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Posted: Aug 28, 2007
Nanotechnology is key to next-generation tissue and cell engineering
(Nanowerk Spotlight) In the medical field there is a huge demand for tissue regeneration technologies, which covers a wide range of potential applications in such areas as cartilage, vascular, bladder and neural regeneration. Just consider the need for bone and dental implants: Each year, almost 500,000 patients receive hip implants worldwide, about the same number need bone reconstruction due to injuries or congenital defects and 16 million Americans loose teeth and may require dental implants. The market for medical implant devices in the U.S. alone is estimated to be $23 billion per year and it is expected to grow by about 10% annually for the next few years. Unfortunately, medical implant devices have been associated with a variety of adverse reactions, including inflammation and fibrosis. It has been suggested that poor tissue integration is responsible for loosening of implants and mechanical damage to the surrounding host tissues. Based on an expanding body of biomedical nanotechnology research work, there is a growing consensus among scientists that nanostructured implant materials may have many potential advantages over existing, conventional ones. The key, as indicated in a number of findings, seems to be that physical properties of materials, especially with regard to their surface's nanostructure, affect cell attachment and eventually the tissue response to the implant. Although nanotopography mediated cell responses have been shown in previous work, the mechanism of these responses is mostly undetermined. New research has now been conducted to determine the influence of nanopore size on cellular responses. Interestingly, these studies have revealed that larger nanopores (200 nm) trigger DNA replication and cell proliferation via various signal transduction pathways.
"Because of the direct interactions with host cells and tissue, the surface properties of medical implants play a critical role in determining the host responses and reactivity" Dr. Liping Tang explains to Nanowerk. "Several lines of evidence reveal that surface topography can influence cellular responses and activities at tissue-implant interfaces both in vitro and in vivo. "Although the effects of surface topography on cellular responses have been widely reported, little is know about the molecular mechanism of nano-textured material-mediated cellular responses. The aim of our study was, therefore, to evaluate the cellular and molecular responses such as cell adhesion, morphology, and proliferation as well as the early gene expression of cells cultured on large (200 nm) and small (20 nm) nanopore textured surfaces."
SEM images showing cells interacting with nano-structured surfaces with 200 nm diameter of pores (left) and with 20 nm diameter of pores (right) at 470 magnification, bar = 50 µm. Differences in smooth muscle cells morphology cultured on nano-structured surfaces were observed. Cells exposed to larger pores (200 nm) are more flat, spread with more surface blebs and filopodia associated with the cells, whereas cells exposed to smaller pores (20 nm) are less flat, more round and have more microvilli for attachment. (Reprinted with permission from American Scientific Publishers)
Tang points out that their research has found that nanotopography affects not only cell morphology and proliferation but also gene profiles of vascular smooth muscle cells. "Despite of the relationship between cell responses including cell proliferation and gene expression, relatively little work has been done to investigate the effects of surface topography on the gene expression of exposed cells" he says.
"We found that several genes involved in cell adhesion, cell morphology, cell cycle, DNA replication, cell proliferation, and signaling transduction pathways are dependent on the surface nanotopography" says Tang. "Exposure to larger pores induced genes involved with cytoskeleton elements such as villin, myosin, cofilin, and caveolin that play an important role in cell morphology. In addition, cell proliferation is greater in cells exposed to 200 nm-pore membranes compared to 20 nm-pore membranes since exposure to larger pore surfaces induced expression
of genes involved in cell cycle, DNA replication, cell proliferation while reduced expression of genes involved in cell apoptosis."
The results from this University of Texas study seem to confirm the increasingly popular belief among nanomedical researchers that nanotopography coatings and surface structuring will improve the biocompatibility and safety of medical implant devices.
"The future of tissue and cell engineering depends on the development of next-generation biomaterials, the nanostructured materials" says Tang. "These materials must have control over cell attachment and development into tissue. Since surface topography influences many aspects of cellular and molecular responses, surfaces of implanted devices can be developed so that they can be engineered to the desired cell shape and cell responses, to the points of interests."
Tang believes that such a topographic modulation of cell response can be one of the most important considerations during the design and manufacture
of medical devices. "There is no doubt that nanodimensional surface has a great potential for use to design of the next generation of tissue-engineered replacements."