SUMMARY

   The aim of this Thesis is to investigate the use of hyaluronic acid as a material for the design of scaffolds aimed at CNS regeneration. The motivation comes from the need of searching for new strategies that allow regeneration in the central nervous system. In degenerative diseases, such as Parkinson’s disease, where the progressive loss of neuronal subpopulations occurs, a permissive environment able to support regeneration and connectivity of neurons from the host tissue may be a promising therapy to recover lost functionalities. In this Thesis we have focused on the development of structures able to integrate within the brain, supporting neural cells attachment and survival. 
   We hypothesized that hyaluronic acid provides an enabling environment and appropriate for regeneration due to its biocompatibility and diverses physiological applications. Biocompatible hydrogels based on modified hyaluronic acid were synthesized. Covalently crosslinked hyaluronic acid hydrogels, alone or in combination with acrylic polymers, were synthesized and permitted to develop different porous structures which may serve in different applications as cell supply, cell repopulation or tissue regeneration. Highly porous with interconnected spherical pores, hollow tubes or multichanneled scaffolds were developed. The processes allow for a wide range of shapes for different applications within the scope of central nervous system regeneration. 
   Furthermore, in vitro culture of human cell lines together with biomaterials was performed. A human microvascular endothelial cell line (hCMEC/D3) and a human glioma cell line (U373) were chosen for the studies. Experiments were focused on the interaction between hyaluronan based scaffolds and those cell lines composing the blood-brain-barrier (BBB) in the central nervous system. Biocompatibility, viability and phenotype characteristics were assessed. Hyaluronan based scaffolds did not elicit any inflammatory response when cultured with endothelial cells and demonstrated to be a good cue to the growth of both cell lines in mono and co-culture. In addition, endothelial cells (ECs) exhibited reorganization into cord-like structures within the biomaterials. The reorganization of EC is necessary as response of angiogenic stimuli and the formation of new vascular sprouts which will guarantee a favourable integration of the scaffold with the host tissue.  The influence of two different protein coatings prior to cell seeding was evaluated. On the one hand, laminin (LN), a protein derived from the basal lamina that participates in neuronal development, survival and regeneration; on the other hand, a coating of fibrin matrix (fb), which provides a suitable scaffolding for invading inflammatory, endothelial, and other tissue cells during the healing process. Results did not show noticeable differences between one protein and another in long periods of culture.