Research lines/Videos

Production of biomaterials for bone tissue regeneration made of isolated compounds of marine by-products (collagen and calcium phosphates) combined with a synthetic polymer

Involved partners

UMINHO (coordinator), UVIGO, IIM-CSIC, DevelopBiosystem

Aim

Production of biomaterial composite blending polymeric and ceramic materials of marine origin with synthetic polymers for bone tissue engineering.

Description

Most of the marine by-products generated in the fish processing industry, such as skins, scales or fish bones, among others, are mainly used for the production of flours for animal feed, thus corresponding to a low value-added use.

However, the valorization of these by-products given their intrinsic composition can be improved and high-value compounds can be isolated. Collagens and calcium phosphates compounds are received great attention and interest from the cosmetic, pharmaceutical and biomedical industries.

This strategy will be developed in this action, with collaboration between research groups and company, with a proposal to the development of a biomaterial for medical application, namely in bone tissue engineering strategies. In this perspective, the use of collagen and marine calcium phosphates, similar to the constituents of human bone, will allow exploring a biomimetic strategy envisages mimicking the extracellular matrix. The incorporation of synthetic polymers will allow a better control of the mechanical properties in the biomaterial to be developed, assembly to the requirements of the bone tissue to be regenerated.

In order to achieve this final objective of the action, intermediate objectives were defined, regarding the biomaterial production of each main components (collagen, calcium phosphate and synthetic polymer), as well as the establishment of material processing technologies and evaluation biological performance.

Valorisation and modification of extracts of macroalgae for regenerative medicine

Involved partners

UVIGO, BETA INGENIERÍA, IIM-CSIC, CIQ-UP

Aim

Description

Advanced bioceramics of marine origin for metallic implant coatings. Production, testing and proof of concept

Involved partners

UVIGO, BETA Implants, IIM-CSIC, CIQ-UP

Aim

The goal of this collaboration is the improvement of the osseointegration of metallic implants through the use of advanced bioceramic coatings

Description

These coatings, other than the enhancement of the interaction between implant and alive tissue, may also provide additional properties of biological interest (antibacterial, antitumor, mineralizing, etc.) as a consequence of the addition of elements such as strontium, selenium, copper, zinc, or fluorine. Moreover, the use of using different implant supports will be studied and discussed in the frame of this project.

The pulsed laser deposition techniques (PLD), in opposition to other deposition techniques commercially available, allows a fine control of the processing parameters that, as a consequence, may lead to the production of coatings with better physical and chemical properties. The PLD (pulsed laser deposition) is based on the ablation process of target materials that lasers offer and then transfer it to the desired surface (In this case metallic implants or other supports that may be of medical interest).

This collaboration will be coordinated by the New Materials research group (FA3) of the University of Vigo, which has an extensive experience, together with the adequate equipment, for both the fabrication of bioceramic coatings (HA, BG, substituted HA, etc.) through the use of the PLD technique and the the production of porous bioceramics obtained from different precursors (vegetable, marine, etc.).

In addition to the fabrication of biomaterials, this group has a suitable expertise for the physical-chemical characterization of these materials through different techniques such as x-ray diffraction (XRD), x-ray photoelectronic spectroscopy (XPS), x-ray fluorescence (XRF), x-ray energy dispersion spectroscopy (EDS), Fourier transformed infrared spectroscopy (FTIR), Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), interferometric profilometry, Hg porosimetry and contact angle measurements. With respect to the biological characterization, the FA3 group owns a cell culture laboratory for materials biotesting and vast experience in the biocompatibility analysis of different biomaterials produced in their laboratories, with respect to adhesion, osteoblasts proliferation and/or differentiation, or osteogenic activity through the use several lines of cells, as for example pre-osteoblasts or osteoblasts MC3T3-E1 MG63.

In order to explore new sources for the fabrication of advanced bioceramic coatings, ablation targets obtained through other marine waste byproducts will be used, as well as alternative and commercial deposition techniques. Concerning this item, the IIM-CSIC will provide their huge experience on both the characterization and chemical compound isolation, while the Industrial Application of Lasers research group of the University of Vigo (FA5) will contribute with their knowhow on the use of lasers with industrial applications and the reutilization of other marine waste byproducts.

One of the aims of this initiative is the demonstration that these advanced bioceramic coatings may present additional properties of biological interest (antibacterial, antitumor, mineralizing, etc.). Here, the extensive experience of BEL-FEUP in the kinetics of biofilms growth, together with the equipment available in their laboratories, will provide an excellent contribution to the realization of this objective.

Finally, with respect to the proof of concept, the company BETA Implants will be responsible of this task. BETA Implants is a Galician engineering company with a devoted technological orientation, committed to the design, development and commercialization of implants for high quality osteosynthesis for veterinarian orthopaedic medicine.

Production and characterization of compounds with cosmetics activity from marine origin by-products (collagen, glycogen and hyaluronic acid of microbial origin)

Involved partners

IIM-CSIC (coordinator), IUVENOR, CETALGA

Aim

Biomaterials production, bioactivities analysis and formulation of cosmetic products based on biopolymers and marine extracts mainly isolated from fishing by-products

Description

Most of the wastes from the fish processing industry in Galicia are destined to the manufacture of fishmeal, where these by-products have a low level of valorization. In the specific case of skins and scales, more especially in the case of skin, one of the best studied valorization alternatives is the production of gelatin (Karim and Bhat, 2009), which led to the creation of companies dedicated to its production, mainly located in the places where the raw material are generated.

On the other hand, the cosmetic industry requires collagen and collagen hydrolysates as an active ingredient for the manufacture of various cosmetic products, being for many years the marine source as the preferred option. This preference is motivated by the problems caused by the presence of encephalopathies associated with various proteins of bovine origin and by the perception of the consumers that the ingredients of marine origin are associated with diverse beneficial and natural properties.

Likewise, hyaluronic acid, a high molecular weight polysaccharide belonging to the glycosaminoglycan group, is one of the "key" molecules in cosmetic formulations, due to its high water retention capacity (large amounts of hydrogen bonds water-hydroxyl along the macromolecule).

The cosmetic activity of algae extracts has been indicated in several studies. The existence of a potential algae production in both areas (Galicia and Northern Portugal) has been studied in previous projects (Biotecmar, Marmed and Novomar), so it seems appropriate to take advantage of the potential of these organisms for their application in cosmetic products formulated with marine compounds.

Marine compounds with antitumor activity as new active substances with pharmacological interest

Involved partners

CIIMAR (coordinator), UMINHO

Aim

To get of new molecules with anticancer activity

Description

These coatings, other than the enhancement of the interaction between implant and alive tissue, may also provide additional properties of biological interest (antibacterial, antitumor, mineralizing, etc.) as a consequence of the addition of elements such as strontium, selenium, copper, zinc, or fluorine. Moreover, the use of using different implant supports will be studied and discussed in the frame of this project.

The success of pharmacological therapeutics in the future depends on the existence of a constant flow of new molecules with the ability to bind to selected molecular targets. This is the case of anticancer chemotherapy and as new chemical entities are discovered, there is a need for new chemicals to modulate those targets.

The research in marine natural products (MNP) is rather recent but it produced already seven chemical entities approved for clinical use, being the success rate in drug discovery from MNP higher than the average in traditional pharmaceutical industry. Oceans are a very attractive resource for new molecules biodiscovery especially taken into account that we know only a small percentage of marine organisms and in special the marine microbiome.

In this action we will follow a strategy designed in order to valorize microbial resources of the Portuguese marine coastal areas, taken into account that we will isolate new chemicals with anticancer activity from these bioresources. We will use extracts of cyanobacteria that are a group of organisms’ producers of a wide variety of natural compounds. The final goal is to isolate and characterize the structure of molecules and their anticancer activity and eventually their chemical-physical optimization, taken into account their development as pharmaceuticals.  

Development of pharmaceutical application systems including omega3 fat acids

Involved partners

USC

Aim

Evaluation of cyclodextrins as excipients in solid or semi-solid formulations for topical and oral use including stable fatty acids omega-3 with adequate organoleptic characteristics.

Description

Recent research has highlighted the importance of essential fatty acids in health. DHA is essential in creating human neurons and retinas since it is the main fatty acid that forms its membranes. Several publications show that a deficit of fatty acids during the last 3 months of pregnancy and in the first 6 months of life can lead to problems in the formation of the retina and consequently in the vision, or in the creation of neurons and synapsis. In addition, it can affect the levels of intelligence developed by the individual.

Its effects have also been observed in other fields as cardiology, gastroenterology and urology. In the field of dermatology, it has been proven that fatty acids omega-3 can have a positive influence on wound healing or skin healing due to encouraging the fluidity of cell membranes and reducing the phase of related inflammation such as delayed wound healing, which is beneficial for the treatment of atopic dermatitis or psoriasis.

The formulation of essential fatty acids of animal and vegetable origin presents a particular problem associated with their instability, since they are rapidly degraded by oxidation and / or photolysis. In addition, those of animal origin, generally obtained from fishery residues, have a characteristic odor that produces rejection in direct ingestion or topical application.

Cyclodextrins are cyclic oligosaccharides with the ability to encapsulate a number of hydrophobic or unstable compounds, which promotes the enhancement and improvement of the solubility and stability of a large number of substances. The total or partial encapsulation of the molecules also allows to mask the poor organoleptic properties of certain molecules.

This action is focused on solving the problems associated with omega 3 fatty acids (stability and organoleptic properties), through the collaboration between the research group of USC and Biomega company aiming at the valorization of these products for therapeutic applications of topical or oral use.

Valorisation of marine peptones as a source of nitrogen for the industrial production of marine probiotic bacteria and lactic acid

Involved partners

USC (coordinator), IIM-CSIC, UCP, BIALACTIS

Aim

The aim of this action is to evaluate the possibility of using different marine peptones, obtained from by-products of species discarded by the fishing fleet, in the production of high biomass density of different marine and lactic acid bacteria with probiotic properties

Description

Probiotics are living microorganisms with beneficial effects on the host because of their ability to modulate intestinal health. Among microorganisms considered probiotic, lactic acid bacteria (LAB) are the most important for incorporation into human food. Lactobacillus and Bifidobacterium strains are used in the manufacture of many fermented foods, with in situ production of lactic acid and/or other organic acids (preservation) as well as some bioactive metabolites (vitamins, antioxidants, bioactive peptides, etc.). They are also marketed in the form of food supplements or nutraceuticals. In this sense, it is increasingly important to promote the industrial production of LAB cultures with high biomass density.

On the other hand, there are a number of bacteria with probiotic properties in marine cultures that have demonstrated their effectiveness in reducing the high larval mortality rates of fish aquaculture such as turbot or golden fish. They may be an alternative to the excessive use of antibiotics by this sector. However, there are two fundamental factors that prevent its actual implementation in aquaculture: 1) the current legislation; and 2) the high costs associated with the massive production of viable probiotic biomass.

/br>

LAB are nutritionally very demanding and the formulation of the culture medium requires specific care to ensure the delivery of essential growth substrates such as amino acids, peptides, vitamins, minerals, nucleic acids and other growth factors. In general, the culture medium for propagation constitutes a significant share of the costs of producing microbial biomass and may represent up to 70% of them. In fact, the nitrogen component tends to be the most expensive fraction of the medium. Peptones, one of the nitrogenous ingredients commonly used, represent not only a source of organic nitrogen but also a source of specific amino acids and peptides.

/br>

Several works have demonstrated the potential of by-products from agro-food industries as economic sources for the production of ingredients for the formulation of culture media for microorganisms. Recent studies developed by the consortium in the field of the NOVOMAR project demonstrated the positive role of different peptones obtained from Scyliorhinus canicula viscera as a source of organic nitrogen for the production of different LAB including probiotics for human and aquaculture applications.

/br>

In this context, the partners will evaluate the potential of using peptones obtained from different by-products of marine origin in the industrial production of probiotic strains for human application with the purpose of generating a productive cost-effect process generating higher yields using sustainable alternatives.

/br>

Application of marine gelatines as a replacement of fat in the reformulation of different foodstuff

Involved partners

: IIM-CSIC, UCP (leader)

Description

Gelatine is known as the collagen where the triple helix of tropocollagen becomes unstable and gets broken (total or partially) and therefore is water-soluble.

The quality of gelatines is directly proportional to the denaturalization degree and/or rupture of the original collagen.Their most common sources are the skins from terrestrial mammals (bovine and porcine) however seafood products have specific properties that may be very appreciated specially in cultures where the use of mammal’s origin gelatines is not allowed due to religious reasons.

Nevertheless, there are not many commercial references of marine gelatines in the market, thus increasing the interest to find new sources and develop ideal process to produce them. Fishing byproducts like tuna, shark and cod skins are the main source for the production of high quality gelatine because of the good extraction yield.

Among their different applications especially the development of foodstuff and nutraceuticals there are also pharmacology and nanotechnology products.
As for the foodstuff relative to nutraceutical formulations and functional food, gelatines may become an efficient substitute of fat increasing the protein content and decreasing the energetic value preserving the sensorial properties of the food product such as pates and dairy products. In recent years, the increasing concern about a more healthy diet has caused a higher search of low-fat products.

Development of antifouling strategies for industrial applications

Involved partners

LEPABE-FEUP, CIIMAR, UCP, IIM-CSIC, SMART

Aim

Development of surfaces and antifouling formulations for industrial application

Description

Biofouling is a major problem for several types of industries. Therefore, industry and the scientific community have been making efforts to develop new strategies that prevent or reduce biofouling. One of these strategies consists in the application of molecules which can act on microorganisms that form biofilms, and consequently promote biofouling.

Marine organisms have a wide metabolic diversity and, as such, are able to produce many compounds of industrial interest, namely with anti (bio) fouling properties. In particular, marine cyanobacteria, microalgae, crustaceans, cephalopods and fish have been exploited for the extraction of compounds, which can delay the development of biofilms or have antimicrobial properties that inactivate the biofilms. These compounds can be immobilized on surfaces, incorporated into surface coatings (for example in paints or varnishes), or further used in liquid formulations and foams.

Antimicrobial surfaces or surface coatings can be used in several scenarios, including the prevention of marine biofouling (ship hulls and other submerged structures) and also in the food industry. Likewise, liquid formulations have been used for the removal of already formed biofilms, but also for eventual surface conditioning prior to biofilm formation.

In the particular case of the food industry the main goal of interest is the development of surfaces that reduce biofilms development in order that industrial processes have to be interrupted less frequently for cleaning operations. Most of the biofilms that are found in the conventional industrial surfaces are constituted by several microorganisms belonging to different species - mixed biofilms. Therefore, when testing the developed surfaces, it is important not only to know the total reduction of the microbial load, but also to identify which microorganisms are more or less resistant.

This line of work aims to test extracts and products from marine organisms (cyanobacteria, microalgae - Porphyridium cruentum and Nannochloropsis oculata, Illex argentinus, Munida sp., Loligo opalescens) to assess their anti (bio) fouling potential.

These tests will be performed under conditions which mimic the actual environment where the surfaces will be place, in particular as regards the hydrodynamic conditions in actual use. Biofilm formation with cyanobacteria will also be carried out in order to test the efficacy of the extracts acquired. Sub-fractionation operations will enable the identification of the active compounds, which will be incorporated in paints, varnishes or other coatings, or used after formulation as biocidal agents in foams.

Tests will then be performed in real environments to evaluate the performance of the various solutions developed. The work will give rise to a set of products that will have application in several areas and that can be explored by the companies involved in the project.

Development of edible coatings structured at nano and microscale to increase shelf life and improve quality of foods

PARTNERS:

INL, UMinho

Objectives

The main objectives of this action are the production and characterization of active and functional edible coatings, with micro and nanostructured multilayers and based on polymers of marine origin for the extension of food shelf life.
For this, there are 4 specific objectives:

• Development of multilayer coatings using bio-based polymers (polysaccharides and proteins), and Layer-by-Layer and vibrational atomization techniques.
• Encapsulation and controlled release of bioactive compounds, aiming the development of innovative functional delivery systems for food aplications.
• Structural and functional characterization of the micro- and nanocoatings.

Description

Because of their non-biodegradability, synthetic-based coatings and packaging for food applications are being replaced by edible polymers of natural origin. Edible coatings and films, besides being a physical barrier that does not have to be removed before eating, can be used to increase the shelf life of foods. They can also be used for the addition of bioactive molecules (antimicrobials, antifungals and antioxidants) allowing a better protection and improving the quality and functionality of food.
The development of new nano-structures based on biological, edible and biodegradable materials, accompanied by a study of their properties and functionalities, as well as their use in compounds with low solubility in water are some of the major challenges for nanotechnology applied to food science that will be studied in this action. In particular, polymers of marine origin such as chitosan, gelatine or chondroitin sulphate will be used. These materials are particularly interesting for these applications because they are inexpensive, have capacity to form films at nanoscale, are non-toxic and are approved for use in foods.

Regarding production technologies, will be studied the scalability of multilayer deposition technique (using the Layer-by-Layer technique) using bio-based materials as well as the use of vibrational atomization to produce micro- and nanostructured coatings on food surfaces.
In addition, the mass transfer processes and the possible increase of bioactivity (because they are improved at the nanoscale) of the active compounds encapsulated and added to the coatings will be studied. On the other hand, the increased solubility and bioavailability of the bioactive substances having a limited use due to their lipophilic nature will also be evaluated.

Optosensors based on thin films of marine materials

PARTNERS:

CIQ-UP (coordinator), SARSPEC, IIM-CSIC

Aim

The scientific and technical objectives of this task are to prepare optical sensors from composites based on glycosaminoglycans extracted from various marine wastes.

Description

The sector of optical instrumentation and accessories for optical equipment is very competitive, and there is a need for constant innovation so that the company remains competitive and can meet the needs of the market.

As part of its commercial strategy, SARSPEC intends to develop optrodes initially for a limited set of chemical species and which, depending on market acceptance, may be extended to other chemical species. These products will allow competing with the sensors provided by other competing companies (eg Metrohm and OceanOptics).

As a market positioning strategy, the optical sensors to be developed will be different from those offered by these companies (oxygen and pH sensors) in order to extend the available sensors in the market and to not have a direct competition for the same products.

The group of Physical Chemistry, Analytical & Electrochemical (RG4) of the Research Center in Chemistry of the University of Porto (CIQ-UP) has a wide experience in analytical techniques, in the development of sensors and in the preparation and characterization of organic molecular imprinting materials, inorganic and composites that will allow the development of new materials for the preparation of films for optical sensors for metallic cations or emerging pollutants.

The Institute of Marine Research, State Agency of the High Council of Scientific Research (IIM-CSIC) in particular, the Food Biochemistry (BA) and Recycling and Valorisation of Residual Materials (REVAL) groups of the IIM-CSIC, have been working intensively in the development and optimization of different processes (biotechnological or chemical based) for the purification and recovery of waste water and by-products from the marine food industry, with the production of high added value compounds such as enzymes, collagen, gelatin, glycosaminoglycans (GAGs), glycogen among others.

These three partners will collaborate in the preparation of sensor elements for metallic cations and emerging pollutants based on composite films of glycosaminoglycans.
Glycosaminoglycans are natural compounds that can be extracted from waste of marine origin and with chemical characteristics that make them attractive for use in different applications from health to the environment. These materials have a high solubility in water whereby, in order to be used as components of sensor elements, they must be immobilized in a compact and insoluble 3D structure. The strategy selected for this purpose was the chemical cross-linking of glycosaminoglycans with glutaraldehyde, epichlorohydrin, glycidyloxypropyltrimethoxysilane and tetramethoxysilane.

The team assembled for the implementation of this task has the scientific and technical skills to:
- production of glycosaminoglycans from marine wastes with characteristics suitable for their use in various areas (from health to industrial applications);
- production of composites using materials of natural origin;
- production and characterization of sensors and biosensors;
- assembly and sale of optical sensors