrations was uncovered by receptor-binding assays. The results highlight the need of precautionary actions on the assessment of chemical mixtures even in cases where individual toxicants are present at seemingly harmless concentrations

Novel Building Blocks for Molecular Imprinting: Pyridine-Based Binding Monomers and Bio-Renewable Cross-Linkers

Molecular imprinting refers to the creation of synthetic materials with built-in memory for a selected target (atom, ion, molecule, complex or a molecular, ionic or macromolecular assembly, including micro-organisms) used as a template to direct the synthesis of the material, a Molecularly Imprinted Polymer (MIP). Here we would like to report on the development of Molecularly Imprinted Polymers (MIPs) for the recognition of molecules of biological/pharmaceutical interest such as biotin and barbiturates using a series of pyridine-based binding monomers which contain hydrogen bonding arrays complementary to their particular targets. MIPs are already widely used for the creation of artificial receptors that will be less expensive, more stable and far more easily reusable compared to their natural counterparts. However there remains plenty of room for improvement in the affinity and selectivity exhibited by MIPs. The common use of commercially available monomers, such as methacrylic acid, is a limitation in the imprinting process. The design of new functional monomers for stoichiometric non-covalent molecular imprinting can enhance the selectivity and specificity of the MIP towards a specific target by decreasing the level of non-specific binding in the polymer, which is generally caused by the use of an excess of functional monomer in the prepolymerisation mixture. Bio-renewable cross-linkers were also synthesised from isomannide, isosorbide and 2,5-bis(hydroxymethyl)furan as a greener and bio-sustainable alternative to ethylene glycol dimethacrylate (EGDMA) in the Molecular Imprinting technology. Herein we will report on the preparation of novel MIPs selective towards uridine prepared using BAAPy as the functional monomer, 2′,3′,5′-tri-O-acetyluridine (TAU) as the dummy template and three acrylate- and methacrylate-based biosustainable crosslinking monomers prepared by esterification of isosorbide (1,4:3,6 dianhydrosorbitol), isomannide (1,4:3,6-dianhydromannitol) and 2,5- bis(hydroxymethyl)furan. The selectivity, specificity and capacity of the reported polymers towards their imprinted templates and similar analytes were evaluated through chromatography and rebinding studies

Rewiring care delivery through Digital Therapeutics (DTx): a machine learning-enhanced assessment and development (M-LEAD) framework

Abstract Background Digital transformation has sparked profound change in the healthcare sector through the development of innovative digital technologies. Digital Therapeutics offer an innovative approach to disease management and treatment. Care delivery is increasingly patient-centered, data-driven, and based on real-time information. These technological innovations can lead to better patient outcomes and support for healthcare professionals, also considering resource scarcity. As these digital technologies continue to evolve, the healthcare field must be ready to integrate them into processes to take advantage of their benefits. This study aims to develop a framework for the development and assessment of Digital Therapeutics. Methods The study was conducted relying on a mixed methodology. 338 studies about Digital Therapeutics resulting from a systematic literature review were analyzed using descriptive statistics through RStudio. Machine learning algorithms were applied to analyze variables and find patterns in the data. The results of these analytical analyses were summarized in a framework qualitatively tested and validated through expert opinion elicitation. Results The research provides M-LEAD, a Machine Learning-Enhanced Assessment and Development framework that recommends best practices for developing and assessing Digital Therapeutics. The framework takes as input Digital Therapeutics characteristics, regulatory aspects, study purpose, and assessment domains. The framework produces as outputs recommendations to design the Digital Therapeutics study characteristics. Conclusions The framework constitutes the first step toward standardized guidelines for the development and assessment of Digital Therapeutics. The results may support manufacturers and inform decision-makers of the relevant results of the Digital Therapeutics assessment

Toxicity Assessment of Carbon Nanomaterials in Zebrafish during Development

Carbon nanomaterials (CNMs) are increasingly employed in nanomedicine as carriers for intracellular transport of drugs, imaging probes, and therapeutics agents, thanks to their unique optical and physicochemical properties. However, a better understanding about the effects of CNMs on a vertebrate model at the whole animal level is required. In this study, we compare the toxicity of oxidized carbon nano-onions (oxi-CNOs), oxidized carbon nano-horns (oxi-CNHs) and graphene oxide (GO) in zebrafish (Danio rerio). We evaluate the possible effects of these nanomaterials on zebrafish development by assessing different end-points and exposure periods