Poly(N-isopropylacrylamide) and copolymers: a review on recent progresses in biomedical applications

The innate ability of poly(N-isopropylacrylamide) (PNIPAAm) thermo-responsive hydrogel to copolymerize and to graft synthetic polymers and biomolecules, in conjunction with the highly controlled methods of radical polymerization which are now available, have expedited the widespread number of papers published in the last decade—especially in the biomedical field. Therefore, PNIPAAm-based hydrogels are extensively investigated for applications on the controlled delivery of active molecules, in self-healing materials, tissue engineering, regenerative medicine, or in the smart encapsulation of cells. The most promising polymers for biodegradability enhancement of PNIPAAm hydrogels are probably poly(ethylene glycol) (PEG) and/or poly(e-caprolactone) (PCL), whereas the biocompatibility is mostly achieved with biopolymers. Ultimately, advances in three-dimensional bioprinting technology would contribute to the design of new devices and medical tools with thermal stimuli response needs, fabricated with PNIPAAm hydrogels.Peer ReviewedPostprint (published version

Polymers and plastics modified electrodes for biosensors: a review

Polymer materials offer several advantages as supports of biosensing platforms in terms of flexibility, weight, conformability, portability, cost, disposability and scope for integration. The present study reviews the field of electrochemical biosensors fabricated on modified plastics and polymers, focusing the attention, in the first part, on modified conducting polymers to improve sensitivity, selectivity, biocompatibility and mechanical properties, whereas the second part is dedicated to modified “environmentally friendly” polymers to improve the electrical properties. These ecofriendly polymers are divided into three main classes: bioplastics made from natural sources, biodegradable plastics made from traditional petrochemicals and eco/recycled plastics, which are made from recycled plastic materials rather than from raw petrochemicals. Finally, flexible and wearable lab-on-a-chip (LOC) biosensing devices, based on plastic supports, are also discussed. This review is timely due to the significant advances achieved over the last few years in the area of electrochemical biosensors based on modified polymers and aims to direct the readers to emerging trends in this field.Peer ReviewedPostprint (published version

Chitosan-derived nitrogen-doped carbon electrocatalyst for a sustainable upgrade of oxygen reduction to hydrogen peroxide in UV-assisted electro-Fenton water treatment

The urgency to move from critical raw materials to highly available and renewable feedstock is currently driving the scientific and technical developments. Within this context, the abundance of natural resources like chitosan paves the way to synthesize biomass-derived nitrogen-doped carbons. This work describes the synthesis of chitosan-derived N-doped mesoporous carbon in the absence (MC-C) and presence (N-MC-C) of 1,10-phenanthroline, which acted as both a porogen agent and a second nitrogen source. The as-prepared MC-C and N-MC-C were thoroughly characterized and further employed as catalytic materials in gas-diffusion electrodes (GDEs), aiming to develop a sustainable alternative to conventional GDEs for H2O2 electrogeneration and photoelectro-Fenton (PEF) treatment of a drug pollutant. N-MC-C presented a higher content of key surface N-functionalities like the pyrrole group, as well as an increased graphitization degree and surface area (63 vs 6 m2/g), comparable to commercial carbon black. These properties entailed a superior activity of N-MC-C for the oxygen reduction reaction, as confirmed from its voltammetric behavior at a rotating ring-disk electrode. The GDE prepared with the N-MC-C catalyst showed greater H2O2 accumulation, attaining values close to those obtained with a commercial GDE. N-MC-C- and MC-C-derived GDEs were employed to treat drug solutions at pH 3.0 by the PEF process, which outperformed electro-oxidation. The fastest drug removal was achieved using N-MC-C, requiring only 16 min at 30 mA/cm2 instead of 20 min required with MC-C. The replacement of the dimensionally stable anode by a boron-doped diamond accelerated the degradation process, reaching an almost complete mineralization in 360 min. The main degradation products were identified, revealing the formation of six different aromatic intermediates, alongside five aliphatic compounds that comprised three nitrogenated structures. The initial N was preferentially converted into ammonium.Peer ReviewedPostprint (published version

Polypropylene mesh for hernia repair with controllable cell adhesion/de-adhesion properties

Herein, a versatile bilayersystem, composed by a polypropylene(PP)mesh and a covalently bonded poly(N-isopropylacrylamide) (PNIPAAm) hydrogel, is reported. The cell adhesion mechanism was successfully modulated by controlling the architecture of the hydrogel in terms of duration of PNIPAAm graftingtime, crosslinker content, and temperature of material exposure in PBS solutions (belowandabove the LCST of PNIPAAm). The best in vitroresults with fibroblast (COS-1) and epithelial (MCF-7) cells was obtained with a mesh modified with porous iPP-g-PNIPAAm bilayer system, prepared via PNIPAAm grafting for 2 h at the lowest N,N'-methylene bis(acrylamide) (MBA)concentration (1 mM). Under these conditions, the detachment of the fibroblast-like cells was 50% lower than that of the control, after 7 days of cell incubation, which represents a high de-adhesionof cellsin a short period. Moreover, the whole system showed an excellent stability in dry or wet media, proving that the thermosensitive hydrogel was well adhered to the polymer surface, after PP fibreactivation by cold plasma. This study opens new insights on the development of anti-adherent meshes for abdominal hernia repairs.Peer ReviewedPublished versio

Synthesis of polymer nanogels by electro-Fenton process: investigation of the effect of main operation parameters

Recently, electro-Fenton (EF) process has been shown as a promising, facile, effective, low cost and environmentally-friendly alternative for synthesizing polymer nanogels suitable as biocompatible nanocarriers for emerging biomedical applications. Here, the electrochemically-assisted modification of poly(vinylpyrrolidone) (PVP) by EF process was studied to assess the role of key operation parameters for a precise modulation of polymer crosslinking and its functionalization with -COOH and succinimide groups. The dimensions of the nanogels, in terms of hydrodynamic radius (Rh) and weight-average molecular weight (Mw), can be tuned up by controlling the electrolysis time, current density (j) and PVP and Fe2+ concentrations, as demonstrated via dynamic and static light scattering and gel permeation chromatography analysis. Using PVP at 0.25 wt.%, Fe2+ at 0.5-1.0 mmol dm-3 and low j, short treatment times induced intramolecular crosslinking with chain scission, allowing size reduction of PVP particles from 24 to 9-10 nm. Longer reaction times and higher PVP and Fe2+ contents favored intermolecular crosslinking ending in Mw values higher than the initial 3.95×105 g mol-1. An excessive ¿OH dose from a too high circulated charge (Q), i.e., too prolonged electrolysis time even at low j or too high j even for short time, promoted intramolecular crosslinking (Rh ~ 10-12 nm) along with a very significant chain scission probably owing to the loss of mobility of the three-dimensional nanogel network. In conclusion, EF allowed transforming the architecture of linear, inert PVP chains into a functionalized nanogel with -COOH and succinimide groups that have great potential for further conjugation

Combining 2D organic and 1D inorganic nanoblocks to develop free-standing hybrid nanomembranes for conformable biosensors

We report a simple approach to fabricate free-standing perforated 2D nanomembranes hosting well-ordered 1D metallic nanostructures to obtain hybrid materials with nanostructured surfaces for flexible electronics. Nanomembranes are formed by alternatively depositing perforated poly(lactic acid) (PLA) and poly(3,4-ethylenedioxythiophene) layers. Copper metallic nanowires (NWs) were incorporated into the nanoperforations of the top PLA layer by electrodeposition and further coated with silver via a transmetallation reaction. The combination of 2D polymeric nanomembranes and aligned 1D metallic NWs allows merging the flexibility and conformability of the ultrathin soft polymeric nanomembranes with the good electrical properties of metals for biointegrated electronic devices. Thus, we were able to tailor the nanomembrane surface chemistry as it was corroborated by SEM, EDX, XPS, CV, EIS and contact angle. The obtained hybrid nanomembranes were flexible and conformable showing sensing capacity towards H2O2 with good linear concentration range (0.35–10 mM), sensitivity (120 µA cm?2 mM?1) and limit of detection (7 ?m). Moreover, the membranes showed good stability, reproducibility and selectivity towards H2O2

Crosslinking of poly(vinylpyrrolidone) activated by electrogenerated hydroxyl radicals: a first step towards a simple and cheap synthetic route of nanogel vectors

A facile electrosynthesis route for the preparation of polymer nanogels based on the in situ production of hydroxyl radicals is reported for the first time. Electro-Fenton process with continuous H2O2 electrogeneration and Fe2+ regeneration performs better than electro-oxidation with a boron-doped diamond or dimensionally stable anode for promoting crosslinking of poly(vinylpyrrolidone)

Facile crosslinking of poly(vinylpyrrolidone) by electro-oxidation with IrO2-based anode under potentiostatic conditions

The modification of polymer architectures by reaction with chemically adsorbed hydroxyl radicals has been thoroughly investigated by electrolyzing dilute aqueous solutions of the biocompatible polymer poly(vinylpyrrolidone) (PVP), using an undivided electrolytic cell with a Ti/IrO2-Ta2O5 (DSA®) anode. Several electrolyses were performed to assess the influence of the applied potential, the circulated charge and the PVP concentration, which was always kept low to avoid chain overlapping. From the results obtained, it can be concluded that the electro-oxidation of PVP solutions using a cheap anode is an effective method to crosslink initially isolated polymer chains, eventually increasing the size of their random coils. Furthermore, the average size of the modified macromolecules can be controlled by tuning the electrode potential and/or the current density and the circulated charge. At high anodic potential values, the hydroxyl radicals formed at DSA® were also effective to generate reactive functional groups on the PVP backbone, which is a very interesting feature for future biomedical applications

A flexible, smart and self-evolving actuator based on polypropylene mesh for hernia repair and a thermo-sensitive gel

Here, a smart mesh actuator, able to self-evolve under temperature and humidity control,has been developed. Thermo-responsive poly(N-isopropylacrylamide) (PNIPAAm)-based materialsare widely appliedin biomedical field owingto theirexcellent biocompatibility and abrupt conformational change at a critical temperature very close to that of human body(~32 °C) [1-2]. The actuator is based on PNIPAAmgrafted on a commercial polypropylene (PP)mesh used for hernia repair[3].Flexible devices composed of PP-g-PNIPAAm arranged inmonolayer (one layer of PNIPAAm) and bilayer (two layers of PNIPAAm) conformationswere synthesized. The microstructureof the gel chains (chain length measurements) and the macromotion(unfolding angle observations) behavior of the composite mesh in water and air at different temperatures were studied. The motion is affected by the amount and the position of the gel (upper fibers or among them) and by the crosslinking degree. For the first time,a self-evolving motion sensor based on commercial hernia repair mesh has beenproduced by using a biocompatible hydrogel. The strategy can be easily extrapolated to complex mesh architecturesPostprint (published version