Melanin and Melanin-Related Polymers as Materials with Biomedical and Biotechnological Applications-Cuttlefish Ink and Mussel Foot Proteins as Inspired Biomolecules

Abstract

The huge development of bioengineering during the last years has boosted the search for new bioinspired materials, with tunable chemical, mechanical, and optoelectronic properties for the design of semiconductors, batteries, biosensors, imaging and therapy probes, adhesive hydrogels, tissue restoration, photoprotectors, etc. These new materials should complement or replace metallic or organic polymers that cause cytotoxicity and some adverse health effects. One of the most interesting biomaterials is melanin and synthetic melanin-related molecules. Melanin has a controversial molecular structure, dependent on the conditions of polymerization, and therefore tunable. It is found in animal hair and skin, although one of the common sources is cuttlefish (Sepia officinalis) ink. On the other hand, mussels synthesize adhesive proteins to anchor these marine animals to wet surfaces. Both melanin and mussel foot proteins contain a high number of catecholic residues, and their properties are related to these groups. Dopamine (DA) can easily polymerize to get polydopamine melanin (PDAM), that somehow shares properties with melanin and mussel proteins. Furthermore, PDAM can easily be conjugated with other components. This review accounts for the main aspects of melanin, as well as DA-based melanin-like materials, related to their biomedical and biotechnological applications.

Keywords: adhesive material; biofilms; biomedical applications; coated nanoparticles; melanin; polydopamine; therapeutical devices.

Figure 1

Structural units of natural eumelanin and polydopamine melanin (PDAM). Monomers (a) dopamine (DA); and (b) Dopa, DHI; (c) DHICA; (d) the porphyrin-like tetramer; and (e) protomolecule proposed as a putative symmetrical unit of melanin polymer to account for some properties, such as the high voltage output of battery devices built with PDAM coating on graphene or metal oxides. This tetramer can be a constituent of both natural melanin and synthesized PDAM.

Figure 2

(a) Proposed PDAM linear chain fragment. Units are linked by 4→7′ bonds. Uncycled and unordered DA, DHI, and 5,6-indolequinone units are represented; (b) Peptidic fragment (positions 41 to 47) of mfp5, ⁴¹KYYYKYK⁴⁷. Side chains of catechol (after tyrosine hydroxylation) and lysine residues are drawn. Hydroxy and amine groups are represented undissociated. The number of possible oxidation of catechol residues to quinones is unknown in both molecules, but cycling to indole units is only possible in PDAM. As higher the number of oxidized o-quinone residues, as lower the adhesive properties of mfps.

Figure 3

DA oxidation and formation of bare PDAM nanoparticles or deposition of a PDAM film on a surface of diverse material. At the beginning of the oxidation, DA is forming a stable colloidal suspension that is aggregating to particles of growing size, eventually into spherical PDAM nanoparticles. DA monomers and very small aggregates show adhesive properties, and they are able to deposit on a surface for coating, but after a threshold size, large PDAM nanoparticles do not coat, just precipitate.

Figure 4

PDAM nanoparticle and biomedical applications. The PDAM nanoparticles can be directly used, coated, co-polymerized with ions, such a as Gd(III) or Fe(III) for MRI or conjugated with other materials on the surface (i.e., activated PEG). Alternatively, primary nanoparticles of other material can be coated with PDAM. These nanoparticles can be used for antioxidant therapy or for photothermal therapy after laser irradiation. Finally, they can be charged by non-covalent interactions with active antitumoral agents for drug delivery. The alternatives may be combined in different stages according to the final application.