Bone Regeneration Solutions

The following technology elements play a part in the Bio-Inspire project
 

Cellnest Bio Material

Cellnest Recombinant Peptide based on human collagen type I

Over the past decade Fujifilm developed a range of unique new collagen-based biomaterials. Traditional collagen is derived from animal origin such as cow bones and pig skin. On the contrary, Fujifilm recombinant peptides (RCP) are produced by a yeast-based fermentation process. In this biotechnological process the yeast cells are modified to produce the RCP material in a consistent and reproducible manner. Like traditional collagen and gelatin, RCP consists of the characteristic collagen triplet amino acid base structure (Gly-X-Y). As such RCP is equally biocompatible and degradable by the same enzymes. On the other hand the recombinant DNA technique allows adjustment of the amino acid sequence of the RCP. Special functionalities can easily be added, such as additional cell binding sites (RGD) or increased number of (electrical charging) amines.

Cellnestpicture 













Download the Cellnest Brochure





Growth factors

Growth factors

A growth factor is a naturally occuring protein, that typically acts as signaling molecule between cells. Most of them act by binding to specific receptors on the surface of their target cells. Thereby they will activate pathways that will stimulate cell proliferation, cell differentiation or production of extracellular matrix. The specific action will vary between growth factors. For example, bone morphogenic proteins stimulate bone cell differentiation, while vascular endothelial growth factors stimulate the growth of blood vessels. However, the specific action of a certain growth factor will also depend on the target cell phenotype. Timing and interaction between growth factors is very important for a proper function.

Bio-mineralisation

New bio-inspired mineralisation processes

The structure of most animal organisms is characterised by the coexistence of three-dimensional organic matrices and nanostructured, well-ordered inorganic phases. Phase nucleation and growth on the matrices occur during a process know as "biomineralisation". This proces is strictly controlled by chemical, physical, and structural mechanisms. Through such processes, natural organisms form highly organised structures devoted to their sustainance and/or physical protection. These structures, like for instance skeletons, are characterised by high resistance, lightness and the ability to continuously adapt to ever variable external stimuli, to remodel and to self-repair. Several control mechanisms regulate the formation and organisation of the mineral phase in such organisms and determine the complex microstructure and functionality of natural mineralised structures.

The formation of bone takes place through a cascade of events that yield the self-assembling and organisation of collagen molecules into 3D fibrous matrices and, simultaneously, the heterogeneous nucleation of hydroxyapatite crystals on specific crystal sites of the assembling collagen molecules. The final construct, i.e. what is known as "woven bone", is characterised by a complex structure that is then remodelled into the final bone structure. In-lab mineralisation is carried out by reproducing the same thermal and chemical environment where the formation of new bone takes place. This generates highly complex 3D constructs mimicking the newly formed bone and exhibiting very regenerative behaviour.

Cell therapy

EPC's and MSC's

Mesenchymal stem cells (MSC's) isolated from bone marrow have been used successfully for the repair of bone defects. Several sources to isolate EPC are described in literature, but the bottleneck for using these cells in therapies is still the expansion capacity and the application of these cells. The major objective is to isolate and cultivate EPC's and MSC's. The focus is on establishment of methods to isolate endothelial progenitor cells (EPC's) from peripheral blood or from blood outgrowth endothelial cells (BOEC). There is another focus for the isolation and expansion of MSC's. The technique and culture conditions for MSC expansion play an important role for the maintenance of their differentiation potential. Additionally the functional characterisation on histological and molecular level is to be standardized. In this context a defined, serum-free medium for the expansion of endothelial cell and for MSC's needs to be established.

Partners

Bone Therapeutics SA

Erasmus Medical Center

Fraunhofer Institute

Fujifilm Manufacturing B.V.

Medicyte

ISTEC - CNR

University of Bologna

Marie Curie Actions

Logo Marie Curieeu logo
The research leading to these results has received funding from the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement n° 607051.