Smart and Multifunctional Materials Based on Electroactive Poly(vinylidene fluoride): Recent Advances and Opportunities in Sensors, Actuators, Energy, Environmental, and Biomedical Applications.

From scientific and technological points of view, poly(vinylidene fluoride), PVDF, is one of the most exciting polymers due to its overall physicochemical characteristics. This polymer can crystalize into five crystalline phases and can be processed in the form of films, fibers, membranes, and specific microstructures, being the physical properties controllable over a wide range through appropriate chemical modifications. Moreover, PVDF-based materials are characterized by excellent chemical, mechanical, thermal, and radiation resistance, and for their outstanding electroactive properties, including high dielectric, piezoelectric, pyroelectric, and ferroelectric response, being the best among polymer systems and thus noteworthy for an increasing number of technologies. This review summarizes and critically discusses the latest advances in PVDF and its copolymers, composites, and blends, including their main characteristics and processability, together with their tailorability and implementation in areas including sensors, actuators, energy harvesting and storage devices, environmental membranes, microfluidic, tissue engineering, and antimicrobial applications. The main conclusions, challenges and future trends concerning materials and application areas are also presented.

High Performance of Metallic Thin Films for Resistance Temperature Devices with Antimicrobial Properties.

Titanium-copper alloy films with stoichiometry given by Ti1-xCux were produced by magnetron co-sputtering technique and analyzed in order to explore the suitability of the films to be applied as resistive temperature sensors with antimicrobial properties. For that, the copper (Cu) amount in the films was varied by applying different DC currents to the source during the deposition in order to change the Cu concentration. As a result, the samples showed excellent thermoresistivity linearity and stability for temperatures in the range between room temperature to 110 °C. The sample concentration of Ti0.70Cu0.30 has better characteristics to act as RTD, especially the αTCR of 1990 ×10-6°C-1. The antimicrobial properties of the Ti1-xCux films were analyzed by exposing the films to the bacterias S. aureus and E. coli, and comparing them with bare Ti and Cu films that underwent the same protocol. The Ti1-xCux thin films showed bactericidal effects, by log10 reduction for both bacteria, irrespective of the Cu concentrations. As a test of concept, the selected sample was subjected to 160 h reacting to variations in ambient temperature, presenting results similar to a commercial temperature sensor. Therefore, these Ti1-xCux thin films become excellent antimicrobial candidates to act as temperature sensors in advanced coating systems.

Tuning Properties of Cerium Dioxide Nanoparticles by Surface Modification with Catecholate-type of Ligands.

Cerium dioxide (CeO2) finds applications in areas such as corrosion protection, solar cells, or catalysis, finding increasing applications in biomedicine. This work reports on surface-modified CeO2 particles in order to tune their applicability in the biomedical field. Stable aqueous CeO2 sol, consisting of 3-4 nm in size crystallites, was synthesized using forced hydrolysis. The coordination of catecholate-type of ligands (catechol, caffeic acid, tiron, and dopamine) to the surface-Ce atoms is followed with the appearance of absorption in the visible spectral range as a consequence of interfacial charge-transfer complex formation. The spectroscopic observations are complemented with the density functional theory calculations using a cluster model. The synthesized samples were characterized by X-ray diffraction analysis, transmission electron microscopy, and nitrogen adsorption-desorption isotherms. The ζ-potential measurements indicated that the stability of CeO2 sol is preserved upon surface modification. The pristine CeO2 nanoparticles (NPs) are nontoxic against pre-osteoblast cells in the entire studied concentration range (up to 1.5 mM). Hybrid CeO2 NPs, capped with dopamine or caffeic acid, display toxic behavior for concentrations ≥0.17 and 1.5 mM, respectively. On the other hand, surface-modified CeO2 NPs with catechol and tiron promote the proliferation of pre-osteoblast cells.

Magnetic Bioreactor for Magneto-, Mechano- and Electroactive Tissue Engineering Strategies.

Biomimetic bioreactor systems are increasingly being developed for tissue engineering applications, due to their ability to recreate the native cell/tissue microenvironment. Regarding bone-related diseases and considering the piezoelectric nature of bone, piezoelectric scaffolds electromechanically stimulated by a bioreactor, providing the stimuli to the cells, allows a biomimetic approach and thus, mimicking the required microenvironment for effective growth and differentiation of bone cells. In this work, a bioreactor has been designed and built allowing to magnetically stimulate magnetoelectric scaffolds and therefore provide mechanical and electrical stimuli to the cells through magnetomechanical or magnetoelectrical effects, depending on the piezoelectric nature of the scaffold. While mechanical bioreactors need direct application of the stimuli on the scaffolds, the herein proposed magnetic bioreactors allow for a remote stimulation without direct contact with the material. Thus, the stimuli application (23 mT at a frequency of 0.3 Hz) to cells seeded on the magnetoelectric, leads to an increase in cell viability of almost 30% with respect to cell culture under static conditions. This could be valuable to mimic what occurs in the human body and for application in immobilized patients. Thus, special emphasis has been placed on the control, design and modeling parameters governing the bioreactor as well as its functional mechanism.

Bottom-up Layer-by-Layer Assembling of Antibacterial Freestanding Nanobiocomposite Films.

In this study, freestanding nanobiocomposite films were obtained by the sequential deposition of biopolymer-capped silver nanoparticles (AgNPs) and hyaluronic acid (HA). At first, dispersions of AgNPs decorated with chitosan (CS) or aminocellulose (AC) were synthesized by applying high intensity ultrasound. These polycationic nanoentities were layer-by-layer assembled with the HA polyanion to generate stable 3D supramolecular constructs, where the biopolymer-capped AgNPs play the dual role of active agent and structural element. SEM images of the assemblies revealed gradual increase of thickness with the number of deposited bilayers. The composites of ≥50 bilayers were safe to human cells and demonstrated 100% antibacterial activity against Staphylococcus aureus and Escherichia coli. Moreover, the films containing CSAgNPs brought about the total prevention of biofilm formation reducing the cells surface adherence by up to 6 logs. Such nanobiocomposites could serve as an effective barrier to control bacterial growth on injured skin, burns, and chronic wounds.

Escherichia coli and Pseudomonas aeruginosa eradication by nano-penicillin G.

The transformation of penicillin G into nano/micro-sized spheres (nanopenicillin) using sonochemical technology was explored as a novel tool for the eradication of Gram-negative bacteria and their biofilms. Known by its effectiveness only against Gram-positive microorganisms, the penicillin G spherization boosted the inhibition of the Gram-negative Pseudomonas aeruginosa 10-fold (from 0.3 to 3.0 log-reduction) and additionally induced 1.2 log-reduction of Escherichia coli growth. The efficient penetration of the spheres within a Langmuir monolayer sustained the theory that nanopenicillin is able to cross the membrane and reach the periplasmic space in Gram-negative bacteria where they inhibit the ß-lactam targets: the transferases that build the bacteria cell wall. Moreover, it considerably suppressed the growth of both bacterial biofilms on a medically relevant polystyrene surface, leaving majority of the adhered cells dead compared to the treatment with the non-processed penicillin G. Importantly, nanopenicillin was found innocuous towards human fibroblasts at the antibacterial-effective concentrations.

Enzyme multilayer coatings inhibit Pseudomonas aeruginosa biofilm formation on urinary catheters.

Bacteria use a signaling mechanism called quorum sensing (QS) to form complex communities of surface-attached cells known as biofilms. This protective mode of growth allows them to resist antibiotic treatment and originates the majority of hospital-acquired infections. Emerging alternatives to control biofilm-associated infections and multidrug resistance development interfere with bacterial QS pathways, exerting less selective pressure on bacterial population. In this study, biologically stable coatings comprising the QS disrupting enzyme acylase were built on silicone urinary catheters using a layer-by-layer technique. This was achieved by the alternate deposition of negatively charged enzyme and positively charged polyethylenimine. The acylase-coated catheters efficiently quenched the QS in the biosensor strain Chromobacterium violaceum CECT 5999, demonstrated by approximately 50% inhibition of violacein production. These enzyme multilayer coatings significantly reduced the Pseudomonas aeruginosa ATCC 10145 biofilm formation under static and dynamic conditions in an in vitro catheterized bladder model. The quorum quenching enzyme coatings did not affect the viability of the human fibroblasts (BJ-5ta) over 7 days, corresponding to the extended useful life of urinary catheters. Such enzyme-based approach could be an alternative to the conventional antibiotic treatment for prevention of biofilm-associated urinary tract infections.

Sonochemically processed cationic nanocapsules: efficient antimicrobials with membrane disturbing capacity.

Bacterial-mediated diseases are a major healthcare concern worldwide due to the rapid spread of antibiotic-resistant bacteria. One strategy to manage the bacterial infections while avoiding the emergence of resistant strains implies specific targeting and disruption of bacteria membranes. This work evaluates the potential of nanostructured biopolymer derivatives, nanocapsules (NCs), to disrupt the bacteria cell walls and effectively kill planktonic microorganisms. Two biopolymers, chitosan and cellulose, were chemically modified to synthesize derivatives with improved cationic character (thiolated chitosan and aminocellulose) prior to their processing into nanocapsules via a one-step sonochemical process. The interactions of NCs, displaying an average size of around 250 nm, with bacteria membrane were evaluated using two membrane models: Langmuir monolayers and liposome bilayers composed of a l-α-phosphatidylglycerol phospholipid extracted from Escherichia coli. NCs possessed improved membrane disturbing capacity in comparison to the nonprocessed biopolymer derivatives, by drastically increasing the monolayer fluidity and inducing more than 50% leakage of a dye inserted in the bilayered liposomes. In addition, membrane disturbance was directly proportional to the NCs cationic charge. Whereas evidence showed that thiolated chitosan and aminocellulose interacted with the bacteria membrane through a "carpet model", the NCs were found to induce larger surface defects and high local perturbance through a "detergent model". Importantly, the degree of disruption caused by the biopolymer derivatives and NCs correlated well with the antimicrobial capacity against Escherichia coli, selectively killing bacteria cells without imparting toxicity to human fibroblasts.

A 3D-Printed Portable UV and Visible Photoreactor for Water Purification and Disinfection Experiments.

Water scarcity and contamination are urgent issues to be addressed. In this context, different materials, techniques, and devices are being developed to mitigate contemporary and forthcoming water constraints. Photocatalysis-based approaches are suitable strategies to address water contamination by degrading contaminants and eliminating microbes. Photoreactors are usually designed to perform photocatalysis in a scalable and standardised way. Few or none have been developed to combine these characteristics with portability, flexibility, and cost effectiveness. This study reports on designing and producing a portable (490 g), low-cost, and multifunctional photoreactor that includes adjustable radiation intensity and two types of wavelengths (UV-A and visible), including combined agitation in a compact mechanism produced through 3D printing technology. The mechanical, electrical, and optical subsystems were designed and assembled into a robust device. It is shown that it is possible to apply radiations that can reach 65 mW/cm2 and 110 mW/cm2 using the installed visible and UV LEDs and apply mechanical agitation up to 200 rpm, all under a ventilated system. Regarding functionality, the photoreactor proof of concept indicated the ability to degrade ~80% and 30% ciprofloxacin under UV and visible irradiation of TiO2 and Ag/TiO2 nanoparticles. The device also showed the ability to eliminate E. coli bacteria, recurring to radiation set-ups and nanoparticles. Therefore, the originally designed and constructed photoreactor concept was characterised and functionally validated as an exciting and flexible device for lab-scaled or outdoor experiments, assuring standardised and comparable results.

Accuracy of Silicone Impressions and Stone Models Using Two Laboratory Scanners: A 3D Evaluation.

PURPOSE: To evaluate the in vitro accuracy of impressions obtained with two silicone and corresponding stone models using two laboratory scanners. MATERIALS AND METHODS: A master model with synthetic resin teeth with two single-unit crown preparations was created and scanned using a 12-megapixel scanner. Five conventional impressions of the physical model were prepared with different silicone impression systems (Zhermack and Coltene) using the double-mix technique and poured with gypsum. The impressions and stone models obtained were scanned using two extraoral scanning systems (Identica T500, Medit; S600 ARTI, Zirkonzahn). All best-fit superimpositions of the teeth areas were conducted between the master model and the scans of the impressions and models obtained with the two scanners. A P < .05 level was considered significant. RESULTS: The Identica T500 Medit scanner showed an accuracy of 102.34 (89.67, 115.01) µm for Coltene silicone and 79.51 (67.82, 91.21) µm for Zhermack silicone, while the S600 ARTI Zirkonzhan scanner presented 110.79 (98.24, 123.33) µm and 91.91 (81.29, 102.54) µm, respectively, with significant differences between scanners for Zhermack silicone (P = .008) and for the corresponding stone models (P = .002). Zhermack silicone presented overall discrepancies lower than Coltene silicone, with statistically significant differences in both scanners analyzed (P < .001; P = .017). However, the discrepancies found were within clinically acceptable values. With the Zirkonzahn scanner, discrepancies found in the Zhermack impressions were lower than in the corresponding stone models (P < .001). CONCLUSIONS: The direct digitization of silicone impressions with laboratory scanners presented comparable results to conventional techniques with stone models.

Designing antimicrobial biomembranes via clustering amino-modified cellulose nanocrystals on silk fibroin ß-sheets.

The continuous rising of infections caused by multidrug-resistant pathogens is becoming a global healthcare concern. Developing new bio-based materials with unique chemical and structural features that allow efficient interaction with bacteria is thus important for fighting this phenomenon. To address this issue, we report an antimicrobial biomaterial that results from clustering local facial amphiphilicity from amino-modified cellulose on silk fibroin ß-sheets, by simply blending the two components through casting technology. A simple but effective method for creating a membrane that is antibacterial and non-cytotoxic. Amino-modified cellulose nanocrystals (CNC-NH2) were mixed with proteinaceous silk fibroin (SF) which resulted in a material with improved crystallinity, higher ß-sheet content, and exposed amino-groups at its surface features, proven by Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS), that does not occur when the components are individually assembled. The resulting material possesses important antibacterial activity inducing >3 CFU log10 reduction of Escherichia coli and Staphylococcus epidermidis, while the pristine membranes show no antibacterial effect. The chemical interactions occurring between SF and CNC-NH2 during casting, exposing the amino moieties at the surface of the material, are proposed as the main reason for this antimicrobial activity. Importantly, the membranes are non-cytotoxic, showing their potential to be used as a new bioinspired material with intrinsic antibacterial activity for biomedical applications. Those may include coatings for medical devices for the control of healthcare-associated infections, with no need for including external antimicrobial agents in the material.

Molecular modeling of hair keratin/peptide complex: Using MM-PBSA calculations to describe experimental binding results.

Molecular dynamics simulations of a keratin/peptide complex have been conducted to predict the binding affinity of four different peptides toward human hair. Free energy calculations on the peptides' interaction with the keratin model demonstrated that electrostatic interactions are believed to be the main driving force stabilizing the complex. The molecular mechanics-Poisson-Boltzmann surface area methodology used for the free energy calculations demonstrated that the dielectric constant in the protein's interior plays a major role in the free energy calculations, and the only way to obtain accordance between the free energy calculations and the experimental binding results was to use the average dielectric constant.

Two- and three-dimensional piezoelectric scaffolds for bone tissue engineering.

The incidence of bone disorders worldwide is increasing. For this reason, new and more effective strategies for bone repair are needed. The most common strategy used for cell regeneration relies in biochemical stimulation while biophysical stimulation using mechanical, and electrical cues is a promising, however, still under-investigated field. This work reports on the development of piezoelectric 2D and 3D porous scaffolds for bone tissue regeneration strategies. While the porous scaffolds mimic the bone's structure, the piezoelectric activity of the scaffolds mimics the bone mechano-electric microenvironment. The piezoelectric activity is related to the electroactive ß-phase of poly(vinylidene fluoride) (PVDF) in the scaffolds and was dynamically stimulated by cell culture in a custom-made mechanical bioreactor. These two factors combined provide an effective biomimetic environment for the proliferation of preosteoblasts. The electromechanically-responsive scaffolds are found to promote the enhancement of proliferation rate of MC3T3-E1 osteoblastic cells in about 20 % as well as an improved adhesion and proliferation over the materials, mainly when dynamically stimulated. These results prove that local piezoelectric effect, as the one existing in bone tissue, allows effective cell proliferation, which could be further translated in more efficient strategies for bone tissue regeneration.

Flexible TiCux Thin Films with Dual Antimicrobial and Piezoresistive Characteristics.

The eradication of microorganisms from high traffic surfaces to prevent either viral or bacterial infections represents an urgent need, mainly in the scope of the present pandemic scenario. In this context, this work explores the dual functionality of titanium-copper thin films as pressure elements with antimicrobial properties, aiming for the implementation of touch and sensing capabilities in high traffic surfaces. Copper was employed as the antibacterial agent within a titanium matrix. The film's geometry and deposition parameters were varied in order to optimize antimicrobial and piezoresistive response. A considerable antimicrobial response has been obtained, increasing the copper amount (from 23 to 63 at. %) in the titanium matrix, leading to an outstanding 8 log10 CFU bacterial reduction in the case of Escherichia coli. Moreover, for the same amount of copper, the piezoresistive sensibility of the thin films increases up to a maximum gauge factor of 5.18 ± 0.09, which indicates an adequate electromechanical behavior for sensing applications. Our findings demonstrate the best combined antimicrobial and piezoresistive characteristics for the films with a Cu content of 63 at. %, indicating a potential use of these films for electromechanical sensor applications.

Exploring electroactive microenvironments in polymer-based nanocomposites to sensitize bacterial cells to low-dose embedded silver nanoparticles.

The search for alternative antimicrobial strategies capable of avoiding resistance mechanisms in bacteria are highly needed due to the alarming emergence of antimicrobial resistance. The application of physical stimuli as a mean of sensitizing bacteria for the action of antimicrobials on otherwise resistant bacteria or by allowing the action of low quantity of antimicrobials may be seen as a breakthrough for such purpose. This work proposes the development of antibacterial nanocomposites using the synergy between the electrically active microenvironments, created by a piezoelectric polymer (poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE)), with green-synthesized silver nanoparticles (AgNPs). The electrical microenvironment is generated via mechanical stimulation of piezoelectric PVDF-TrFE/AgNPs films using a lab-made mechanical bioreactor. The generated material's electrical response further translates to bacterial cells, namely Escherichia coli and Staphylococcus epidermidis which in combination with AgNPs and the specific morphological features of the material induce important antibacterial and antibiofilm activity. Both porous and non-porous PVDF composites have shown antibacterial characteristics when stimulated at a mechanical frequency of 4 Hz being the effect boosted when AgNPs were incorporated in the nanocomposite, reducing in more than 80% the S. epidermidis bacterial growth in planktonic and biofilm form. The electroactive environments sensitize the bacteria allowing the action of a low dose of AgNPs (1.69% (w/w)). Importantly, the material did not compromise the viability of mammalian cells, thus being considered biocompatible. The piezoelectric stimulation of PVDF-based polymeric films may represent a breakthrough in the development of antibacterial coatings for devices used at hospital setting, taking advantage on the use of mechanical stimuli (pressure/touch) to exert antibacterial and antibiofilm activity. STATEMENT OF SIGNIFICANCE: The application of physical methods in alternative to the common chemical ones is seen as a breakthrough for avoiding the emergence of antimicrobial resistance. Antimicrobial strategies that take advantage on the capability of bacteria to sense physical stimuli such as mechanical and electrical cues are scarce. Electroactive nanocomposites comprised of poly(vinylidene fluoride-co-trifluoroethylene (PVDF-TrFE) and green-synthesized silver nanoparticles (AgNPs) were developed to obtain material able to inhibit the colonization of microorganisms. By applying a mechanical stimuli to the nanocomposite, which ultimately mimics movements such as walking or touching, an antimicrobial effect is obtained, resulting from the synergy between the electroactive microenvironments created on the surface of the material and the AgNPs. Such environments sensitize the bacteria to low doses of antimicrobials.

Influence of glucose, sucrose, and dextran coatings on the stability and toxicity of silver nanoparticles.

Aqueous colloids, consisting of 15-30 nm-sized silver nanoparticles (Ag NPs), were prepared using the reducing and stabilizing abilities of glucose, sucrose, and dextran. The long-term stability of coated Ag NPs increases from glucose over sucrose to dextran, i.e., with the increase of the molecular weight of carbohydrate molecules. The density functional theory (DFT) calculations of the partial atomic (Mulliken) charges and adsorption energies are applied to explain the enhanced stability of coated Ag NPs. All coated Ag NPs have a significantly broader concentration range of nontoxic behavior toward pre-osteoblast cells than bare Ag NPs prepared using sodium borohydride. The carbohydrate-coated Ag NPs display the same level of toxic ability against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria as bare Ag NPs. The differences in toxicity mechanism of the coated and bare Ag NPs are a consequence of the absence and presence of co-occurring Ag+ ions in examined dispersion, respectively.

Ionic Liquids as Biocompatible Antibacterial Agents: A Case Study on Structure-Related Bioactivity on Escherichia coli.

The potential of ionic liquids (ILs) to be used as antimicrobial agents for biomedical applications has been hindered by the fact that most of them are cytotoxic toward mammalian cells. Understanding the mechanism of bacterial and mammalian cellular damage of ILs is key to their safety design. In this work, we evaluate the antimicrobial activity and mode of action of several ILs with varying anions and cations toward the clinically relevant Gram-negative Escherichia coli. Langmuir monolayer technique was used to evaluate if the IL's mode of action was related to the bacterial cell membrane interaction for an effective E. coli killing. 1-Decyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide [DMIM][TFSI] and trihexyltetradecyl phosphonium bis(trifluoromethylsulfonyl) imide [P6,6,6,14][TFSI] were surface-active and induced bacterial cell lysis, through a membrane-disruption phenomenon on bacteria, in a mechanism that was clearly related to the long alkyl chains of the cation. 1-Ethyl-3-methylimidazolium hydrogen sulfate [EMIM][HSO4] was highly antimicrobial toward E. coli and found suitable for biological applications since it was harmless to mammalian cells at most of the tested concentrations. The results suggest that the imidazolium cation of the ILs is mostly responsible not only for their antimicrobial activity but also for their cytotoxicity, and the inclusion of different anions may tailor the ILs' biocompatibility without losing the capacity to kill bacteria, as is the case of [EMIM][HSO4]. Importantly, this IL was found to be highly antimicrobial even when incorporated in a polymeric matrix.

Protein disulphide isomerase-assisted functionalization of keratin-based matrices.

In living systems, protein disulphide isomerase (PDI, EC 5.3.4.1) regulates the formation of new disulphide bonds in proteins (oxidase activity) and catalyzes the rearrangement of non-native disulphide bonds (isomerase activity), leading proteins towards their native configuration. In this study, PDI was used to attach cysteine-containing compounds (CCCs) onto hair, to enhance compound migration within hair fibre and to trigger protein release. A fluorescent (5(6)-TAMRA)-labelled keratin peptide was incorporated into hair by using PDI. Similarly, PDI promoted the grafting of a cysteine-functionalized dye onto wool, as suggested by matrix-assisted laser desorption and ionization time-of-flight results. These reactions were thought to involve oxidation of disulphide bonds between CCCs and wool or hair cysteine residues, catalyzed by the oxidized PDI active site. On the other hand, PDI was demonstrated to enhance the migration of a disulphide bond-functionalized dye within the keratin matrix and trigger the release of RNase A from wool fibres' surface. These observations may indicate that an isomerisation reaction occurred, catalyzed by the reduced PDI active site, to achieve the thiol-disulphide exchange, i.e. the rearrangement of disulphide bonds between CCCs and keratin. The present communication aims to highlight promising biotechnological applications of PDI, derived from its almost unique properties within the isomerase family.

Electroactive Smart Materials: Novel Tools for Tailoring Bacteria Behavior and Fight Antimicrobial Resistance.

Despite being very simple organisms, bacteria possess an outstanding ability to adapt to different environments. Their long evolutionary history, being exposed to vastly different physicochemical surroundings, allowed them to detect and respond to a wide range of signals including biochemical, mechanical, electrical, and magnetic ones. Taking into consideration their adapting mechanisms, it is expected that novel materials able to provide bacteria with specific stimuli in a biomimetic context may tailor their behavior and make them suitable for specific applications in terms of anti-microbial and pro-microbial approaches. This review maintains that electroactive smart materials will be a future approach to be explored in microbiology to obtain novel strategies for fighting the emergence of live threatening antibiotic resistance.

Bioinspired Three-Dimensional Magnetoactive Scaffolds for Bone Tissue Engineering.

Bone tissue repair strategies are gaining increasing relevance due to the growing incidence of bone disorders worldwide. Biochemical stimulation is the most commonly used strategy for cell regeneration, while the application of physical cues, including magnetic, mechanical, or electrical fields, is a promising, however, scarcely investigated field. This work reports on novel magnetoactive three-dimensional (3D) porous scaffolds suitable for effective proliferation of osteoblasts in a biomimetic microenvironment. This physically active microenvironment is developed through the bone-mimicking structure of the scaffold combined with the physical stimuli provided by a magnetic custom-made bioreactor on a magnetoresponsive scaffold. Scaffolds are obtained through the development of nanocomposites comprised of a piezoelectric polymer, poly(vinylidene fluoride) (PVDF), and magnetostrictive particles of CoFe2O4, using a solvent casting method guided by the overlapping of nylon template structures with three different fiber diameter sizes (60, 80, and 120 µm), thus generating 3D scaffolds with different pore sizes. The magnetoactive composites show a structure very similar to trabecular bone with pore sizes that range from 5 to 20 µm, owing to the inherent process of crystallization of PVDF with the nanoparticles (NPs), interconnected with bigger pores, formed after removing the nylon templates. It is found that the materials crystallize in the electroactive ß-phase of PVDF and promote the proliferation of preosteoblasts through the application of magnetic stimuli. This phenomenon is attributed to both local magnetomechanical and magnetoelectric response of the scaffolds, which induce a proper cellular mechano- and electro-transduction process.