Project Portugal 2030

Summary

Despite medical progress and ongoing efforts to identify effective therapeutic strategies, SCI remains a persistent and debilitating disorder globally, lacking an established therapeutic solution thus far. Approximately 50% of individuals with SCI experience permanent or complete paraplegia or tetraplegia, resulting in an irreversible loss of neurological function below the injury site. The limited regenerative capacity of the human spinal cord makes SCI nearly irreversible. Given the absence of a developed method to address this irreversibility, the exploration of spinal cord regeneration becomes crucial. The SeaJellySpine project aims to develop injectable hydrogels with enhanced wet tissue-adhesive properties and improved cell response. These hydrogels will be based on marine collagen and fucoidan modified with catechol groups, for enhanced adhesive properties. In order to use sustainable resources and to untap the potential of the ocean, it is intended to obtain collagen and fucoidan from marine resources, such as fish waste from food industry and distinct algae. As fucoidan presents anti-inflammatory and antibacterial properties, the developed bioadhesive hydrogels will be multifunctional and they will combine antibacterial and anti-inflammatory properties with the adhesive behavior given by the catechol groups. Combinations of these two materials with hyaluronic acid and chitosan modified with catechol groups will also be explored to produce hydrogels with tunable properties and different compositions, taking advantage of the different properties of the mentioned polymers. This step will be necessary to find the most adequate combinations of these materials for SCI repair. All the selected natural materials exhibit traits such as biocompatibility, biodegradability, and chemical stability, imperative for the intended application. It is also intended to explore the production of these hydrogels by distinct methods, such as thermal gelation, DOPA quinone-mediated covalent cross-linking and chemical cross-linking through the formation of hydrazone bonds, which would allow to analyze and, ultimately, achieve the more suitable methods to obtain hydrogels that could enhance SCI regeneration. The main innovation will lie in the development of new in situ-gelling systems that could be used by clinicians in an easy way as injectable materials to fill irregular spinal cord cavities, which combine the enhanced tissue- and cell-adhesion in the wet environment of the body with antibacterial and anti-inflammatory properties. These hydrogels will be evaluated by in vitro assays and the most promising hydrogels will be validated by in vivo studies. In vitro models are indeed important tools to evaluate injectable hydrogel efficacy in preliminary stages, however, one cannot underrate the fact that animal models are widely recognized as essential to the study by allowing the evaluation of pharmacokinetics and pharmacodynamics. These multifunctional hydrogels based on natural biomaterials promises a bright future for spinal cord injury treatment in the next decade or so; they might become a major arsenal for safer and more efficient treatments by supportive scaffolds that mimic the spinal cord's natural environment, promoting cell growth and tissue repair. The functionalization with the catechol groups ensures proper localization and the antibacterial and anti-inflammatory properties enhance this environment.