**1. Introduction**

Metals are widely used to replace damaged bones, especially load-bearing bones [1]. Any metal is a bioinert material, the use of which raises concerns about (poor) biocompatibility, inappropriate mechanical properties, and inflammatory/immune reactions caused by metal ion dissolution [2]. Surface modifications of dental or orthopedic metal-based implants enhance biocompatibility and functionality [3,4]. Surface treatments may be physical, chemical, or biological in nature. Physical methods may alter the surface morphology to induce attachment to regenerated bone, or oxidize the implant surfaces to increase hydrophilicity and reduce corrosion caused by micro-arc oxidation and anodizing [5]. Chemical methods alter the surface of implants without significantly affecting their bulk properties, yielding hard, wear-resistant hydrophilic surfaces. The various techniques include chemical vapor deposition (CVD), plasma vapor deposition (PVD), ionbeam deposition (IBAD), grafting techniques, and the use of self-assembling monolayers (SAMs) [6–9]. Biological methods effectively improve the biological properties of bioinert metal implants [10].

Synthetic biomimetic strategies enhancing the functionality of metal-based implants have focused principally on the addition of biomolecules to implant surfaces. Growth factors and protein-mimetic peptides improve the interactions between the implant and the biological environment, with preservation of the bulk implant's mechanical properties [11]. Reactive groups are required for biomolecular tethering. However, bioinert metal surfaces lack such groups. Surface active groups (e.g., –OH, –COOH, and –NH2) are essential for surface modification. Oxygen-terminal carbon-based materials facilitate strong physisorption of biomolecules to carbon-based materials [12].

Graphene oxide (GO) contains several reactive oxygen groups (e.g., C=O, COOH, OH, and C-O-C), suspends well in water, and interacts with biomolecules and drugs. The

**Citation:** Oh, J.-S.; Jang, J.-H.; Lee, E.-J. Electrophoretic Deposition of a Hybrid Graphene Oxide/Biomolecule Coating Facilitating Controllable Drug Loading and Release. *Metals* **2021**, *11*, 899. https://doi.org/10.3390/met 11060899

Academic Editor: Hyun-Do Jung

Received: 16 April 2021 Accepted: 28 May 2021 Published: 31 May 2021

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unique flake-type two-dimensional (2D) structure is associated with high drug loading per unit of GO mass; the GO surface area is high. GO exhibits good mechanical properties, good biocompatibility (especially in terms of osteoconductivity), and good antimicrobial activity. GO is an optimal coating for orthopedic implants [13,14]. There are many reports that carbon-based materials, such as graphene, combined with biomolecules (BM) are effective in regenerating bone tissue. Examples include complexes of carbon-based materials with BM such as BMP-2, FGFs, and Simvastatin [15–17]. In addition, these complexes have been produced in various forms, including film, coating, particles, scaffolds, and fibers, and the properties analyzed and widely applied in implants research for tissue regeneration [18–21]. Biomimetic surface modifications enhance implant function; however, biomolecules are vulnerable to high temperatures, strong acid/base conditions, and chemical solvents [22]. Therefore, many studies use natural biopolymers as a base material that can be processed in aqueous conditions to prevent the stability of biomolecules, or incorporate biomolecules after the fabricating process of base materials is completed [21,23]. In particular, the surface modifications of metal implants require the gentle condition for all processes including the preparation of BM-combined composites and deposition of them on the surface. The electrophoretic deposition (EPD) method can be used to form coatings from aqueous solutions at room temperature. EPD deposits colloidal particles in an aqueous electrolytic bath onto substrates. The coating time is short, and the coatings are uniform and continuous [24,25]. EPD has been used to produce graphene films, graphene-based reinforced composites, complex materials, interleaved porous structures, and nanoparticlespaced graphene films [26]. To modify the surfaces of implants used for hard-tissue engineering, researchers have sought to reduce internal corrosion, increase hardness, and enhance biocompatibility by the addition of biopolymers; however, few studies have explored combinations of GO with therapeutic drugs. We are the first to use EPD to develop GO-biomolecule (GO-BM) hybrid coatings of controllable thickness; the coatings contain large amounts of drugs. If BMs are exposed on an implant surface, an additional layer is required to protect the BMs from loss or denaturation during transplantation. Our method reduces BM damage and allows control of drug loading and release. It is a technology applicable to drug-eluting stents or orthopedic implants development, which is expected to lead to enhanced therapeutic effects. In this study, GO-EPD coatings for biomedical applications were evaluated in terms of composition, physical properties, cellular interactions, and drug release [27–30].

#### **2. Materials and Methods**
