materials Review Electroactive Smart Polymers for Biomedical Applications Humberto Palza 1,2,*, Paula Andrea Zapata 3 and Carolina Angulo-Pineda 1 1 Departamento de Ingeniería Química, Biotecnología y Materiales, Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile, 8370456 Santiago, Chile; [email protected] 2 Millenium Nuclei in Soft Smart Mechanical Metamaterials, Universidad de Chile, 8370456 Santiago, Chile 3 Grupo de Polímeros, Facultad de Química y Biología, Universidad de Santiago de Chile, 8350709 Santiago, Chile; [email protected] * Correspondence: [email protected]; Tel.: +56-229-784-085 Received: 6 December 2018; Accepted: 9 January 2019; Published: 16 January 2019 Abstract: The flexibility in polymer properties has allowed the development of a broad range of materials with electroactivity, such as intrinsically conductive conjugated polymers, percolated conductive composites, and ionic conductive hydrogels. These smart electroactive polymers can be designed to respond rationally under an electric stimulus, triggering outstanding properties suitable for biomedical applications. This review presents a general overview of the potential applications of these electroactive smart polymers in the field of tissue engineering and biomaterials. In particular, details about the ability of these electroactive polymers to: (1) stimulate cells in the context of tissue engineering by providing electrical current; (2) mimic muscles by converting electric energy into mechanical energy through an electromechanical response; (3) deliver drugs by changing their internal configuration under an electrical stimulus; and (4) have antimicrobial behavior due to the conduction of electricity, are discussed. Keywords: Electrically conductive polymers; Electroactive biomaterials; Electrical stimulation; Smart composites; Bioelectric effect; Drug delivery; Artificial muscle 1. Introduction Polymers have emerged in recent decades as one of the most promising materials in biomedical applications due to their high biocompatibility and degradation/absorption in physiological media [1]. Another key characteristic of polymers is their flexibility in terms of properties and functionalities, allowing their development from bioactive hydrogels to biodegradable thermoplastic polymers [2,3]. The polymer flexibility also includes a broad range of processing techniques, such as: extrusion [4], electro-spinning [5,6], 3D printing [7–9], microfluidity [10], and casting [11], among others [5]. Remarkably, by adding/embedding nanoparticles into a polymer matrix, novel nanocomposites can be developed further extending the range of properties and functionalities of polymers. For these reasons, polymers are extensively studied today for tissue engineering [12,13], wound healing [14], artificial muscles [15], and drug delivery [16], among other bio-applications [17]. Of recent interest in polymer science is the development of smart materials with a rationally designed stimulus/response behavior. In this context, electroactive smart polymer materials are stressed because of their ability to transfer electrons/ions under a specific electric field, having multiple applications in several engineering areas, such as soft robots and sensors [18,19]. The advantages of an electric field as external stimulus, compared to others, is related to the availability of equipment that allows precise control in terms of the current magnitude, the duration of electric pulses, intervals between pulses, etc. However, compared to other functional/smart polymer systems, electroactive Materials 2019, 12, 277; doi:10.3390/ma12020277 www.mdpi.com/journal/materials Materials 2019, 12, 277 2 of 24 smartMaterials polymers 2018, 11, x have FOR PEER been REVIEW less studied for biomedical applications, despite their multiple applications2 of 24 in tissue engineering [20–22]. For instance, these electroactive biomaterials can be applied to obtain multiple applications in tissue engineering [20–22]. For instance, these electroactive biomaterials can adhesion and proliferation of human cells, accelerating the process of regeneration in muscles, organs be applied to obtain adhesion and proliferation of human cells, accelerating the process of andregeneration bones [23– in26 muscles,]. They can organs also and be used bones for [23–26]. smart drugThey deliverycan also orbe asused artificial for smart muscle drug systems, delivery both or triggeredas artificial by electricmuscle systems, stimuli. Evenboth lesstriggered studied by iselectric the development stimuli. Even of less biocidal studied materials is the development based on their electricof biocidal conductivity materials despite based on that their today electric any conduc biomaterialtivity useddespite in tissuethat today engineering any biomaterial must not used only in be biocompatibletissue engineering in the must response not only of the be biocompatible host (patient) butin the also resp activeonse inof avoidingthe host (patient) the adhesion but also of bacteriaactive orin the avoiding formation the of adhesion biofilms on of its bacteria surface. or Based the onform theation bactericidal of biofilms effect ofon electrical its surfa stimulationce. Based (ES),on novelthe bactericidal electroactive e materials can be produced with the ability to prevent the formation of biofilms and future bacterial infections in the host. Therefore, a polymer able to deliver ES can merge the requirements needed for any biomaterial designed for tissue engineering purposes: to promote cellular adhesion and proliferation while avoiding biofilm formation through a bactericidal effect (see Figure1). FigureFigure 1. 1.Relationship Relationship betweenbetween electroactive biomaterials and and human human and and bacterial bacterial cells cells in in the the context context ofof tissue tissue engineering. engineering. InIn this this review, review, we providewe provide a general a general overview overview of the potential of the potential of electroactive of electroactive polymer biomaterials polymer consideredbiomaterials as aconsidered new generation as a new of smart generation systems of ablesmart to respondsystems specificallyable to respond to an specifically electric field to in an the contextelectric of field biomedical in the context applications. of biomedical These smartapplications. systems These range smart from polymerssystems range delivering from polymers an electric signaldelivering to polymers an electric changing signal someto polymers properties changing under some an electric properties stimulus under [27 an]. electric The review stimulus focuses [27]. on theThe capacity review offocuses these on electroactive the capacity polymers of these electroact to stimulate:ive polymers (1) cells into thestimulate: context (1) of cells tissue in the engineering; context (2)of antissue electromechanical engineering; (2) an response electromechanical for artificial respon muscles;se for (3) artificial drug delivery;muscles; (3) and drug (4) delivery; antimicrobial and mechanisms.(4) antimicrobial From mechanisms. a material point From of view,a material the electroactive point of view, polymers the electroactive include intrinsically polymers conductive include polymers,intrinsically percolated conductive conductive polymers, polymer percolated nanocomposites, conductive and polymer ionic conductive nanocomposites, hydrogels. and A generalionic overviewconductive of hydrogels. this review A is general summarized overview in Figureof this2 review. For further is summarized details about in Figure one or2. moreFor further of the above-mentioneddetails about one electroactive or more of propertiesthe above-mentioned or polymers, electroactive there are several properties excellent or polymers, reviews (for there instance, are seeseveral references excellent [17, 21reviews,27–33 (for]) in instance, which specific see references[17,21,27–33]) information can be obtained in which for specific a deeper information understanding can ofbe an obtained application. for a deeper understanding of an application. Materials 2019, 12, 277 3 of 24 Materials 2018, 11, x FOR PEER REVIEW 3 of 24 Figure 2. A general overview of electroactive polymers. The mechanism for the specific response to anFigure electric 2. A stimulus general canoverview be through of electroactive ionic or electric polymers. conduction. The mechanism These mechanisms for the specific can trigger response either to aan direct electric electric stimulus current can tobe the through material ionic and or theelectr mediumic conduction. producing These cell mechan stimulation,isms can or antimicrobialtrigger either behaviora direct electric or a change current in some to the polymer material properties, and the me producingdium producing an electromechanical cell stimulation, behavior or antimicrobial and specific drugbehavior delivery. or a change in some polymer properties, producing an electromechanical behavior and specific drug delivery. 2. Electroactive Conductive Polymers 2. Electroactive Conductive Polymers Electroactive polymers can be classified according to the mechanism of conduction in ionic conductiveElectroactive polymers polymers and electric can conductivebe classified polymers. according The to latter the aremechanism further classified of conduction as intrinsic in ionic and extrinsic,conductive based polymers on their and mechanism electric conductive of electron polymers. conduction. The While latter ionic are conductivefurther classified polymers as intrinsic present conductivitiesand