Nanotopographical modification: a regulator of cellular function through focal adhesions

Abstract

As materials technology and the field of biomedical engineering advances, the role of cellular mechanisms, in particular adhesive interactions with implantable devices, becomes more relevant in both research and clinical practice. A key tenet of medical device design has evolved from the exquisite ability of biological systems to respond to topographical features or chemical stimuli, a process that has led to the development of next-generation biomaterials for a wide variety of clinical disorders. In vitro studies have identified nanoscale features as potent modulators of cellular behavior through the onset of focal adhesion formation. The focus of this review is on the recent developments concerning the role of nanoscale structures on integrin-mediated adhesion and cellular function with an emphasis on the generation of medical constructs with regenerative applications. KeywordsFocal adhesions; Biomaterials; Nanotopography; Cell signaling This review highlights the importance and development of the physiomechanical processes that regulate early cell-biomaterial interactions and the influence of nanoscale topographical modification on integrin-mediated cellular adhesion. As materials technology and the field of tissue engineering advance, the role of cellular adhesive mechanisms, in particular the interactions with implantable materials, becomes more relevant in both research and clinical practice.Biomaterials are never truly inert, being at best biotolerable. The cell-substratum interface functions as more than a simple boundary of definition between the host and an implanted device; instead, it presents primary cues for cellular adhesion and the subsequent induction of tissue integration. Indeed, the cytocompatibility of a material can be assessed in vitro by observing the viability and biofunctionality of cells at the substratum interface, paving the way for in vivo studies into device functionality. The range of materials currently designated as biomedically useful and their lack of biofunctionality reflects an increasing need for biomimetic constructs but also indicates the challenges present within the field. In particular a need exists to create truly biocompatible devices and ultimately to control the interactions that occur at the cell-substratum interface.A key tenet of medical device design has evolved from the exquisite ability of biological systems to respond to topographical features or chemical stimuli, a process that has led to the NIH Public Access Author ManuscriptNanomedicine. Author manuscript; available in PMC 2010 October 28. Published in final edited form as:Nanomedicine. 2010 October ; 6(5): 619-633. doi:10.1016/j.nano.2010.01.009. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript development of next-generation biomaterials. Recently published in the journal Science are the prerequisites for third generation biomaterials; not only should they support the healing site (as first-generation biomaterials), but they should be bioactive and possibly biodegradable...

Changes in embryonic stem cell colony morphology and early differentiation markers driven by colloidal crystal topographical cues

“…Since cell spreading, stimulated by ECM components promotes ESC differentiation by the activation of integrin signalling pathways (Hayashi et al, 2007) and conversely, the reduction of cell-substrate contacts promotes selfrenewal (Chowdhury et al, 2010), we suggest that culture on the SCC substrates, which inhibit spreading, in turn repress the effectors of integrin signalling, and therefore limits differentiation. A thorough review of the effects of feature spacing on integrin adhesion by Biggs et al also suggests that features in the size range we studied may disrupt integrin binding, which is consistent with the diminished colony spreading we observed (Biggs et al, 2010). Andersson et al found that human bladder cells on hemispherical structures appeared less spread than those on fl at samples with a corresponding decrease in cytokine production (Andersson et al, 2003).…”

Effects of a hybrid micro/nanorod topography-modified titanium implant on adhesion and osteogenic differentiation in rat bone marrow mesenchymal stem cells

“…41,42 Many studies have shown that nanotopographies dictate the differentiation activity of stem cells by influencing the phosphorylation of these two kinases. 43,44 Recent work has also demonstrated that the integrin-linked kinase/β-catenin pathway is important in mediating signals from topographical cues to direct osteogenic differentiation of cells. 45 The exact role of hybrid micro/nanorod topography in the response of the cell remains to be determined.…”

Integrating Mechanical and Biological Control of Cell Proliferation Through Bioinspired Multieffector Materials

“…Synthetic topographies affect basic functions in almost all types of mammalian cells. Therefore, engineering substrates within the size range at which ECM mechanical effectors trigger cell responses (4) offers a powerful tool to study and regulate complex cell functions such as adhesion, migration, cytoskeleton reorganization and cell polarization (5,1) that might be useful and exploitable for specific tissue engineering purposes.…”