The Biomaterials Federation of the North of France

The Federation Biomaterials has been founded in 1993. It is a grouping of research laboratories implicated in the biomaterials research and associated to industrial companies and clinical teams. The initial objective was to bring together partners all interested in the thematic of biomaterials, to give a structure to this grouping, to create an interdisciplinary network, to elaborate a common culture and common means of communication, and to define synergic actions. Briefly said: we wanted to make work together dispersed laboratories and to create a pluri- and interdisciplinary research cooperation in the domain of biomaterials.

The Federation is chaired by a scientific board, which is the organ of decisions and which meets once every month since 1993. This committee defines and evaluates the scientific themes, decides the actions of scientific manifestations to undertake, and coordinates the divers activities. Several External Scientific Councils have already underlined the originality and the interest of such a federative enterprise.

Fourteen years later, in 2007, the Federation is composed of a dozen principal research teams belonging to 5 regional Universities and Engineering Schools. It holds an active cooperation with several regional and national companies, and it includes high-level clinical teams. The teams practice excellent cohesive and transversal collaborations with a strong a pluri- and interdisciplinary dynamic. The Federation has already organized or co-organized multiple national and international meetings with specific scientific themes. The structuring character of the Federation is validated since its foundation by the progressive integration of numerous new teams and the enlargement to European and international Cooperation.

From 1993 to 2007, the actions of the Biomaterials Federation have been supported by the Regional Department of Research and Technology and the national Ministry of Research and Technology, by the Regional Council, by the European Union (FEDER), by the National Agency of Research (ANR), by the CNRS and INSERM, by the Pasteur Institute of Lille, and by private companies..

The strength of the Federation is based on the conception, elaboration, characterization, evaluation and fabrication of implantable functionalized medical devices with modulated and controllable biomedical activities. These new medical devices can be used for bone substitutes, and/or in a larger sense for vascular prostheses and endovascular devices, for guided tissue regeneration (GTR) in dental surgery, and for abdominal and intraperitoneal plates and meshes as tissue scaffold implants.

The Biomaterials

The living standard of industrial countries does not only increase the life span but also the prevalence of certain deceases. In addition, the populations support less and less easily the restriction of physical possibilities and of resulting handicap. To treat or replace an organ or its function, biomaterials, i.e. implants and prostheses, take an increasingly important place in the treatment of deceases respective to nearly all medical disciplines.

Several facts may foresee a strong amplification of this phenomenon, in particular in the field of functionalized medical devices, which is a very huge pluridisciplinary and little explored domain. At our days, the tendency of international research is not longer the substitution of an organ by Inert and biocompatible biomaterials, but the research of functionalized medical devices adapted to the implantation site, which can find therapeutic and medicamental applications.

We assist to the arrival of a new generation of biomaterials with much higher potentialities. This evolution is characterized by less mechanical approaches (osteosynthesis material, articular prostheses, vascular implants, conduct replacements), which become more and more biological: growth factors, cytoconducting proteins, cell adhesion enhancing molecules, cell therapy, biotechnology, gene therapy, etc. These tendencies generate not only consequences on the public health, but may have strongly considerable economic repercussions. It is related to the patient costs loosening their autonomy, the proper costs of the biomaterial, and to the perspectives of the development of new biotechnologies. Prospective studies consider a period of only some years for when the market of new biomaterials will overcome the market of classic biomaterials

Innovation: Functionalization of Implants and Prostheses

Economic Context and Stakes

The interest of this evolution is essentially in the development of new types of functionalized implants and prostheses by divers chemical surface treatments able to prevent pre-, peri- and postoperatory infections, to improve their plasmatic compatibility, to stimulate tissue integration and/or to accelerate the time of healing for the patient. This presents an evident socio-economic advantage and an important added value for health economics.

Scientific Context

Over the last 15 years, biomaterial research is oriented to the activation of biomaterial surfaces in order to optimize the interaction in the interface between the material and the biosystem and subsequently the tissue integration of medical devices. At the present state-of-the-art, functionalization is turning around the grafting of polyacrylic acid or polyethylene glycol as spacer molecules for further binding of bioactive molecules such as growth factors, antibiotics, extracellular matrix constituents, and more specifically cell adhesion modulating molecules, but without any eminent progress.

Since now about 5 years several laboratories have enhanced their competences to develop new technologies in order to obtain biocompatible materials with functionalized surfaces. Several means are available in particular the grafting of bioactive molecules (i) via new spacer molecules to stimulate the target to go to the material surface, and (ii) via surface adsorbed molecules to provide controlled drug delivery systems. Most of these methods can be applied on all implantable materials, and they are in particular very useful and forthcoming for scaffolds, hybrid medical devices and tissue engineering. The last few years, a great progress in the functionalization of biomaterials was achieved by the huge development of nanosciences applied to the nanostructuring of the material surfaces.

Consequently, this latter field and the domain of biological and molecular surface coating are well represented in the Federation, the aim of which is to strengthen scientific and industrial co-operation between technical, biological and medical domains. It subsequently attracted researchers from multiple disciplines such as material science and engineering, mineral and organic chemistry, (bio)physics, electro-chemistry, analytics, cell and molecular biology, pharmacology, medicine (orthopedics, dentistry, ophthalmology, cardiology, urology, visceral surgery) to achieve the improvement of interface interactions and subsequently of tissue integration of medical devices.

In addition to the above general aspects, specific areas are considered in the Federation which cover wide multidisciplinary fields such as surface tailoring; physical and chemical molecular grafting via spacer and/or cage molecules; covalent binding of bioactive molecules; controlled drug delivery systems; nanopaterning and nanostructured devices; interaction between biomaterials surfaces with bioactive molecules and living cells; improvement of tissue integration; improvement of cell adhesion by grafting of extracellular matrix constituents; Cytochemical immune-labelling of cytoskeleton, extracellular matrix, and focal adhesion contacts; pro-inflammatory markers; physical and chemical surface characterizations; endogenous biomimetic coatings in appropriate fluids.

 

Therapeutic Activities

Different techniques allow enhancing sensibly any therapeutic activity by grafting or complexing bioactive molecules. Two different basic principles exist:

  • Controlled Drug Delivery Systems: One can imagine the inclusion of bioactive molecules in surface coatings of implants with modulated liberation of the molecules. These can be integrated in the substrate itself and will become bioavailable during the dissolution or biodegradation of the substrate: e.g. collagen, bioglasses, resorbable polymers, etc. Or the bioactive molecules are complexed on grafted carrier molecules (spacers) and then delivered in the organism.

The principle of this system is that the bioactive molecule goes to the target. It allows controlling the delivery of antibiotics, growth factors and other active agents or drugs modulating a physiological process.

  • Immobilisation of bioactive molecules complexed directly on the substrate or covalently bound on grafted carrier molecules (spacers). The principle of this system is that the target goes to the bioactive molecule. – By these treatments, ceramics (as any other material) will become a highly interesting support for applications in the domains of cell therapies and tissue engineering: stimulation of tissue integration, scaffolds used for tissue engineering and reimplantation of hybrid mediacal devices. A functionalization of these materials may considerably accelerate in vivo and in vitro cell growth and subsequently the healing process.

Applications

The methods owned by the Member Laboratories of the Federation, we can graft different bioactive molecules on variable substrates used in nearly all medical and surgical disciplines: titanium alloys (stents, orthopedic implants, dental implants, etc.), polymers (vascular prostheses, plaques, meshes, urologic prostheses, GTR membranes, etc.), rubber silicones (catheters, tubes for secondary exits, transcutaneous devices, biosensors, etc.), certain ceramics (bone substitutes, etc.).

Lille, June 7, 2007