Electrochemically Mediated Atom Transfer Radical Polymerization Driven by Alternating Current.

Alternating current (AC) and pulsed electrolysis are gaining traction in electro(organic) synthesis due to their advantageous characteristics. We employed AC electrolysis in electrochemically mediated Atom Transfer Radical Polymerization (eATRP) to facilitate the regeneration of the activator CuI complex on Cu0 electrodes. Additionally, Cu0 served as a slow supplemental activator and reducing agent (SARA ATRP), enabling the activation of alkyl halides and the regeneration of the CuI activator through a comproportionation reaction. We harnessed the distinct properties of Cu0 dual regeneration, both chemical and electrochemical, by employing sinusoidal, triangular, and square-wave AC electrolysis alongside some of the most active ATRP catalysts available. Compared to linear waveform (DC electrolysis) or SARA ATRP (without electrolysis), pulsed and AC electrolysis facilitated slightly faster and more controlled polymerizations of acrylates. The same AC electrolysis conditions could successfully polymerize eleven different monomers across different mediums, from water to bulk. Moreover, it proved effective across a spectrum of catalyst activity, from low-activity Cu/2,2-bipyridine to highly active Cu complexes with substituted tripodal amine ligands. Chain extension experiments confirmed the high chain-end fidelity of the produced polymers, yielding functional and high molecular-weight block copolymers. SEM analysis indicated the robustness of the Cu0 electrodes, sustaining at least 15 consecutive polymerizations.

Glycopolymers Mediate Suicide Gene Therapy in ASGPR-Expressing Hepatocellular Carcinoma Cells in Tandem with Docetaxel.

Cationic glycopolymers stand out as gene delivery nanosystems due to their inherent biocompatibility and high binding affinity to the asialoglycoprotein receptor (ASGPR), a target receptor overexpressed in hepatocellular carcinoma (HCC) cells. However, their synthesis procedure remains laborious and complex, with problems of solubilization and the need for protection/deprotection steps. Here, a mini-library of well-defined poly(2-aminoethyl methacrylate hydrochloride-co-poly(2-lactobionamidoethyl methacrylate) (PAMA-co-PLAMA) glycopolymers was synthesized by activators regenerated by electron transfer (ARGET) ATRP to develop an efficient gene delivery nanosystem. The glycoplexes generated had suitable physicochemical properties and showed high ASGPR specificity and high transfection efficiency. Moreover, the HSV-TK/GCV suicide gene therapy strategy, mediated by PAMA144-co-PLAMA19-based nanocarriers, resulted in high antitumor activity in 2D and 3D culture models of HCC, which was significantly enhanced by the combination with small amounts of docetaxel. Overall, our results demonstrated the potential of primary-amine polymethacrylate-containing-glycopolymers as HCC-targeted suicide gene delivery nanosystems and highlight the importance of combined strategies for HCC treatment.

Catalytic Halogen Exchange in Supplementary Activator and Reducing Agent Atom Transfer Radical Polymerization for the Synthesis of Block Copolymers.

Synthesis of block copolymers (BCPs) by catalytic halogen exchange (cHE) is reported, using supplemental activator and reducing agent Atom Transfer Radical Polymerization (SARA ATRP). The cHE mechanism is based on the use of a small amount of a copper catalyst in the presence of a suitable excess of halide ions, for the synthesis of block copolymers from macroinitiators with monomers of mismatching reactivity. cHE overcomes the problem of inefficient initiation in block copolymerizations in which the second monomer provides dormant species that are more reactive than the initiator. Model macroinitiators with low dispersity are prepared and extended to afford well-defined block copolymers of various compositions. Combined cHE/SARA ATRP is therefore a simple and potent polymerization tool for the copolymerization of a wide range of monomers allowing the production of tailored block copolymers.

Poly(ethylene glycol)- block-poly(2-aminoethyl methacrylate hydrochloride)-Based Polyplexes as Serum-Tolerant Nanosystems for Enhanced Gene Delivery.

Incorporation of poly(ethylene glycol) (PEG) into polyplexes has been used as a promising approach to enhance their stability and reduce unwanted interactions with biomolecules. However, this strategy generally has a negative influence on cellular uptake and, consequently, on transfection of target cells. In this work, we explore the effect of PEGylation on biological and physicochemical properties of poly(2-aminoethyl methacrylate) (PAMA)-based polyplexes. For this purpose, different tailor-made PEG- b-PAMA block copolymers, and the respective homopolymers, were synthesized using the controlled/"living" radical polymerization method based on activators regenerated by electron transfer atom transfer radical polymerization. The obtained data show that PEG- b-PAMA-based polyplexes exhibited a much better transfection activity/cytotoxicity relationship than the corresponding non-PEGylated nanocarriers. The best formulation, prepared with the largest block copolymer (PEG45- b-PAMA168) at a 25:1 N/P ratio, presented a 350-fold higher transfection activity in the presence of serum than that obtained with polyplexes generated with the gold standard bPEI. This higher transfection activity was associated to an improved capability to overcome the intracellular barriers, namely the release from the endolysosomal pathway and the vector unpacking and consequent DNA release from the nanosystem inside cells. Moreover, these nanocarriers exhibit suitable physicochemical properties for gene delivery, namely reduced sizes, high DNA protection, and colloidal stability. Overall, these findings demonstrate the high potential of the PEG45- b-PAMA168 block copolymer as a gene delivery system.

Increasing the Antimicrobial Activity of Amphiphilic Cationic Copolymers by the Facile Synthesis of High Molecular Weight Stars by Supplemental Activator and Reducing Agent Atom Transfer Radical Polymerization.

Infections caused by bacteria represent a great motif of concern in the health area. Therefore, there is a huge demand for more efficient antimicrobial agents. Antimicrobial polymers have attracted special attention as promising materials to prevent infectious diseases. In this study, a new polymeric system exhibiting antimicrobial activity against a range of Gram-positive and Gram-negative bacterial strains at micromolar concentrations (e.g., 0.8 µM) was developed. Controlled linear and star-shaped copolymers, comprising hydrophobic poly(butyl acrylate) (PBA) and cationic poly(3-acrylamidopropyl)trimethylammonium chloride) (PAMPTMA) segments, were obtained by supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP) at 30 °C. The antibacterial activity of the polymers was studied by varying systematically the molecular weight (MW), hydrophilic/hydrophobic balance, and architecture. The MW was found to exert the greatest influence on the antimicrobial activity of the polymers, with minimum inhibitory concentration values decreasing with increasing MW. Live/dead membrane integrity assays and scanning electron microscopy analysis confirmed the bactericidal character of the synthesized PAMPTMA- (b)co-PBA polymers.

Combination of Poly[(2-dimethylamino)ethyl methacrylate] and Poly(ß-amino ester) Results in a Strong and Synergistic Transfection Activity.

This work reports an innovative and very effective gene delivery nanosystem, based on the combination of poly[(2-dimethylamino)ethyl methacrylate] (PDMAEMA) and poly(ß-amino ester) (PßAE) homopolymers, that has the capacity to efficiently deliver genetic material into target cells, even in the presence of serum. The best formulation, prepared with the combination PDMAEMA/4PßAE at the 25/1 nitrogen/phosphate (N/P) ratio, presented a 700-fold and 220-fold higher transfection activity than that obtained with branched polyethylenimine (PEI)-based polyplexes and block copolymer-based polyplexes, respectively. This new nanocarrier revealed high transgene expression in different human cells, including hard-to-transfect normal human astrocytes. The polyplexes presented high protection of genetic material and reduced sizes, which are suitable physicochemical properties for in vivo applications. Overall, this study demonstrates that the combination of PDMAEMA and PßAE homopolymers resulted in a noticeable and synergistic effect in terms of transfection activity, without causing substantial toxicity, constituting a new platform for the development of gene delivery nanosystems.

Increasing the Bile Acid Sequestration Performance of Cationic Hydrogels by Using an Advanced/Controlled Polymerization Technique.

PURPOSE: To investigate the influence of the polymerization technique and the content of hydroxyl groups on the performance of new bile acid sequestrants based on PAMPMTA-co-PHEA (PAMPTMA: poly((3-acrylamidopropyl)trimethylammonium chloride); PHEA: poly(2-hydroxyethyl acrylate)) hydrogels. METHODS: PAMPMTA-co-PHEA hydrogels were prepared using either free radical polymerization or supplemental activator and reducing agent atom transfer radical polymerization. The chemical structure and composition of the hydrogels was confirmed by both FTIR and ssNMR. The binding of sodium cholate as the model bile salt was evaluated in simulated intestinal fluid using HPLC. The degradation of the polymers was evaluated in vitro in solutions mimicking the gastrointestinal tract environment. RESULTS: The binding showed that an increase of the amount of HEA in the hydrogel lead to a decrease of the binding capacity. In addition, it was demonstrated for the first time that the hydrogels produced by SARA ATRP presented a higher binding capacity than similar ones produced by FRP. Finally, it was observed that copolymers of PAMPTMA-co-PHEA showed no sign of degradation in solutions mimicking both the stomach and the intestine environment. CONCLUSIONS: The use of an advanced polymerization technique, such as the SARA ATRP, could be beneficial for the preparation of BAS with enhanced performance.

Outlining critical quality attributes (CQAs) as guidance for the development of orodispersible films.

CONTEXT: Orodispersible films have gained increasing relevance as a novel dosage form. Associated to their particular processing and multicomponent composition, there are a vast number of reasons to establish helpful development guidance, gathering simultaneously the recent pharmaceutical regulatory trends. OBJECTIVE: This study aimed characterize marketed orodispersible films in order to provide essential information about a clear definition of product critical quality attributes (CQAs). MATERIALS AND METHODS: Several commercial orodispersible films were evaluated in terms of thickness, residual water content, disintegration time and mechanical and thermal properties. RESULTS: The orodispersible films exhibit a broad range of thickness [40-140 µm], probably associated with the height gap used on the cast of orodispersible films production. The majority of orodispersible films dissolved within [32-105s]. In general, a broad range of values were found for all the properties studied, residual water content [2.91-9.75%], Young's Modulus [51.25-1827 Mpa], tensile strength [1.47-33.91 Mpa] and tensile strain [0.32-38.2%]. DISCUSSION AND CONCLUSIONS: Despite the orodispersible films' complex composition, it was possible to establish correlations about the impact of the main excipients on the final product characteristics. Acceptable values for the CQAs were also defined, working as acceptance criteria for the development of new oral film formulations.

Preparation of robust polyamide microcapsules by interfacial polycondensation of p-phenylenediamine and sebacoyl chloride and plasticization with oleic acid.

Microcapsules produced by interfacial polycondensation of p-phenylenediamine (PPD) and sebacoyl chloride (SC) were studied. The products were characterized in terms of morphology, mean diameter and effectiveness of dodecane encapsulation. The use of Tween 20 as dispersion stabilizer, in comparison with polyvinyl alcohol (PVA), reduced considerably the mean diameter of the microcapsules and originated smoother wall surfaces. When compared to ethylenediamine (EDA), microcapsules produced with PPD monomer were more rigid and brittle, prone to fracture during processing and ineffective retention of the core liquid. The use of diethylenetriamine (DETA) cross-linker in combination with PPD did not decrease capsule fragility. On the other hand, addition of a small fraction of oleic acid to the organic phase remarkably improved wall toughness and lead to successful encapsulation of the core-oil. Oleic acid is believed to act as a plasticizer. Its incorporation in the polymeric wall was demonstrated by FTIR and (1)H-NMR.

Recycling Polyethylene/Polyamide Multilayer Films with Poly(isoprene-g-Maleic Anhydride) Compatibilizer.

Polymers generally form incompatible mixtures that make the process of recycling difficult, especially the mechanical recycling of mixed plastic waste. One of the most commonly used films in the packaging industry is multilayer films, mainly composed of polyethylene (PE) and polyamide (PA). Recycling these materials with such different molecular structures requires the use of compatibilizers to minimize phase separation and obtain more useful recycled materials. In this work, commercial polyisoprene-graft-maleic anhydride (PI-g-MA) was tested as a compatibilizer for a blend of PE and PA derived from the mechanical recycling of PE/PA multilayer films. Different amounts of PI-g-MA were tested, and the films made with 1.5% PI-g-MA showed the best results in terms of mechanical properties and dart impact. The films were also characterized thermally via thermogravimetric analysis (TG) and differential scanning calorimetry (DSC), using Fourier-transform infrared spectroscopy (FTIR), and morphologically using a scanning electron microscope (SEM). Other parameters, such as tearing and perforation, were analyzed.

Fast-Gelling Polyethylene Glycol/Polyethyleneimine Hydrogels Degradable by Visible-Light.

The treatment of burn wounds remains a clinical challenge due to the need for repeated dressings changes. Therefore, the development of a dressing system that can be atraumatically removed from the wound bed can be considered a breakthrough and improve treatment times. In this work, the development of an injectable, fast-gelling hydrogel is proposed that can change its mechanical properties when exposed to visible light. The hydrogels are prepared by a "click" amino-yne reaction between poly(ethylene glycol) (PEG) functionalized with propiolic acid and the amino groups of poly(ethyleneimine) (PEI). The hydrogels exhibit a fast gelation time, which can be adjusted by changing the weight percentage and molecular weight of the precursors. They also exhibit good swelling ability and adhesion to living tissues. More importantly, their mechanical properties changed upon irradiation with green light. This loss of properties is achieved by a 1 O2 -mediated mechanism, as confirmed by the degradation of the ß-aminoacrylate linker. Moreover, the in vitro cell compatibility results of the hydrogels and their degradation products show good cytocompatibility. Therefore, it is believed that these hydrogels can be considered as materials with great potential for an innovative strategy for the treatment of burn wounds.

Targeted downregulation of MYC mediated by a highly efficient lactobionic acid-based glycoplex to enhance chemosensitivity in human hepatocellular carcinoma cells.

The chemosensitization of tumor cells by gene therapy represents a promising strategy for hepatocellular carcinoma (HCC) treatment. In this regard, HCC-specific and highly efficient gene delivery nanocarriers are urgently needed. For this purpose, novel lactobionic acid-based gene delivery nanosystems were developed to downregulate c-MYC expression and sensitize tumor cells to low concentration of sorafenib (SF). A library of tailor-made cationic glycopolymers, based on poly(2-aminoethyl methacrylate hydrochloride) (PAMA) and poly(2-lactobionamidoethyl methacrylate) (PLAMA) were synthesized by a straightforward activators regenerated by electron transfer atom transfer radical polymerization. The nanocarriers prepared with PAMA114-co-PLAMA20 glycopolymer were the most efficient for gene delivery. These glycoplexes specifically bound to the asialoglycoprotein receptor and were internalized through the clathrin-coated pit endocytic pathway. c-MYC expression was significantly downregulated by MYC short-hairpin RNA (MYC shRNA), resulting in efficient inhibition of tumor cells proliferation and a high levels apoptosis in 2D and 3D HCC-tumor models. Moreover, c-MYC silencing increased the sensitivity of HCC cells to SF (IC50 for MYC shRNA + SF 1.9 µM compared to 6.9 µM for control shRNA + SF). Overall, the data obtained demonstrated the great potential of PAMA114-co-PLAMA20/MYC shRNA nanosystems combined with low doses of SF for the treatment of HCC.

pH-responsive nanoparticles based on POEOMA-b-PDPA block copolymers for RNA encapsulation, protection and cell delivery.

The use of gene-based products, such as DNA or RNA, is increasingly being explored for various innovative therapies. However, the success of these strategies is highly dependent on the effective delivery of these biomolecules to target cells. Therefore, the development of pH-responsive nanoparticles comprises the creation of intelligent delivery systems with high therapeutic efficiency. In this work, the pH-responsiveness of the poly(2-(diisopropylamino)ethyl methacrylate)) (PDPA) block was investigated for the encapsulation and delivery of small RNAs (sRNA) to cancer cells. The pH responsiveness was dependent on the protonation profile of the tertiary amines of PDPA, which directly affected the electrostatic interactions established with RNA. Thus, block copolymers based on poly(oligo(ethylene oxide) methyl ether methacrylate) (POEOMA) and PDPA, POEOMA-b-PDPA, were synthesized by supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP). The structure of the block copolymers was characterized by size exclusion chromatography and 1H NMR spectroscopy. The copolymers allowed effective complexation of model sRNAs and a pre-miRNA with efficiencies of about 89 % and 91 %, respectively. The characterization by dynamic light scattering revealed that these systems had sizes between 76 and 1375 nm. It was also found that the morphology of the polyplexes depended on the pH, since the preparation at a pH lower than the pKa of the copolymers resulted in spherical but polydisperse particles, while higher pH values resulted in nanoparticles with more homogeneous size, but altered morphology. Moreover, due to pH-responsiveness, it was achieved the release of RNA at pH higher than the pKa of the copolymers, while maintaining its integrity. The polyplexes also showed a high potential to protect RNA from RNases. The transfection of a lung cancer model (A549) and fibroblast cell lines showed that these polyplexes did not cause cell toxicity. In addition, the polyplexes enabled the effective transfection of the A549 cell line with pre-miRNA-29b and miRNA-29b, resulting in a decrease of expression levels of the target DNMT3B gene by approximately 51 % and 47 %, respectively. Overall, the POEOMA-b-PDPA copolymers proved to be a promising strategy for developing responsive delivery systems, that can play a critical role in some diseases, such as cancer, where pH varies between the intra and extracellular environments.

Replacing Harmful Flame Retardants with Biodegradable Starch-Based Materials in Polyethylene Formulations.

The addition of toxic flame retardants to commercially available polymers is often required for safety reasons due to the high flammability of these materials. In this work, the preparation and incorporation of efficient biodegradable starch-based flame retardants into a low-density polyethylene (LDPE) matrix was investigated. Thermoplastic starch was first obtained by plasticizing starch with glycerol/water or glycerol/water/choline phytate to obtain TPS-G and TPS-G-CPA, respectively. Various LDPE/TPS blends were prepared by means of melt blending using polyethylene graft maleic anhydride as a compatibilizer and by varying the content of TPS and a halogenated commercial flame retardant. By replacing 38% and 76% of the harmful commercial flame retardant with safe TPS-G-CPA and TPS-G, respectively, blends with promising fire behavior were obtained, while the limiting oxygen index (LOI ≈ 28%) remained the same. The presence of choline phytate improved both the charring ability and fire retardancy of starch and resulted in a 43% reduction in fire growth index compared to the blend with commercial flame retardant only, as confirmed by means of cone calorimetry. Standard UL 94 vertical tests showed that blends containing TPS exhibited dripping behavior (rated V2), while those with commercial flame retardant were rated V0. Overall, this work demonstrates the potential of starch as a natural flame retardant that could reduce the cost and increase the safety of polymer-based materials.

Nanotechnology-based techniques for hair follicle regeneration.

The hair follicle (HF) is a multicellular complex structure of the skin that contains a reservoir of multipotent stem cells. Traditional hair repair methods such as drug therapies, hair transplantation, and stem cell therapy have limitations. Advances in nanotechnology offer new approaches for HF regeneration, including controlled drug release and HF-specific targeting. Until recently, embryogenesis was thought to be the only mechanism for forming hair follicles. However, in recent years, the phenomenon of wound-induced hair neogenesis (WIHN) or de novo HF regeneration has gained attention as it can occur under certain conditions in wound beds. This review covers HF-specific targeting strategies, with particular emphasis on currently used nanotechnology-based strategies for both hair loss-related diseases and HF regeneration. HF regeneration is discussed in several modalities: modulation of the hair cycle, stimulation of progenitor cells and signaling pathways, tissue engineering, WIHN, and gene therapy. The HF has been identified as an ideal target for nanotechnology-based strategies for hair regeneration. However, some regulatory challenges may delay the development of HF regeneration nanotechnology based-strategies, which will be lastly discussed.

Facile Synthesis of Highly Stretchable, Tough, and Photodegradable Hydrogels.

Recently, highly stretchable and tough hydrogels that are photodegradable on-demand have been reported. Unfortunately, the preparation procedure is complex due to the hydrophobic nature of the photocrosslinkers. Herein, a simple method is reported to prepare photodegradable double-network (DN) hydrogels that exhibit high stretchability, toughness, and biocompatibility. Hydrophilic ortho-nitrobenzyl (ONB) crosslinkers incorporating different poly(ethylene glycol) (PEG) backbones (600, 1000, and 2000 g mol-1 ) are synthesized. These photodegradable DN hydrogels are prepared by the irreversible crosslinking of chains by using such ONB crosslinkers, and the reversible ionic crosslinking between sodium alginate and divalent cations (Ca2+ ). Remarkable mechanical properties are obtained by combining ionic and covalent crosslinking and their synergistic effect, and by reducing the length of the PEG backbone. The rapid on-demand degradation of these hydrogels is also demonstrated by using cytocompatible light wavelength (λ = 365 nm) that degrades the photosensitive ONB units. The authors have successfully used these hydrogels as skin-worn sensors for monitoring human respiration and physical activities. A combination of excellent mechanical properties, facile fabrication, and on-demand degradation holds promise for their application as the next generation of substrates or active sensors eco-friendly for bioelectronics, biosensors, wearable computing, and stretchable electronics.

In Vitro Evaluation of Biphasic Calcium Phosphate Scaffolds Derived from Cuttlefish Bone Coated with Poly(ester urea) for Bone Tissue Regeneration.

This study investigates the osteogenic differentiation of umbilical-cord-derived human mesenchymal stromal cells (hUC-MSCs) on biphasic calcium phosphate (BCP) scaffolds derived from cuttlefish bone doped with metal ions and coated with polymers. First, the in vitro cytocompatibility of the undoped and ion-doped (Sr2+, Mg2+ and/or Zn2+) BCP scaffolds was evaluated for 72 h using Live/Dead staining and viability assays. From these tests, the most promising composition was found to be the BCP scaffold doped with strontium (Sr2+), magnesium (Mg2+) and zinc (Zn2+) (BCP-6Sr2Mg2Zn). Then, samples from the BCP-6Sr2Mg2Zn were coated with poly(ԑ-caprolactone) (PCL) or poly(ester urea) (PEU). The results showed that hUC-MSCs can differentiate into osteoblasts, and hUC-MSCs seeded on the PEU-coated scaffolds proliferated well, adhered to the scaffold surfaces, and enhanced their differentiation capabilities without negative effects on cell proliferation under in vitro conditions. Overall, these results suggest that PEU-coated scaffolds are an alternative to PCL for use in bone regeneration, providing a suitable environment to maximally induce osteogenesis.

Copper-mediated controlled/"living" radical polymerization in polar solvents: insights into some relevant mechanistic aspects.

The field of transition-metal-mediated controlled/"living" radical polymerization (CLRP) has become the subject of intense discussion regarding the mechanism of this widely-used and versatile process. Most mechanistic analyses (atom transfer radical polymerization (ATRP) vs. single-electron transfer living radical polymerization (SET-LRP)) have been based on model experiments, which cannot correctly mimic the true reaction conditions. We present, for the first time, a determination of the [Cu(I)Br]/[L] (L=nitrogen-based chelating ligand) ratio and the extent of Cu(I)Br/L disproportionation during CLRP of methyl acrylate (MA) in dimethylsulfoxide (DMSO) with Cu(0) wire as a transition-metal catalyst source. The results suggest that Cu(0) acts as a supplemental activator and reducing agent of Cu(II)Br(2)/L to Cu(I)Br/L. More importantly, the Cu(I)Br/L species seem to be responsible for the activation of SET-LRP.

Application of vinyl polymer-based materials as nucleic acids carriers in cancer therapy.

Nucleic acid-based therapies have changed the paradigm of cancer treatment, where conventional treatment modalities still have several limitations in terms of efficacy and severe side effects. However, these biomolecules have a short half-life in vivo, requiring multiple administrations, resulting in severe suffering, discomfort, and poor patient compliance. In the early days of (nano)biotechnology, these problems caused concern in the medical community, but recently it has been recognized that these challenges can be overcome by developing innovative formulations. This review focuses on the use of vinyl polymer-based materials for the protection and delivery of nucleic acids in cancer. First, an overview of the properties of nucleic acids and their versatility as drugs is provided. Then, key information on the achievements to date, the most effective delivery methods, and the evaluation of functionalization approaches (stimulatory strategies) are critically discussed to highlight the importance of vinyl polymers in the new cancer treatment approaches. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures.

Dual electrochemical and chemical control in atom transfer radical polymerization with copper electrodes.

In Atom Transfer Radical Polymerization (ATRP), Cu0 acts as a supplemental activator and reducing agent (SARA ATRP) by activating alkyl halides and (re)generating the CuI activator through a comproportionation reaction, respectively. Cu0 is also an unexplored, exciting metal that can act as a cathode in electrochemically mediated ATRP (eATRP). Contrary to conventional inert electrodes, a Cu cathode can trigger a dual catalyst regeneration, simultaneously driven by electrochemistry and comproportionation, if a free ligand is present in solution. The dual regeneration explored herein allowed for introducing the concept of pulsed galvanostatic electrolysis (PGE) in eATRP. During a PGE, the process alternates between a period of constant current electrolysis and a period with no applied current in which polymerization continues via SARA ATRP. The introduction of no electrolysis periods without compromising the overall polymerization rate and control is very attractive, if large current densities are needed. Moreover, it permits a drastic charge saving, which is of unique value for a future scale-up, as electrochemistry coupled to SARA ATRP saves energy, and shortens the equipment usage.