Hierarchical nanoengineered surfaces for enhanced cytoadhesion and drug delivery

Abstract

Delivering therapeutics to mucosal tissues such as the nasal and gastrointestinal tracts, is highly desirable due to ease of access and dense vasculature. However, the mucus layer effectively captures and removes most therapeutic macromolecules and devices. In previous work, we have shown that nanoengineered microparticles (NEMPs) adhere through the mucus layer, exhibiting up to 1000 times the pull-off force of an unmodified microsphere, and showing greater adhesion than some chemical targeting means. In this paper, we demonstrate that nanotopography improves device adhesion in vivo, increasing retention time up to ten-fold over unmodified devices. Moreover, we observe considerable adhesion in several cell lines using an in vitro shear flow model, indicating that this approach is promising for numerous tissues. We then demonstrate that nanowire-mediated adhesion is highly robust to variation in nanowire surface charge and cellular structure and function, and we characterize particle loading and elution. We present a form of cytoadhesion that utilizes the physical interaction of nanoengineered surfaces with subcellular structures to produce a robust and versatile cytoadhesive for drug delivery. These nanoscale adhesive mechanisms are also relevant to fields such as tissue engineering and wound healing because they likely affect stem cell differentiation, cell remodeling, migration, etc.

Micro/nanofabricated platforms for oral drug delivery

“…In an example of hierarchical microdevice structure, multi-layer fabrication was employed to modify one surface of 150 × 150 μm microdevices with microposts 10 μm in diameter [69]. In an alternate approach, bottom-up nanofabrication approaches have been employed to create nanoengineered microparticles (NEMPs) consisting of silicon oxide nanowire-coated silicon microparticles for oral drug delivery (Figure 3 C) [57, 70–73]. Following contact with an epithelial layer, the nanowire coating of these microparticles interdigitated with the microvilli on the surface of the epithelial cells [73].…”

Topography Design Concept of a Tissue Engineering Scaffold for Controlling Cell Function and Fate Through Actin Cytoskeletal Modulation

“…The techniques for fabrication of such hierarchical scaffolds have now been developed. 4,[97][98][99][100] Their effectiveness in enhancing MSC adhesion and proliferation has been shown using a scaffold consisting of microscale strands with deposited micro/nano-sized fibers. 99 Microspheres with nanowires improve adhesion to a wide range of cell types and ensure excellent in vivo biocompatibility while retaining high loading capacity inherent in micron-sized particles.…”

“…99 Microspheres with nanowires improve adhesion to a wide range of cell types and ensure excellent in vivo biocompatibility while retaining high loading capacity inherent in micron-sized particles. 100 Elasticity: an essential parameter for tuning effectiveness of micro/nanotopography as a structural constraint As discussed in the ''Cell Type-Specific Sensitivity to Topographical Features'' section, the effectiveness of micro/ nanotopography as a structural constraint varies by cell type because of cell type-specific sensitivity to topographical features. To cope with this cellular property in designing tissue engineering scaffolds, a design variable to tune how much the cell is constrained by micro/nanotopography should be taken into account.…”

Planar Bioadhesive Microdevices: A New Technology for Oral Drug Delivery

“…Currently, only a select number of microparticulate drug delivery systems have incorporated nanostructures to enhance oral drug delivery [75–77]. As microdevice design advances, future studies may apply a wide range of nanofabrication techniques to microdevice design as nanotopography has been shown to enhance muco- and cytoadhesion and interact with epithelial cells to enhance drug permeability [77–78].…”