Biomimetic conducting polymer-based tissue scaffolds
Graphical abstract
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
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These authors contributed equally.