# Ion Beam Nanopatterning of Biomaterial Surfaces
## 1 Introduction  
Over the last decades, the interactions between artificial materials and biological systems have been intensively studied because of their great importance in regenerative medicine, tissue engineering, and biosensing [1]. Relevant processes in this regard are biomolecular adsorption, cell adhesion, proliferation, and differentiation, all of which are influenced by the physicochemical properties of the surface [1, 2]. Among the many contributing factors, surface topography has been recognized early on as an important trigger for cell behavior [3, 4], and the following years have seen numerous studies that investigated the effects of various microscale surface topographic features on cellular response [5, 6, 7]. Due to continuous advances in micro and nanofabrication, the accessible feature sizes became smaller and smaller and eventually reached the sub-100 nm range [8]. Surprisingly, it was found that such sub-micron features can induce astonishingly pronounced and highly complex behaviors in adhering cells that are several tens of microns in size. Consequently, the response of biological systems to nanoscale surface topographic features has become the focus of intense research activities [9, 10].  
In order to study the effects of sub-micron surface topography on biomolecular adsorption and cell response, numerous top-down and bottom-up nanofabrication techniques have been utilized over the last two decades, including electron beam [11, 12] and nanoimprinting lithography [13, 14], anodic oxidation [15, 16], nanoparticle coating [17, 18], glancing angle deposition [19, 20], molecular beam epitaxy [21, 22], and colloidal lithography [23, 24], among others. Ion beam nanopatterning, i.e., the self-organized formation of regular nanoscale patterns during ion irradiation, however, has only rather recently been employed in this context, even though it is a well-established technique known for many decades [25, 26] that can produce well-defined nanopatterns with tunable dimensions on almost arbitrary surfaces over macroscopic areas [27]. Nevertheless, in the last few years,an increasing number of papers have been published that studied the interaction of such ion beam-nanopatterned surfaces with various biomolecules and cells. Remarkably, while many of those studies used ion beam nanopatterning for the fabrication of well-defined model surfaces to enable the detailed investigation of the involved molecular and biological processes, several works rather focused on the potential of the technique to optimize the biocompatibility of the surfaces of realistic implant materials such as titanium alloys.  
In this review, we shall start with a brief overview of nanoscale pattern formation during ion beam irradiation and highlight important aspects that should be considered when applying this technique to biomaterial surfaces. In Section 3, we first discuss recent studies that have investigated the adsorption of relevant biomolecules, namely proteins and peptides but also DNA, at such surfaces, before focusing on the response of mammalian tissue as well as bacterial cells. The final section provides some conclusions and addresses future directions and challenges.