Chitosan-based nanofibers mats for tissue engineering

Polymer hydrogels resemble the natural living tissue due to their high water content and soft consistency. They find many applications in the design and production of contact and intraocular lenses, biosensors membranes, matrices for repairing and regenerating a wide diversity of tissues and organs. Polysaccharides such as chitosan and hyaluronic acid based hydrogels have shown a great potential for biomedical and pharmaceutical applications, on account of their remarkable compatibility with physiological medium. Besides, it is degraded in a physiological environment into non-toxic products, which make them outstanding candidates for short- to medium-term applications, especially for tissue engineering. In this respect, the preparation of nanometric fibers mats based on this polysaccharide are highly interesting as such structure mimics the one of skin extracellular matrix. Such nanofibrous materials can be prepared by electrospinning (Figure 1). This technique uses a high voltage to create an electrically charged jet of polymer solution to obtain polymer fibers ranging from nanometers to a few microns in diameter. We thus have investigated strategies allowing to generate chitosan based nanofiber mats exhibiting a mechanical resistance strong enough to be easily handled while keeping the peculiar features of chitosan hydrogels favoring the interaction with cells and soft tissues to provide efficient tissue reconstruction.

In a first strategy, polysaccharide-based nanofibers with a multilayered structure were prepared by combining electrospinning (ESP) and layer-by-layer (LBL) deposition techniques. Elastic nanofibers bearing charges at their surface were firstly prepared by electrospinning poly(ε-caprolactone) (PCL) with a polyelectrolyte precursor. After activation by adjusting the pH, the layer-by-layer deposition of chitosan and hyaluronic acid, can be used to coat the electrospun fibers. A multilayered structure is then achieved by alternating the deposition of the positively charged chitosan with the deposition of a negatively charged polyelectrolyte. These novel polysaccharide-coated PCL fiber mats remarkably combine the mechanical resistance typical of the core material (PCL) – particularly in the hydrated state –, with the surface properties of chitosan.

Besides, crosslinked nanofibrous mats of chitosan and polyethylene oxide blends, were successfully prepared via electrospinning technique followed by heat mediated chemical crosslinking. This chemical cross-linking allows adjusting the mechanical resistance of the mats while preserving their biocompatibility. In both cases, the control of the nanofiber structure offered by the electrospinning technology, makes the developed processes very promising to precisely design biomaterials for tissue engineering. Preliminary cell culture tests corroborate the potential use of such systems in wound healing applications.