Marine origin biomaterials for tissue engineering
Given the limited repair of human tissues, tissue engineering (TE) appears as the only solution to treat certain pathologies. TE consists on the development of suitable scaffolds able to support the cell growth, assisted by regeneration signals and creating the necessary microenvironment to favor the regeneration process. The Activity aims at approaching the value of marine materials (with a minor zoonosis risk) for medical applications through the development of innovative biomaterials and the assessment of their performance in tissue regeneration. It includes actions to purify different marine origin materials (focused on medicine) and their further use as suitable scaffolds, drug delivery systems and blending in advanced therapies as a proof of concept.
Some of the actions to develop aim at cartilage regeneration by the use of hydrogels based on marine origin low-immunogenicity collagen because it is exactly the destruction of its collagen what causes degeneration. On one hand with a view to regeneration, there will be tests with alternative hydrogels made of jellyfish and fisheries byproducts. Likewise, in order to reinforce and improve the mechanical properties of scaffolds (TI) and control the size of holes in the porous matrix a crosslinking of optimized transglutaminase will be used, easing the adhesion and proliferation of cells in the IT strategy.
Another issue to consider is the promotion of chondrogenesis avoiding the quick degradation of the growing factors of the fibroblasts involved. To do so, they will be included in nanoparticles produced with collagen hydrogels, which favor the control in the releasing of the growing factors.
With reference to chondrogenesis, it has been proved that Chondroitin sulfate glycosaminoglycan (GAG), a key compound in cartilage, has positive biological effects and that is why marine origin CS will be produced from cartilaginous fishes and blended with marine collagen to obtain hydrogels able to encapsulate chondrocytes and stem cells directed to cartilage regeneration.
Collagen is also present in skin; therefore, its regeneration in different wounds is basic for healing. With this goal, the work will be based on combinations of marine origin biopolymers as platforms for wound healing. The intention is using marine origin biopolymers to develop gels and sponges: jellyfish collagen or fisheries byproducts will be blended (crosslinking) with elastin and hyaluronic acid besides adding defined growing factors as an advanced therapy for wound healing.
Line 2Medical devices
This Activity focuses on the development of medical devices based on marine origin materials addressed to therapies for bone, cartilage and skin pathologies as well as to wound dressing, considered also as medical devices. The aim is proving the high potential of the isolated materials from marine byproducts for this sector of high added value medical devices. That is why the intention is developing prototypes of marine functional biomaterials whose industrial production may be integrated later in the business’ innovation chains.
One of the actions in this activity intends to create 3D structures based on collagen from fisheries byproducts (shark skin) and calcium phosphates (shark teeth) to assess and prove the potential of new natural compounds to support the culture of osteoblasts, promoting the osteogenic differentiation of stem cells and the future regeneration of bone tissue. The structures might be helpful to increase the efficiency in the differentiation of stem cells concerning the osteogenic lineage and the subsequent generation of bone tissue (functionalization with DNA and Bone morphogenetic proteins-BMPs).
The defects of complex tissues, covering both cartilage and bone, require advanced therapies like the tri-layered structures. Another action included in this Activity aims at assessing the potential of marine origin materials for this purpose, developing alternative structures. For instance: the use of the previously mentioned compounds as a mimicking bone layer, the type I collagen: hyaluronic acid as an intermediate layer and type II collagen: chondroitin sulfate as the mimicking cartilage layer, assessing their performance in animal models.
Bandages for skin care like wound protection are also part of this Activity. The goal of this action is developing medical devices that can be exploited for a further use as skin protector and wound dressing. Mixing high purity jellyfish collagen with Gellan gum, porous membranes/films with more cohesion and mechanical properties will be produced for wound protection and moisturize.
Another issue in this activity is the development of marine ceramics addressed for bone tissues therapies. Two main strategies will be carried out: on one hand, bioceramics with metallic particles will be produced to treat hyperthermia in bone illness and on the other hand, bioceramic nanoparticles from fish bones will be obtained to mix with collagen and produce nanocompounds to repair bone defects.
Line 3Marine Ingredients for cosmetics, well-being and healthcare products
This WP aims at identifying new marine compounds (from macroalgae, halophytes and cyanobacteria) with interesting bioactivity for the cosmetics and human health sectors. Specifically, the intention is studying new molecules with bone anabolic properties; new compounds with antimicrobial activity and/or anti-biofilm for cosmetics, medicine and health; extracts with anti-obesity activity for well-being and health, and nanoparticles-based systems to supply marine hydrolysates for cosmetics applications.
First, it will be produced from marine resources some purified extracts with bone anabolic properties and then the chemical structures will be characterized. Cyanobacteria and marine plants (macroalgae and halophytes) will be the work basis and the extracts obtained will be tested concerning their osteogenic/proliferative/mineralogenic activity, using fishes in vitro and in vivo. The same extracts will be tested concerning their antioxidant, antibacterial and anti-biofilm activity, as possible substitutes of the currently used additives, which usually have harmful side effects. The work will also involve the cytotoxicity of the alternative extracts.
Likewise, the aforementioned extracts could have an anti-obesity activity, that is why another action in this Activity will focus on its analysis to assess such ability regarding obesity and co-morbidities linked to that (diabetes & amp; fatty liver disease). The anti-obesity activity will be analyzed in zebra fish larvae by lipid coloration test, the anti-diabetes activity will be analyzed in zebra fish larvae and human liver cells by glucose bio catheters and the fatty liver disease will be analyzed in human liver cells by the lipid coloration tests. The cytotoxicity of the extracts will be included.
Finally, the nanocosmetics field will be also studied. Nanoemulsions and nanosomes will be produced basing on marine origin compounds, as vehicles to distribute bioactive ingredients (in particular collagen, hyaluronic acid hydrolysates and antioxidants from algae) for cosmetics applications. At the same time, functionality, physical properties and microbiological stability of the nanoparticles will be tested using cell lines and in vivo.