Elsevier

Progress in Polymer Science

Volume 38, Issue 9, September 2013, Pages 1263-1286
Progress in Polymer Science

Biodegradable and electrically conducting polymers for biomedical applications

https://doi.org/10.1016/j.progpolymsci.2013.06.003Get rights and content

Abstract

Conducting polymers have been widely used in biomedical applications such as biosensors and tissue engineering but their non-degradability still poses a limitation. Therefore, great attention has been directed toward the recently developed degradable and electrically conductive polymers (DECPs). The different strategies for synthesis of degradable and conducting polymers containing conducting oligomers are summarized and discussed here as well as the influence of different macromolecular architectures such as linear, star-shaped, hyperbranched and cross-linked DECPs. Blends and composites of biodegradable and conductive polymers are also discussed. The developing trends and challenges with the design of DECPs are also presented.

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.

References (184)

  • R.A. Green et al.

    Impact of co-incorporating laminin peptide dopants and neurotrophic growth factors on conducting polymer properties

    Acta Biomaterials

    (2010)
  • P. Humpolicek et al.

    Biocompatibility of polyaniline

    Synthetic Metals

    (2012)
  • C.H. Wang et al.

    In-vivo tissue response to polyaniline

    Synthetic Metals

    (1999)
  • D.H. Kim et al.

    Conducting polymers on hydrogel-coated neural electrode provide sensitive neural recordings in auditory cortex

    Acta Biomaterials

    (2010)
  • X.Y. Cui et al.

    In vivo studies of polypyrrole/peptide coated neural probes

    Biomaterials

    (2003)
  • P.M. George et al.

    Fabrication and biocompatibility of polypyrrole implants suitable for neural prosthetics

    Biomaterials

    (2005)
  • D. Svirskis et al.

    Electrochemically controlled drug delivery based on intrinsically conducting polymers

    Journal of Controlled Release

    (2010)
  • R. Wadhwa et al.

    Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode

    Journal of Controlled Release

    (2006)
  • J.E. Collazos-Castro et al.

    Bioelectrochemical control of neural cell development on conducting polymers

    Biomaterials

    (2010)
  • G.X. Shi et al.

    The regulation of cell functions electrically using biodegradable polypyrrole-polylactide conductors

    Biomaterials

    (2008)
  • R.A. Green et al.

    Conducting polymers for neural interfaces: challenges in developing an effective long-term implant

    Biomaterials

    (2008)
  • G.X. Shi et al.

    A novel electrically conductive and biodegradable composite made of polypyrrole nanoparticles and polylactide

    Biomaterials

    (2004)
  • C. Basavaraja et al.

    Synthesis and characterization of soluble polypyrrole-poly(epsilon-caprolactone) polymer blends with improved electrical conductivities

    Materials Chemistry and Physics

    (2011)
  • J.Y. Lee et al.

    Polypyrrole-coated electrospun PLGA nanofibers for neural tissue applications

    Biomaterials

    (2009)
  • P. Moroder et al.

    Material properties and electrical stimulation regimens of polycaprolactone fumarate-polypyrrole scaffolds as potential conductive nerve conduits

    Acta Biomaterials

    (2011)
  • M.Y. Li et al.

    Electrospinning polyaniline-contained gelatin nanofibers for tissue engineering applications

    Biomaterials

    (2006)
  • H.S. Kim et al.

    Biocompatible composites of polyaniline nanofibers and collagen

    Synthetic Metals

    (2009)
  • E.M. Stewart et al.

    Inhibition of smooth muscle cell adhesion and proliferation on heparin-doped polypyrrole

    Acta Biomaterials

    (2012)
  • X. Liu et al.

    Conducting polymers with immobilised fibrillar collagen for enhanced neural interfacing

    Biomaterials

    (2011)
  • S.A. Agnihotri et al.

    Recent advances on chitosan-based micro- and nano-particles in drug delivery

    Journal of Controlled Release

    (2004)
  • M. Rinaudo

    Chitin and chitosan: properties and applications

    Progress in Polymer Science

    (2006)
  • E. Zakhem et al.

    Chitosan-based scaffolds for the support of smooth muscle constructs in intestinal tissue engineering

    Biomaterials

    (2012)
  • A. Kotwal et al.

    Electrical stimulation alters protein adsorption and nerve cell interactions with electrically conducting biomaterials

    Biomaterials

    (2001)
  • P. Krol

    Synthesis methods, chemical structures and phase structures of linear polyurethanes. Properties and applications of linear polyurethanes in polyurethane elastomers, copolymers and ionomers

    Progress in Materials Science

    (2007)
  • E. Campos et al.

    Design and characterization of bi-soft segmented polyurethane microparticles for biomedical application

    Colloids and Surfaces B

    (2011)
  • I.H.L. Pereira et al.

    Photopolymerizable and injectable polyurethanes for biomedical applications: synthesis and biocompatibility

    Acta Biomaterials

    (2010)
  • S. Agarwal et al.

    Use of electrospinning technique for biomedical applications

    Polymer

    (2008)
  • T.J. Sill et al.

    Electro spinning: applications in drug delivery and tissue engineering

    Biomaterials

    (2008)
  • M.P. Prabhakaran et al.

    Electrospun conducting polymer nanofibers and electrical stimulation of nerve stem cells

    Journal of Bioscience and Bioengineering

    (2011)
  • I.S. Chronakis et al.

    Conductive polypyrrole nanofibers via electrospinning: electrical and morphological properties

    Polymer

    (2006)
  • S. Aznar-Cervantes et al.

    Fabrication of conductive electrospun silk fibroin scaffolds by coating with polypyrrole for biomedical applications

    Bioelectrochemistry

    (2012)
  • N. Gospodinova et al.

    Conducting polymers prepared by oxidative polymerization: polyaniline

    Progress in Polymer Science

    (1998)
  • S. Bhadra et al.

    Progress in preparation, processing and applications of polyaniline

    Progress in Polymer Science

    (2009)
  • M.R. Bagherzadeh et al.

    Investigation on anticorrosion performance of nano and micro polyaniline in new water-based epoxy coating

    Progress in Organic Coatings

    (2011)
  • B.D. Ulery et al.

    Biomedical applications of biodegradable polymers

    Journal of Polymer Science Part B: Polymer Physics

    (2011)
  • R. Langer et al.

    Tissue engineering

    Science

    (1993)
  • R. Ravichandran et al.

    Advances in polymeric systems for tissue engineering and biomedical applications

    Macromolecular Bioscience

    (2012)
  • S.F. Yang et al.

    The design of scaffolds for use in tissue engineering. Part 1. Traditional factors

    Tissue Engineering

    (2001)
  • G.P. Chen et al.

    Scaffold design for tissue engineering

    Macromolecular Bioscience

    (2002)
  • S. Van Vlierberghe et al.

    Biopolymer-based hydrogels as scaffolds for tissue engineering applications: a review

    Biomacromolecules

    (2011)
  • Cited by (481)

    View all citing articles on Scopus
    View full text