The Effects of the Surface Topography of Micromachined Titanium Substrata on Cell Behavior in Vitro and in Vivo

Abstract

Surface properties, including topography and chemistry, are of prime importance in establishing the response of tissues to biomaterials. Microfabrication techniques have enabled the production of precisely controlled surface topographies that have been used as substrata for cells in culture and on devices implanted in vivo. This article reviews aspects of cell behavior involved in tissue response to implants with an emphasis on the effects of topography. Microfabricated grooved surfaces produce orientation and directed locomotion of epithelial cells in vitro and can inhibit epithelial downgrowth on implants. The effects depend on the groove dimensions and they are modified by epithelial cell-cell interactions. Fibroblasts similarly exhibit contact guidance on grooved surfaces, but fibroblast shape in vitro differs markedly from that found in vivo. Surface topography is important in establishing tissue organization adjacent to implants, with smooth surfaces generally being associated with fibrous tissue encapsulation. Grooved topographies appear to have promise in reducing encapsulation in the short term, but additional studies employing three-dimensional reconstruction and diverse topographies are needed to understand better the process of connective-tissue organization adjacent to implants. Microfabricated surfaces can increase the frequency of mineralized bone-like tissue nodules adjacent to subcutaneously implanted surfaces in rats. Orientation of these nodules with grooves occurs both in culture and on implants. Detailed comparisons of cell behavior on micromachined substrata in vitro and in vivo are difficult because of the number and complexity of factors, such as population density and micromotion, that can differ between these conditions.

Microtopography of metal surfaces influence fibroblast growth by modifying cell shape, cytoskeleton, and adhesion

“…22 For the smooth materials (SS, TE, and NE), the variation in micro-and nano-topography did not have an adverse influence on cell adhesion, and spreading, nor did it affect cell growth as shown earlier. 9 This corresponds with observations of fibroblast morphology observed on smooth surfaces 23 and previously reported osteoblast reactivity to smooth SS, Ti-6Al-4V, and Thermanox. 24 The standard roughened topography of titanium, to some extent, controlled cell adhesion and shape, though this ultimately presented no difficulty for cells.…”

Fibroblast and osteoblast adhesion and morphology on calcium phosphate surfaces

“…The behaviour of both fibroblasts and osteoblasts was studied. Fibroblasts are the predominant cells found in loose connective tissue and are important in wound repair mechanisms: fibrous encapsulation is caused by the fibroblast type cells adhering to their neighbours rather than the substrate (Brunette and Chehroudi, 1999). Fibroblasts play a role in producing many of the components essential to connective tissue, for example extracellular components such as glycosaminoglycans and, in fibrous tissue, collagen (Rae, 1981).…”

“…Fibrous encapsulation is known to occur to implants made of steel, usually with the presence of a liquid filled void between the tissue and implant (Woodward and Salthouse, 1986) and is thought to be due to the cells not adhering adequately to the surface (Richards, 1996), resulting in a destabilisation of the implant, an inhibition of tissue regeneration and repair as well as increasing the chances of infection (Albrektsson et al, 1981;Gristina, 1987;Brunette and Chehroudi, 1999). This invariably leads to the rejection and failure of the implant.…”

“…Osteoblasts are derived from undifferentiated mesenchymal stem cells (Davies, 1996). They have the ability to synthesize and produce extracellular matrix and to control its mineralisation (Brunette and Chehroudi, 1999) and thus regulate the ingrowth of bone to the implant. Osteoblasts are key cells with regard to implant performance and assessing their behaviour on a potential biomaterial may give insight into its likely biocompatibility.…”

Neurons sense nanoscale roughness with nanometer sensitivity

“…From this perspective, cellular response to external stimuli goes far beyond the bare ability of the cell to chemically sense specific ECM ligands and includes a wide range of physical cues that are generated at, or act on, the interface between cells and the surrounding environment. For instance, it has been observed that micrometer-scale roughness may affect cell proliferation and morphology (15,16), because it provides a quasi-biomimetic microenvironment to the cells. However, cell-substrate interactions are typically governed by complex mechanisms occurring at the nanoscale, which are generally referred to as nanobiointeractions (17).…”