Electrically Conductive Materials: Opportunities and Challenges in Tissue Engineering

Abstract

Tissue engineering endeavors to regenerate tissues and organs through appropriate cellular and molecular interactions at biological interfaces. To this aim, bio-mimicking scaffolds have been designed and practiced to regenerate and repair dysfunctional tissues by modifying cellular activity. Cellular activity and intracellular signaling are performances given to a tissue as a result of the function of elaborated electrically conductive materials. In some cases, conductive materials have exhibited antibacterial properties; moreover, such materials can be utilized for on-demand drug release. Various types of materials ranging from polymers to ceramics and metals have been utilized as parts of conductive tissue engineering scaffolds, having conductivity assortments from a range of semi-conductive to conductive. The cellular and molecular activity can also be affected by the microstructure; therefore, the fabrication methods should be evaluated along with an appropriate selection of conductive materials. This review aims to address the research progress toward the use of electrically conductive materials for the modulation of cellular response at the material-tissue interface for tissue engineering applications.

Keywords: biomaterials; cell response; electrically conductive materials; interface; nanomaterials; regenerative medicine; tissue engineering.

Figure 1

Conducive platform’s properties are adjustable with various tissues [14,43]. The plot in the left-hand side gives advice on selection of biomaterials for a target tissue considering their conductivity and mechanical properties, while the right-hand one provides the investigator with a brief view over microstructure–property–performance relationship when one takes first step in selection of conductive biomaterials for tissue engineering and regenerative medicine uses.

Figure 2

Effect of the electrical stimulation on the cell morphology and proliferation. Fluorescence microscopy of PC12 cells without stimulation, with constant 10 µA of stimulation and 10 µA, 20 Hz of stimulation. Electrical stimulation enhances cell proliferation. Amplitude stimulation affects the cell morphology [45], copyright Elsevier, 2011.

Figure 3

PC12 behavior on polypyrrole (PPy)/polycaprolactone (PCL) platform with various dopants. Cell proliferation on conductive polymer has been affected by dopant type which dramatically affect the cell proliferation, morphology and behavior. The different scaffolds are (A,B) PCL, (C,D) PCL/PPY-NSA, (E,F) PCL/PPY-DBSA, (G,H) PCL/PPY-DOSS, (I) PCL/PPY-PI, (J) PCL/PPY-lysine. Dodecylbenzene sulfonic acid (DBSA) and naphthalene sulfonic acid (NSA) as a dopant enhanced cell proliferation than others [50], copyright Elsevier, 2010.

Figure 4

Electro-responsive tetraaaniline-PEG rod-coils in aquatic media, (a) chemical structures of TetraAaniline-PEG in the various oxidation states. (b) Redox switching results in vesicles rupture. (c) Hydrogen bonding of TAPEG [83], copyright American Chemical Society, 2011.

Figure 5

Culturing Schwann cell on conductive substrate affected the cell morphology and orientation. Moreover, micropatterning along with conductivity affect the cell morphology and alignment. (a) flat substrate, (b) grooved substrate 50 μm, (c) grooved substrate 100 μm, (d) flat conductive substrate, (e) grooved conductive substrate 50 μm, (f) grooved conductive substrate 100 μm, (g) schematic of neurite length, (h) neurite orientation [145], copyright Elsevier, 2018.

Figure 6

Mechanism of Schwann cells’ (SCs’) myelination on conductive platform. Conductive films inhibit CaSR and PLCβ pathway, and then decline the intracellular Ca2 þ level [25], copyright Elsevier, 2016.

Figure 7

An interwoven structure of cardiac with aligned cell layers and biomimic scaffold with similar structure. Multiple layers of Yarn nanofiber can recapitulate the cardiac muscles which cause cell alignment and elongation [200], copyright American Chemical Society 2017.

Figure 8

Conductive adhesive hydrogel patches synthesis attached on myocardial infarction (MI) site. Pyrrole was capped dopamine, simultaneously polymerized using Fe³⁺ oxidation which acted as an adhesive and conductive substrate [202], copyright John Wiley and Sons, 2018.

Figure 9

(A) Direct current decreases the oxygen level and enhances the pH, which causes to increase of osteoblast proliferation (B) capacitive coupling results in increment of cystolic calcium through voltage gated calcium channels. (C) Inductive coupling stimulation results in a direct enhancement in intracellular calcium [235].

Figure 10

(a) Composite similar to the skeletal muscle structure, contain aligned myofibers formed through myoblast fusion together into multinucleated myotubes surrounded within the extracellular connective tissue. (b) Scheme of scaffolds fabrication [259], copyright American Chemical Society, 2015.