Developing stimulus-responsive biomaterials with easy-to-tailor properties is a highly desired goal of the tissue engineering community. A novel type of electroactive biomaterial, the conductive polymer, promises to become one such material. Conductive polymers are already used in fuel cells, computer displays and microsurgical tools, and are now finding applications in the field of biomaterials. These versatile polymers can be synthesised alone, as hydrogels, combined into composites or electrospun into microfibres. They can be created to be biocompatible and biodegradable. Their physical properties can easily be optimized for a specific application through binding biologically important molecules into the polymer using one of the many available methods for their functionalization. Their conductive nature allows cells or tissue cultured upon them to be stimulated, the polymers' own physical properties to be influenced post-synthesis and the drugs bound in them released, through the application of an electrical signal. It is thus little wonder that these polymers are becoming very important materials for biosensors, neural implants, drug delivery devices and tissue engineering scaffolds. Focusing mainly on polypyrrole, polyaniline and poly(3,4-ethylenedioxythiophene), we review conductive polymers from the perspective of tissue engineering. The basic properties of conductive polymers, their chemical and electrochemical synthesis, the phenomena underlying their conductivity and the ways to tailor their properties (functionalization, composites, etc.) are discussed.
New advances in tissue engineering are being made through the application of different types of electrical stimuli to influence cell proliferation and differentiation. Developments made in the last decade have allowed us to improve the structure and functionality of tissue-engineered products through the use of growth factors, hormones, drugs, physical stimuli, bioreactor use, and two-dimensional (2-D) and three-dimensional (3-D) artificial extracellular matrices (with various material properties and topography). Another potential type of stimulus is electricity, which is important in the physiology and development of the majority of all human tissues. Despite its great potential, its role in tissue regeneration and its ability to influence cell migration, orientation, proliferation, and differentiation has rarely been considered in tissue engineering. This review highlights the importance of endogenous electrical stimulation, gathering the current knowledge on its natural occurrence and role in vivo , discussing the novel methods of delivering this stimulus and examining its cellular and tissue level effects, while evaluating how the technique could benefit the tissue engineering discipline in the future.
Cellular activity at the center of tissue-engineered constructs in static culture is typically decreased relative to the construct periphery because of transport limitations. We have designed a tissue culture system that perfuses culture medium through three-dimensional (3D) porous cellular constructs to improve nutrient delivery and waste removal within the constructs. This study examined the effects of medium perfusion rate on cell viability, proliferation, and gene expression within cell-seeded 3D bone scaffolds. Human trabecular bone scaffolds were seeded with MC3T3-E1 osteoblast-like cells and perfused for 1 week at flow rates of 0.01, 0.1, 0.2, and 1.0 mL/min. Confocal microscopy after 1 week of culture indicated that a flow rate of 1.0 mL/min resulted in substantial cell death throughout the constructs whereas lowering the flow rate led to an increasing proportion of viable cells, particularly at the center of the constructs. DNA analysis showed increases in cell proliferation at a flow rate of 0.01 mL/min relative to 0.2 mL/min and static controls. Conversely, mRNA expressions of Runx2, osteocalcin, and alkaline phosphatase were upregulated at 0.2 mL/min compared with lower flow rates as quantified by real-time RT-PCR. These data suggest that medium perfusion may benefit the development of 3-D tissues in vitro by enhancing transport of nutrients and waste within the constructs and providing flow-mediated mechanical stimuli.