Chapter 1
Bioinspired Polydopamine and Composites for Biomedical Applications

Ziyauddin Khan1, Ravi Shanker1, Dooseung Um1, Amit Jaiswal2 and Hyunhyub Ko1

1Ulsan National Institute of Science and Technology (UNIST), School of Energy & Chemical Engineering, UNIST-gil 50, Ulsan, 44919, Republic of Korea

2BioX centre, School of Basic Sciences, Indian Institute of Technology Mandi, Kamand, Mandi, 175005, Himachal Pradesh, India

1.1 Introduction

Understanding the systems and functions existing in nature and mimicking them led researchers to discover novel materials and systems useful in all disciplines of science, whether it is chemistry, biology, electronics, or materials science [1, 2]. Numerous biopolymers (carbohydrates and proteins) such as cellulose, starch, collagen, casein, and so on, are naturally occurring polymers and have vast application in the biomedical research field. In recent years, PDA, a bioinspired polymer having a molecular structure similar to that of 3,4-dihydroxy-l-phenylalanine (DOPA), which is a naturally occurring chemical in mussels responsible for their strong adhesion to various substrates, has been regarded as a promising polymer, with applications in energy, electronics, and biomedical fields, due to its chemical, optical, electrical, and magnetic properties [3, 4]. For example, PDA can be easily deposited or coated with any substrate type of one's choice, including superhydrophobic surfaces, making it a highly beneficial material for coating and strong adhesive applications [3]. PDA also has various functional groups such as amine, imine, and catechol in its structure, which opens up the possibility for it to be integrated covalently with different molecules and various transition metal ions, thus making it a prerequisite in many bio-related applications.

Herein, this chapter describes the general synthetic route, polymerization mechanism, key properties, and biomedical applications of PDA. PDA can be synthesized by oxidation and self-polymerization of dopamine under ambient conditions; however, it can also be synthesized by enzymatic oxidation and electropolymerization processes, which are discussed in detail. Furthermore, this chapter also gives a brief idea about the characteristic properties of PDA such as optical, electrical, adhesive, and so on, followed by an extensive discussion of its applications in drug delivery, bioimaging, tissue engineering, cell adhesion and proliferation, and so on, with a special focus on its conductivity.

1.2 Synthesis of Polydopamine

1.2.1 Polymerization of Polydopamine

In the general synthesis of PDA, the dopamine monomer undergoes oxidation and self-polymerization in an alkaline medium (pH > 7.5) with air as an oxygen source for oxidation. This self-polymerization of the oxidative product of dopamine reaction is extremely facile and does not require any complicated steps. Although the polymerization of dopamine looks simple, the synthesis mechanism has not yet been investigated comprehensively [3, 5]. As shown in Figure 1.1, it is believed that in an alkaline solution dopamine is first oxidized by oxygen to dopamine quinone, followed by intramolecular cyclization to leucodopaminechrome through Michael addition. The formed intermediate leucodopaminechrome undergoes further oxidation and rearrangement to form 5,6-dihydroxyindole, which may yield 5,6-indolequinone by further oxidation [6]. Both these indole derivatives can undergo branching reactions at a different position (2, 3, 4, and 7), which can yield various isomers of dimers and finally higher oligomers. These oligomers can self-assemble by dismutation reaction between catechol and o-quinone to form a cross-linked polymer [3, 6]. Furthermore, there have been various other reports in which the authors have tried to investigate the exact mechanism of PDA formation, but this aspect is still unclear [7-10].

Figure 1.1 Formation mechanism of PDA in an alkali solution.

(Reprinted with permission from Refs [5] and [3] Copyright 2011 and 2014 American Chemical Society.)

Along with the oxidation and self-polymerization of dopamine in an alkali solution, PDA can also be synthesized by enzymatic oxidation and electropolymerization processes [11-13]. Enzymatic polymerization has attracted considerable interest owing to its environment-friendly characteristics. Inspired by the formation of melanin in a living organism, dopamine has been enzymatically polymerized using laccase enzyme into PDA at pH 6 (Figure 1.2) [1]. In laccase-catalyzed polymerization, laccase gets entrapped into the PDA matrix, which offers great advantages in biosensing and biofuel cell applications. In contrast to the enzymatic process, dopamine can also be electropolymerized and deposited on the substrate at a given potential in a deoxygenated solution. However, the electropolymerization process requires highly conductive materials, which is one of the main disadvantages of this process of dopamine polymerization.

Figure 1.2 Graphical representation of the formation of PDA-laccase-MWCNT nanocomposite film on GCE for hydroquinone biosensing.

(Reprinted with permission from Ref. [1] Copyright 2010 American Chemical Society.)

1.2.2 Synthesis of Polydopamine Nanostructures

A great deal of attention has been paid of late toward the synthesis of monodisperse PDA nanoparticles and PDAs with different morphologies, which can be used for other applications such as chemical sensors, energy storage, and so on. The size of the PDA particles can be tuned using a different ratio of solvents and base [14, 15]. Usually, after the self-polymerization reaction, PDA tends to form uniform spherical particles after prolonged reaction up to 30 h. Ai et al. have demonstrated that the size of PDA spheres can be controlled by varying the ratio of ammonia to dopamine and thereby synthesize various sizes of PDA nanoparticles (Figure 1.3a-e) [14]. In another study, Jiang et al. reported that varying the amount of ethanol and ammonia can also tune the size of PDA particles (Figure 1.3f) [15].

Figure 1.3 (a-e) Schematic representation of sub-micron size PDA particles and their morphological study.

(Redrawn and reprinted with permission from Ref. [14] Copyright 2013 Wiley-VCH.) (f) Study of EtOH and ammonia concentration on PDA morphology.

(Redrawn and reprinted with permission from Ref. [15] Copyright 2014 Nature Publishing Group.)

Recently, PDA with some unique morphology, for example, PDA nanotubes, have also been reported using a template-based method. Yan et al. coated a PDA layer on ZnO nanorods as a template by self-polymerization reaction of dopamine; and later the ZnO nanorod template was etched by ammonium chloride solution, leaving behind hollow PDA nanotubes (Figure 1.4a) [16]. Xue et al. reported the scalable synthesis of PDA nanotubes using curcumin crystal as a template [17], as shown in Figure 1.4b. These PDA nanotubes are several tens of micrometers long with 40-nm wall thickness and 200- to 400-nm tube diameter, which can be tuned by stirring rate and curcumin crystal size. Further to nanotubes, freestanding films of PDA and hybrid PDA films have also been prepared for their use in structural color, by layer-by-layer assembly [18-20]. In one of the reports, Yang et al. have reported composite freestanding films of PDA with polyethyleneimine (PEI), which was grown on air/water interface [20]. The prepared film was a freestanding transparent film, more than 1 cm in diameter, 80 nm in thickness, and without any visual defects on the film surface as proved by field emission scanning electron microscopy (FESEM). The film size can be tuned by the container which holds the dopamine and PEI solution.

Figure 1.4 (a) Graphical representation of PDA nanotube synthesis and its high-resolution TEM images.

(Reprinted with permission from Ref. [16] Copyright 2016 Royal Society of Chemistry.) (b) PDA nanotube synthesis by curcumin crystals and its morphology.

(Reprinted with permission from Ref. [17] Copyright 2016 American Chemical Society.)

Although there has been excellent progress in preparing different shapes and sizes of PDA nanoparticles, producing monodisperse nanoparticles is still a challenge, which is an essential parameter in biological science to ensure consistency in experiments. In the near future we can expect that this field will make further progress in producing highly monodisperse nanoparticles.

1.3 Properties of Polydopamine

1.3.1 General Properties of Polydopamine

PDA is an analog of eumelanin (a type of natural melanin) due to the similarity in chemical structure/component, which leads to the resemblance in physical properties [3, 21, 22]. Therefore, PDA has been regarded as a natural biopolymer, which has been utilized as a coating material in various applications. PDA is most commonly known for its inherent adhesive property; but functionalities of PDA have not been limited to adhesion as it possesses various properties, which are listed and discussed here.

1. 1. Optical properties: PDA shows broadband absorption ranging from ultraviolet (UV) to visible region, which increases exponentially toward the UV spectrum as in the case of the naturally occurring analog eumelanin. The absorption in the UV region originates from oxidation of dopamine to dopachrome and dopaindole;...