The Effect of Nanotopography on Modulating Protein Adsorption and the Fibrotic Response

Abstract

Understanding and modulating the cellular response to implanted biomaterials is crucial for the field of tissue engineering and regenerative medicine. Since cells typically reside in an extracellular matrix containing nanoscale architecture, identifying synthetic nanostructures that induce desirable cellular behaviors could greatly impact the field. Using nanoimprint lithography, nanostructured patterns were generated on thin film polymeric materials. The ability of these surfaces to influence protein adsorption, fibroblast proliferation and morphology, and fibrotic markers was investigated. Nanostructured features with aspect ratios greater than five allowed for less protein adsorption, resulting in decreased fibroblast proliferation and rounded cellular morphology. These nanofeatures also induced significantly lower gene expression of collagen 1a2, collagen 3a1, and growth factors such as connective tissue growth factor, integrin linked kinase, transforming growth factor b1 (TGF-b1), and epidermal growth factor, key factors associated with a fibrotic response. The results demonstrate that select nanostructured surfaces could be used to modulate the fibrotic behavior in cells and have the potential to be used as antifibrotic architecture for medical implants or tissue engineering scaffolds.

Tunable Microfibers Suppress Fibrotic Encapsulation via Inhibition of TGFβ Signaling

“…15 Future work should assess the effect of microfibers on other aspects of the inflammatory response, including recruitment of macrophages and other inflammatory cells. Moreover, although previous work indicates that a similar effect can be seen on polystyrene microtopography 19 , polymers other than polypropylene should be investigated to determine the optimal material for the reduction of the fibrotic response using microfibers.…”

“…Color images available online at www.liebertpub.com/tea turn effect integrin engagement, filopodia formation, and myofibroblast differentiation), dramatic repression of differentiation is only observed on long microfibers, compared to relatively mild effects on short microfibers. 13,17,19,[34][35][36] Long microfibers are most likely interpreted by the cell as an increase in compliance, as increased microfiber length presents a more deformable interface. Therefore, the reduction in myofibroblast differentiation is likely in response to mechanosensing of a compliant material.…”

“…27 Of particular interest to implanted devices, Kam et al demonstrated that high-aspect ratio microfibers, produced by imprint lithography, reduced fibroblast proliferation and differentiation in vitro. 19 These high-aspect ratio microfibers may represent a method to leverage the well-documented effect of compliant materials on fibroblast behavior into a material that can be applied therapeutically or as an improvement to current designs. However, this study compared a variety of geometries without a systematic isolation of specific topographical feature dimensions (e.g., fiber height or width), making it difficult to identify the minimum necessary physical parameters that lead to knockdown of the fibrotic response via topography.…”

An academic, clinical and industrial update on electrospun, additive manufactured and imprinted medical devices

“…The cellular mechanisms that regulate topography-mediated differential cell function may be direct [105] (the physical influence of topography) and/or indirect (the chemical influence of topography, as a result of changes to the composition, orientation or conformation of adsorbed extracellular matrix components) [106,107]. The mechanisms by which anisotropic topography and ordered protein deposition influence cellular proliferation and differentiation are still being elucidated; however, they are thought to be driven by integrinfocal adhesion activation leading to changes to the cytoskeletal morphology and contractility [108].…”

The Influence of Anisotropic Nano- To Micro-Topography on in Vitro and in Vivo Osteogenesis

“…Bottom-up approaches, such as self-assembly, favor the use of biodegradable natural or synthetic polymers and peptides due to mild processing conditions [66][67][68][69][70][71][72][73][74][75], while top-down approaches, such as lithography, primarily utilize nonabsorbable synthetic polymers [76][77][78][79][80][81][82][83][84][85][86], due to the more robust nature of the polymers. However, advances in engineering have now made available capillary force lithography [87,88] and cast-mould techniques [89,90] that allow incorporation of nanofeatures on biodegradable polymers.…”