Biodegradable and electrically conducting polymers for biomedical applications
Introduction
The past two decades have witnessed a significant advance in the biodegradable polymeric material field. Due to their excellent biocompatibility, biodegradable polymers have been widely used in biomedical applications, including surgical sutures, bone fixation devices, vascular grafts, artificial skin, drug delivery systems, gene delivery systems, diagnostic applications and tissue engineering [1], [2], [3]. Tissue engineering, also called regenerative medicine, is an interdisciplinary field involving knowledge of medicine, biology, engineering and materials science. Tissue engineering aims to improve or replace failing or malfunctioning body tissue by combining scaffolds, cells and bioactive molecules [4], [5], [6]. The scaffolds are designed to be a temporary support for cells and to promote cell differentiation and proliferation toward the formation of the desired new tissue. Scaffolds have to combine several functions including biocompatibility with the host tissue, controlled biodegradability with non-toxic degradation products, adequate porosity for the transportation of small molecules, optimal mechanical strength and controllability during cell growth, implantation and sterilization [7], [8], [9]. The biomaterials used for scaffolding should also totally degrade when the support is no longer needed. Due to their degradability and mechanical properties, natural polymers such as chitosan, gelatin, heparin, and collagen have been widely used for the fabrication of scaffolds for tissue engineering [9], [10], [11]. However, natural polymers may suffer quality variation from batch to batch and have an undesirable immune response. The most widely used synthetic scaffolding materials are aliphatic polyesters such as polylactide, polycaprolactone, polyglycolide and their copolymers, owing to their excellent non-toxicity, biocompatibility, biodegradability, and good mechanical properties [12], [13], [14]. Nevertheless, the poor hydrophilicity of aliphatic polyesters does not promote cell attachment on their surfaces, and the surfaces of polyesters also lack natural sites for covalent bonding of cell-recognition signal molecules to induce cell attachment and regulate the cell behavior, and this limits the application of polyesters in tissue engineering [15], [16].
Conducting polymers (CPs) as a novel generation of organic materials were first synthesized in the mid-1970s. CPs have electrical and optical properties similar to those of metals and inorganic semiconductors, but they also possess attractive properties similar to those of common polymers, such as ease of synthesis and good processability compared to metals [17], [18]. CPs are widely used in the microelectronics industry, including battery technology, photovoltaic devices, light-emitting diodes, and electrochromic displays [19], [20], [21], and more recently also in biomedical applications [22], [23], [24], [25]. Research on CPs for biomedical applications expanded greatly in the 1980s when it was found that these materials were compatible with many biological molecules. Cell and tissue compatibility of conductive polymers such as polypyrrole (PPy) [26], [27], polyaniline (PANi) [28], [29], polythiophene [30] and their derivatives [31], [32], [33] were demonstrated both in vitro and in vivo. CPs have been used in various biomedical applications including neural probes [34], neural prostheses [35] and controlled release systems [36], [37], [38]. By the mid-1990s, CPs were also shown to tune cellular activities through electrical stimulation (conductivities from 10−4 to 9 S/cm) such as cell growth [39], [40], [41], [42] and cell migration [43] and this led to a considerable interest in conducting polymers and their derivatives for tissue engineering applications [33], [44], [45]. Many of these studies are related to nerve, bone, muscle, keratinocytes, fibroblasts, cardiac cells, and mesenchymal stem cells [46], [47], [48], [49], which are sensitive to electrical stimulation. This shows the importance of conducting polymers in tissue engineering, since the regulation of cellular behavior is crucial for the regeneration of damaged tissue [50], [51], [52]. However, there are practical problems when these conductive polymers are used in tissue engineering. The main drawbacks with the existing systems are poor polymer-cell interactions, the absence of cell interaction sites, hydrophobicity, poor solubility and processability, as well as uncontrollable mechanical properties [22], [53], [54], [55], [56]. Their inability to degrade is one of the greatest limitations for tissue engineering applications. Keeping conducting polymers in vivo for a long time may trigger an inflammatory response and the need for a second surgical procedure [57]. The synthesis of materials with both electroactive and degradable properties is highly desirable, and is still a challenge. This review focuses on the different fabrication and synthesis routes of degradable and electrically conducting polymers using both conducting polymers to form blends and composites as well as conducting oligomers to form degradable and conducting copolymers. The tissue engineering applications and the future trends of degradable and conducting polymers are also highlighted.
Section snippets
Blends and composites of degradable conductive polymers
To overcome the drawbacks such as poor mechanical properties, poor processability, hydrophobicity and non-degradability of CPs, polymer blends and composites based on conducting polymers such as PPy and PANi and degradable polymers such as polylactide (PLA) [58], [59], [60], polycaprolactone (PCL) [59], [61], [62], poly(lactide-co-glycolide) (PLGA) [63], polycaprolactone fumarate [64], [65], poly(lactide-co-polycaprolactone) (PLA-co-PCL) [48], polyurethane [66], chitosan [58], [67], [68],
Erodible and electrically conducting polymers
Although, the amount of PANi or PPy in the degradable and conducting blends or composites discussed above was minimized, eliminating to some extent the need for degradability; the small amounts of PANi or PPy introduced into the body through these materials are expected to stay in vivo. Therefore, the synthesis of completely degradable and electrically conducting polymers is still highly anticipated.
One strategy to synthesize degradable conducting polymers is to design erodible conducting
Linear degradable conducting polymers
Oligomers of pyrrole, thiophene [109], [110] and aniline [111], [112], [113] have well-defined structures, good solubility, high flexibility during synthesis and processing, and an electroactivity similar to that of their corresponding conducting polymers. In addition, the oligomers of pyrrole, thiophene and aniline would be consumed by macrophages, and subsequently cleared by the kidney [110], [114], [115], eliminating the need for surgical removal of the materials. New possibilities for the
Concluding remarks and outlook
Polymers exhibiting both conductivity and degradability represent a new class of biomaterials and dozens of different degradable and electrically conductive polymers (DECPs) have been synthesized during the past decade. Nevertheless, this library still needs to be expanded to meet the demands of specific applications.
One of the challenges of degradable and conducting polymers is the optimization of their conductivity. New DECPs that have a low content of the conducting species and still possess
Acknowledgments
The authors gratefully acknowledge the China Scholarship Council (CSC), the ERC Advanced Grant, PARADIGM (Grant agreement no: 246776) and The Royal Institute of Technology (KTH) for financial support of this work.
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