## 3 Fn Application and Involvement in Biomaterials and Medical Device Engineering
### Fn 2D Molecular Coatings
#### 3.1.2 Fn Physical Adsorption  
Physical adsorption can lead to unstable coatings; however, it is less damaging for the conformation of the adsorbed molecules. [PERSON] et al. investigated the bioactivity of adsorbed Fn vs. Fn covalently immobilized on polyethylene terephthalate (PET) [52]. They showed that adsorbed Fn results in higher accessibility for the RGD domain and bioactivity. Over the last few decades, Fn adsorption on various biomaterial surfaces has been analyzed and garnered great interest in different contexts. The overall surface properties of a biomaterial, such as the chemical composition, topography and roughness, hydrophobicity, and surface energy, influence the adsorption, structure, and function of proteins and have impacts on cell responses [53; 54; 55]. Several studies have shown the influence of surface topography on Fn adsorption. Microtopography leads to a heterogeneous adsorption of the protein: on rough or micro-grooved surfaces, Fn is preferentially adsorbed on peaks or onto groove/ridge boundaries [56; 57]. Nanostructures at the surface also influence the amount of Fn adsorbed, but in this case, a homogeneous deposition of 10-20 ug/mL Fn solution has been observed [58]. In all cases, great impacts on cell spreading, adhesion, and the size of focal adhesion have been observed. Interactions between Fn and polymeric surfaces have been demonstrated to be influenced by surface hydrophobicity. Early studies revealed that the amount of Fn adsorbed on hydrophobic surfaces is higher, but the protein is less active [59; 60]. The loss of Fn's bioactivity could be directly linked to Fn's conformation: on a hydrophilic substrate, atomic force microscopy (AFM) images highlighted an elongated conformation of Fn and, thus, the exposure of specific binding sequences were obtained, whereas on hydrophobic substrates, a more compact structure was observed [61]. [PERSON] et al. also demonstrated that, even though the surface densities of Fn adsorbed onto a hydrophilic silica surface and a hydrophobic polystyrene surface are identical, Fn retains a native conformation on the hydrophilic substrate while exhibiting an alteration of the globular module on the hydrophobic material [19]. To assess the impact of surface chemistry on Fn adsorption and conformation, self-assembled monolayers presenting different terminated groups were used as model surfaces. Fn adsorption on gold surfaces modified by self-assembled monolayers (SAMs) of alkanethiols terminated with CH\({}_{3}\), OH, COOH, and NH\({}_{2}\) functionalities led to differences in the accessibility of the integrin-binding domain [62] and, therefore, had a direct impact on cell adhesion and spreading, with higher cell responses on OH-SAMs [54]. Protein conformation and integrin-binding site accessibility play key roles in early cell adhesion; however, [PERSON] et al. showed that the force of protein adsorption on a biomaterial and protein reorganization carried out by cells affect long-term cell adhesion and are directly related to surface chemistry [63]. Recently, surfaces exhibiting a specific chemistry--poly(ethyl acrylate) (PEA)--have been shown to induce Fn fibrillogenesis, a process usually driven by cells, leading to the formation of a physiological fibrillar network [64; 65]. On these surfaces, Fn adsorbs in a conformation that permits the simultaneous exposure of the integrin-binding domain (Fn III-9 and -10) and GF-binding domain (Fn III-12-III-14), leading to a synergistic presentation of the GFs BMP2 and VEGF for bone regeneration or vascularization [66,67]. Biomaterial biofunctionalization with Fn is often used to enhance implant biointegration and biocompatibility, modulating the cell response. Fn adsorption on biomaterials has also been shown to modulate the inflammatory and wound-healing process that occurs after biomaterial implantation. Monocytes adhere to the material surface rapidly after implantation and become activated macrophages able to release proinflammatory cytokines [68]. [PERSON] et al.