Design and applications of man-made biomimetic fibrillar hydrogels

Despite its long history and some preliminary work in tissue engineering nearly 30 years ago, electrospinning has not gained widespread interest as a potential polymer processing technique for applications in tissue engineering and drug delivery until the last 5-10 years. This renewed interest can be attributed to electrospinning's relative ease of use, adaptability, and the ability to fabricate fibers with diameters on the nanometer size scale. Furthermore, the electrospinning process affords the opportunity to engineer scaffolds with micro to nanoscale topography and high porosity similar to the natural extracellular matrix (ECM). The inherently high surface to volume ratio of electrospun scaffolds can enhance cell attachment, drug loading, and mass transfer properties. Various materials can be electrospun including: biodegradable, non-degradable, and natural materials. Electrospun fibers can be oriented or arranged randomly, giving control over both the bulk mechanical properties and the biological response to the scaffold. Drugs ranging from antibiotics and anticancer agents to proteins, DNA, and RNA can be incorporated into electrospun scaffolds. Suspensions containing living cells have even been electrospun successfully. The applications of electrospinning in tissue engineering and drug delivery are nearly limitless. This review summarizes the most recent and state of the art work in electrospinning and its uses in tissue engineering and drug delivery.

Never-dried and once-dried hardwood celluloses were oxidized by a 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated system, and highly crystalline and individualized cellulose nanofibers, dispersed in water, were prepared by mechanical treatment of the oxidized cellulose/water slurries. When carboxylate contents formed from the primary hydroxyl groups of the celluloses reached approximately 1.5 mmol/g, the oxidized cellulose/water slurries were mostly converted to transparent and highly viscous dispersions by mechanical treatment. Transmission electron microscopic observation showed that the dispersions consisted of individualized cellulose nanofibers 3-4 nm in width and a few microns in length. No intrinsic differences between never-dried and once-dried celluloses were found for preparing the dispersion, as long as carboxylate contents in the TEMPO-oxidized celluloses reached approximately 1.5 mmol/g. Changes in viscosity of the dispersions during the mechanical treatment corresponded with those in the dispersed states of the cellulose nanofibers in water.

The emergence of tissue engineering raises new possibilities for the study of complex physiological and pathophysiological processes in vitro. Many tools are now available to create 3D tissue models in vitro, but the blueprints for what to make have been slower to arrive. We discuss here some of the 'design principles' for recreating the interwoven set of biochemical and mechanical cues in the cellular microenvironment, and the methods for implementing them. We emphasize applications that involve epithelial tissues for which 3D models could explain mechanisms of disease or aid in drug development.