Animal tissues are an immense source of inspiration for humans which actually mimic (
biomimetic approach
) and use them for novel material design and production. Connective tissue is the most important animal structural material and it (or its components) is often used as sourse of inspiration/model for different applications. Its main extracellular matrix (ECM) component is collagen. Currently, industrially available collagen is mainly of bovine origin, that, however, carries a risk of transmission of serious diseases (BSE and TSE). Therefore, alternative and safer sources of collagen are required for regenerative medicine and one of the most safer and recently exploited source are aquatic organisms. The marine invertebrates we want to use in this project (echinoderms i.e. sea-urchins, starfish, etc.), possess peculiar and unique connective tissues, called Mutable Collagenous Tissues, which could actually represent an alternative source of collagen. Moreover MCTs undergo extremely rapid, drastic and reversible changes (completely indipendent from any muscolar contribution) in their passive mechanical properties such as stiffness, tensile strength and viscosity. Several evidences suggest that MCTs are probably one of the key elements of the striking regenerative capacities found in echinoderms, since they more or less directly help the regenerative process, providing optimal growth-promoting environment and “dynamic” structures for tissue repair and regeneration. MCTs could therefore represent a valuable source of inspiration for biomaterial design adressed to biomedical application. The biomimetic approach represents the new strategy pursued also in the field of human regenerative medicine. Nevertheless, existing biomaterials lack the inherent adaptability of natural tissues, in fact they do not mimic a structurally dynamic environment. Regenerating tissues, instead, are necessarily continuously dynamic environments: throughout the regenerative processes they have to constantly change both their mechanical and 3D structure as well as their composition. The regenerating tissue has to develop from a draft cell organization to a functional and well-defined structure. Incorporating to naturally derived (collagen made) scaffold the novel concept of dynamic self-assembly, learnt from natural models that already physiologically behave in this manner (MCTs), would constitute a radical step beyond the existing intelligent matrices for tissue engeneering and an important progress towards more physiologically-responsive biomaterials for regenerative medicine.
The very ultimate challenge of the project is to explore the possible development of a new class of biomimetic materials inspired to echinoderm MCT to be used for scaffolds for tissue regeneration/cell colture studies. The
first main general aim
of this project is to acquire the appropriate information on the model we want to get inspiration from (MCTs) i.e. to understand how natural MCTs actually work. The development and assembling of a simple biomaterial will be the
second general aim
to pursue with the final innovative perspective of developing a new biomaterial, designed at the nanoscale, simulating some MCT analogous properties. These new materials should be able to reversibly change their mechanical characteristics and structural integrity following 1) external manipulation or 2) more challanging but very long-term, according to the
in situ
physiological requirements of the surrounding growing tissue (i.e. the tissue it self modulates the structural integrity of the scaffold through specific cellular signals). The whole research work will be developed according to the following
specific objectives
:
1.to define the basic biology of natural MCTs, particularly the key-components, their fundamental interactions and their evolutionary pathways, this will be achieved through morphological, biochemical, biomolecular and biomechanical characterizations;
2
. to find a new alternative and safe collagen source: the obtained collagen will be used for the development of a first-level biomaterial, a very simple collagen scaffold (biofilm) for cell colture; 3. to develop a new (second-level) biomaterial simulating natural MCTs. Since reproducing the complex natural structure of MCT is virtually impossible, we will start manipulating simpler components in order to produce a composite with tuneable mechanical properties and whose biocompatibility will be tested in cell colture studies.
The proposed project has a wide potential impact and scientific/technical benefits in different scientific fields, including animal biology, engineering and biomedicine. The idea of a dynamic scaffold capable of adapting its stiffness/structural integrity according to the needs of a growing tissue is a radical concept which may chance the scenario of intelligent materials for Tissue Engineering. Manipulation, at nanoscale level, of MCT-derived or MCT-inspired components, used as building blocks of extracellular matrix analogues, will open new horizons for a variety of tissue regenerative therapies. Furthermore, inthis project we will test and develop a new collagen source (sea urchin collagen), economically very advantageous since obtained from “waste material” of the sea urchin food industry. Regarding animal biology, we expect to come to an exhaustive and still lacking MCT characterization in terms of morphology, biochemistry, physiology, biomechanics, molecular biology and evolution. Overall, combining different disciplines this multidisciplinar project will certainly provide a broad spectrum of new knowledge. Experts of echinoderm functional biology (UMIL) will join here experts in biomaterial design (INEB) to guarantee the final success of the project. Historically, when such different disciplines as biology and material engineering have met, the obtained results have been outstanding (shark-inspired swimwear, gecko-inspired medical adhesive).