# Immobilization of Detonation Nanodiamonds on Macroscopic Surfaces
## 1 Introduction  
Titanium and titanium-based alloys have been used as implant material for a long time, due to their high ratio of tensile strength and Young's Modulus (\(\sigma\)U/E), excellent corrosion properties, and high biocompatibility, respectively [1]. The rate and quality of osseointegration in Ti implants are strongly related to their surface properties. Surface composition, hydrophilicity, and roughness are parameters that play a significant role in implant-tissue interaction and osseointegration [2; 3]. However, Ti and its alloys cannot meet all of the clinical requirements. Therefore, in order to improve the biological, chemical, and mechanical properties, surface modification is often performed [4], using anodic oxidation [5], calcium phosphate/hydroxyapatite [6], bioactive glasses [7], diamond-like carbon (DLC) [8], and microwave plasma chemical vapor deposition (MPCVD) of nanodiamond films [9]. MPCVD nanodiamond films possess biocompatibility and chemicalinertness [10], but these techniques require specialized and expensive equipment compared to wet-chemical detonation nanodiamond (ND) coatings [11]. In order to enhance the osseointegration of oral Ti implants, some implant systems have surface nanostructures and bioactive ion chemistry (calcium, fluoride, or strontium [12]), or nanometer-sized calcium phosphate coatings, which are currently in clinical use [13; 14; 15]. Nevertheless, it is difficult to draw conclusions about which surface factor (i.e., nanotopography or surface ion chemistry) plays the more dominant role in implant osseointegration [16]. It has been reported that the bone cells are accustomed to a nanoscale environment rather than to a microscale environment [17]. For instance, osteoblasts were found to proliferate more quickly on nanostructured alumina and hydroxyapatite than on conventional counterparts [18]. At the same time, increasing attention is being given to prospects in medical and biological applications of NDs, due to their nontoxicity, as well as their structural, surface, and spectroscopic properties [19; 20]. ND research has extended into the biomedical field, with recent in vitro and in vivo animal studies that demonstrate that NDs are biocompatible and non-toxic, even to human cells [21]. Biofunctional NDs are used to prevent secondary tumour formation in mice [22], and NDs show full clearance in mice after 10 days [23]. Novel in vitro studies have demonstrated the absence of cytotoxicity in NDs [24], suggesting the use of NDs as biolabels [25] and drug delivery vehicles [26]. Moreover, protein-functionalized NDs are nontoxic and can enter mammalian cells efficiently [27]. In-vivo studies have included oral, subcutaneous, intramuscular, and intravenous administration of sterile ND hydrosols [28]. It is feasible to link NDs to actin filaments [29] or glycoproteins [30], so the variety of possibilities to conjugate NDs is great [31]. The study of ND effects on the growth and development of chicken embryos found that NDs may reduce blood vessel formation and affect the development of the circulatory system by inhibiting proangiogenic factor bFGF (basic fibroblast growth factor) [32]. [PERSON] et al. showed that macrophage cell proliferation and metabolic activity were significantly reduced in the presence of ND wear debris. In contrast, ND exposure significantly reduced the expression of several genes that play key roles in inflammation and related bone loss, including tumour necrosis factor and platelet derived growth factor [33]. Oxygen-terminated NDs immobilized on glass have shown a confluent cellular attachment of human neural stem cells, and enhanced cell adhesion compared to bare glass [34]. Monolayers of NDs universally promote murine hippocampal neuronal adhesion, wherein smaller-sized NDs promote greater neurite extension [35]. [PERSON] et al. showed the high biocompatibility of immobilized NDs using layer-by-layer deposition of poly-l-lysine and ND-drug conjugates [36]. The above investigations prove the feasibility of ND coatings for biomedical applications.