Biomimetic conducting polymer-based tissue scaffolds

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Highlights

  • Electrical stimulation is used in a number of FDA approved devices.

  • There are no FDA approved CP-based tissue scaffolds.

  • CP-based tissue scaffolds with biomimetic properties perform better in vitro.

  • CP-based biomaterials exhibit relatively low levels of immunogenicity in vivo.

Conducting polymer-based materials are promising for application as tissue scaffolds for the replacement or restoration of damaged or malfunctioning tissues, because a variety of tissues respond to electrical stimulation. This review focuses on conducting polymer-based materials with biomimetic chemical, mechanical and topological properties, and recent progress toward the fabrication of clinically relevant tissue scaffolds is highlighted.

Introduction

Electromagnetic fields affect a variety of tissues (e.g. cardiac, muscle, nerve and skin) and play important roles in a multitude of biological processes (e.g. angiogenesis, cell division, cell signaling, nerve sprouting, prenatal development, and wound healing), mediated by a variety of subcellular level changes, including protein distribution, gene expression, metal ion content, and action potential [1••]. This basic science has inspired further research into the development of electrically conducting devices for biomedical applications including bioactuators, biosensors, drug delivery devices, cardiac/neural electrodes, and tissue scaffolds [2•, 3•, 4•, 5•]. It is particularly noteworthy that there are already a number of FDA approved devices capable of electrical stimulation of the body, including: pacemakers (bladder, cardiac, diaphragmatic and gastric), electrodes for deep-brain stimulation (for the treatment of dystonia, essential tremor and Parkinson's disease), spinal cord stimulators for pain management, vagal nerve stimulators for seizure/hiccup management, devices to improve surgical outcomes for cervical fusion surgery for patients at a high risk of non-fusion, and non-invasive devices to stimulate bone growth.

Polymer-based materials are ubiquitous in everyday life, and conducting polymers (CPs) are currently being investigated for a wide variety of biomedical applications [2•, 3•, 4•, 5•] and the most commonly employed CPs are shown in Figure 1. CPs are attractive for the preparation of biomaterials due to their simple synthesis and modification, which facilitates the tuning of their bulk and surface chemistry that governs their physicochemical properties [3•, 4•]. However, the preparation of clinically relevant CP-based tissue scaffolds with biomimetic chemical, mechanical and topological properties (as illustrated in Figure 2) is still challenging, and we will discuss recent progress in this direction in the following sections.

Section snippets

Synthesis of conducting polymers

CPs are most commonly synthesized either via electrochemical polymerization of the constituent monomers at the surface of an electrode [6] or in the solution/solid state in the presence of a catalyst (e.g. an oxidant such as FeCl3) [7]. To conduct electricity, conjugated polymers need to be oxidized or reduced; the processes of oxidation or reduction result in the backbone of the polymer being ionized, which necessitates the presence of counter ions that are commonly known as dopant ions (in

CP-based tissue scaffolds with biomimetic chemical properties

The natural extracellular matrix (ECM) is a mixture of proteins and polysaccharides that display biochemical cues that influence cell behavior, and determine how efficiently cells adhere to them via interactions with glycoproteins displayed on the cell surface. Integrins are an important class of cell adhesive glycoproteins that recognize specific peptide sequences in ECM proteins such as collagen, fibronectin, laminin and vitronectin, and biomimetic biomaterials intended for use as tissue

CP-based tissue scaffolds with biomimetic mechanical properties

Biological tissues have characteristic mechanical properties, and cellular behavior is known to be influenced by mechanical stimuli through a variety of mechanisms broadly classed as mechanotransduction [35]. Mismatch between the mechanical properties of a tissue scaffold and the tissue in which it is implanted may lead to inflammation of the surrounding tissue, followed by the encapsulation of the implanted scaffold within an avascular network of fibrous tissue [36]. Hence, the fabrication of

CP-based tissue scaffolds with biomimetic topological properties

Natural tissues are 3-dimensional (3D) composite materials with characteristic topological properties that are essential for their function [43]. Anisotropic features are commonly observed in functional tissues (including cardiac, ligament, musculoskeletal, nervous and vascular tissues), often in the form of anisotropically distributed components of the extracellular matrix, which influences the alignment, morphology and behavior of the resident cells. The development of tissue scaffolds that

CP-based tissue scaffolds in vivo

CP-based materials are attractive candidates as scaffolds for bone, muscle and nerve tissues which are responsive to electrical stimuli (Table 1). A factor of key importance for the clinical translation of CP-based tissue scaffolds is their immunogenicity, which is ideally very low. Histological analyses of tissue in the vicinity of polypyrrole-based tissue scaffolds implanted subcutaneously or intramuscularly in rats, reveal immune cell infiltration compared to FDA-approved poly(lactic

Conclusions

In this review we have chosen to focus on CP-based tissue scaffolds with biomimetic chemical, mechanical and topographical properties, highlighting recent progress toward the fabrication of clinically relevant tissue scaffolds. The results of both in vitro and in vivo studies suggest that CP-based tissue scaffolds are promising candidates for the electrical stimulation of the recovery of bone, muscle and nerve tissues in the clinic.

We believe that there is great potential for the development of

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

References (70)

  • B. Guo et al.

    Electroactive porous tubular scaffolds with degradability and non-cytotoxicity for neural tissue regeneration

    Acta Biomater

    (2012)
  • L. Huang et al.

    Synthesis of biodegradable and electroactive multiblock polylactide and aniline pentamer copolymer for tissue engineering applications

    Biomacromolecules

    (2008)
  • R.A. Green et al.

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

    Biomaterials

    (2008)
  • G. Justin et al.

    Electroconductive blends of poly(HEMA-co-PEGMA-co-HMMA-co-SPMA) and poly(Py-co-PyBA): in vitro biocompatibility

    J Bioact Compat Polym

    (2010)
  • I. Jun et al.

    The stimulation of myoblast differentiation by electrically conductive sub-micron fibers

    Biomaterials

    (2009)
  • V. Strong et al.

    Direct sub-micrometer patterning of nanostructured conducting polymer films via a low-energy infrared laser

    Nano Lett

    (2011)
  • B. Weng et al.

    Inkjet printed polypyrrole/collagen scaffold: a combination of spatial control and electrical stimulation of PC12 cells

    Synth Met

    (2012)
  • Z. Wang et al.

    In vivo evaluation of a novel electrically conductive polypyrrole/poly(d,l-lactide) composite and polypyrrole-coated poly(d,l-lactide-co-glycolide) membranes

    J Biomed Mater Res A

    (2004)
  • S.S. Mihardja et al.

    The effect of polypyrrole on arteriogenesis in an acute rat infarct model

    Biomaterials

    (2008)
  • S.C. Luo et al.

    Poly(3,4-ethylenedioxythiophene) (PEDOT) nanobiointerfaces: thin, ultrasmooth, and functionalized PEDOT films with in vitro and in vivo biocompatibility

    Langmuir

    (2008)
  • Y. Liu et al.

    Nano-hydroxyapatite surfaces grafted with electroactive aniline tetramers for bone-tissue engineering

    Macromol Biosci

    (2013)
  • G.G. Wallace et al.

    Nanobionics: the impact of nanotechnology on implantable medical bionic devices

    Nanoscale

    (2012)
  • A.-D. Bendrea et al.

    Review paper: progress in the field of conducting polymers for tissue engineering applications

    J Biomater Appl

    (2011)
  • N.K. Guimard et al.

    Conducting polymers in biomedical engineering

    Prog Polym Sci

    (2007)
  • A. Guiseppi-Elie

    Electroconductive hydrogels: synthesis, characterization and biomedical applications

    Biomaterials

    (2010)
  • J. Heinze et al.

    Electrochemistry of conducting polymers  persistent models and new concepts

    Chem Rev

    (2010)
  • J.M. Fonner et al.

    Biocompatibility implications of polypyrrole synthesis techniques

    Biomed Mater

    (2008)
  • Z. Ma et al.

    Surface modification and property analysis of biomedical polymers used for tissue engineering

    Colloids Surf B Biointerfaces

    (2007)
  • K.G. Sreejalekshmi et al.

    Biomimeticity in tissue engineering scaffolds through synthetic peptide modifications  altering chemistry for enhanced biological response

    J Biomed Mater Res A

    (2011)
  • R.A. Green et al.

    Cell attachment functionality of bioactive conducting polymers for neural interfaces

    Biomaterials

    (2009)
  • J.Y. Lee et al.

    Pyrrole–hyaluronic acid conjugates for decreasing cell binding to metals and conducting polymers

    Acta Biomater

    (2010)
  • S.J. Wilks et al.

    In vivo polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT) in rodent cerebral cortex

    Conf Proc IEEE Eng Med Biol Soc

    (2011)
  • J.W. Lee et al.

    Carboxylic acid-functionalized conductive polypyrrole as a bioactive platform for cell adhesion

    Biomacromolecules

    (2006)
  • A.B. Sanghvi et al.

    Biomaterials functionalization using a novel peptide that selectively binds to a conducting polymer

    Nat Mater

    (2005)
  • J. Nickels et al.

    Surface modification of the conducting polymer, polypyrrole, via affinity peptide

    J Biomed Mater Res A

    (2013)
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