Thematic research areas

Biomaterials have been and still are a key issue in the development and marketing of medical devices. Examples include the fields of osteosynthesis (bone fixation), orthopaedics (hip and knee joints), spinal reconstruction, dental implants, minimally invasive surgical devices, contact lenses, cardiovascular surgery (vascular prostheses, pacemakers, cardiac valves, stents), wound healing applications (sutures, staples, and adhesives), tissue regeneration, regenerative medicine, contact lenses, and others.

Implanted medical devices, despite notable contributions to patient quality of life, present enduring challenges in vivo.  Blood coagulation, erosion, infection, complement activation, foreign body reactions, aseptic loosening and mechanical figure prominently in certain device failure modes.  All of these adverse events are interfacial in nature: the host tissue-implant interface with the implant produces problems that compromise performance.  Device surface modification (e.g., coatings, thin films, topography, chemistry, etching) has been traditionally exploited to improve this interface, however with limited success. Such strategies still hold promise in many device markets but do not represent “one-size fits all” solutions.  Combination devices – those comprising functional peptides or proteins or drug releasing components on-board of functional prosthetic implants or degradable tissue-specific functions – represent a versatile and emerging clinical technology promising to provide desired performance improvements to implant devices. Functional failures of implants and devices are often related to inadequate interface interactions based on a non-physiological implant material behaviour. Nonlinear material properties may contribute to mimic natural tissues. Infection and sustained inflammatory responses are processes that often severely reduce the success rate of implantations and are the cause of very substantial health care costs. Recently, new antimicrobial and anti-inflammatory agents have shown promising effects, but their effective combination with biomaterials/implants and surfaces requires further development and testing under clinically relevant conditions. Most prominent are new combination devices representing current bone-related and cardiovascular implants with new added capabilities from on-board or directly associated drug delivery systems.

• Colored Ceramic Surfaces for Metallic Dental Implants and Prosthetic Appliances - Project approved, to start in 2010
• Low wear articulating implants employing DLC coatings on CoCrMo and TiAlNb with predictable, long-lasting coating adhesion lifetime - Project approved, to start in 2010
• Fibroblast Growth Factor 2 delivery for tissue repair: From Natural Concepts to Engineered Systems - Project approved, to start in 2010

Biomaterial-centred and medical device-related infections and sustained inflammation are a major health care problem today with an adverse impact on the quality of life of patients, prolonged hospital stays and high costs. One reason of implant infection is the combination of primary infection during surgery or contamination in the event of a trauma with the slow healing and insufficient integration of the implant material. Although progress has been made in recent years in the protective strategy for some medical device infection, the risk of implant-associated infection is still considerable with > 30% in open polytrauma fractures, 10-30% for cardiovascular systems, and 2-5% for orthopaedic devices. Furthermore, degradation products or substances released over long time periods of implanted devices may induce chronic inflammation or an undesirable immune response in a considerable number of patients.

Various surface modification strategies, particularly topographical and (bio)chemical ones, have been addressed in the past to reduce the risk of interfacial biofilm formation and infection and thereby prevent sustained inflammation at implant sites. Such approaches include (a) creation of surface properties that favour differential host cell attachment and device integration of implants over bacterial colonization and biofilm formation, increasing the chances of host cells to win the “race for the surface”. (b) The functionalisation of materials and surfaces with anti-microbial and/or anti-inflammatory components, either as “permanently” bound moieties or as controlled release systems.

More recently proposed research concepts aimed at overcoming some of the inherent drawbacks of current approaches, which are, for example, development of resistance, reduced activity when surface-linked, rapid loss of anti-microbial functionality as a consequence of, for example, dead bacteria debris contamination, or cell toxicity risk. Promising novel approaches include (i) Molecularly designed biocidal/anti-inflammatory drug release systems with a well controlled spatio-temporal release profile and/or exploiting a dual drug delivery strategy; (ii) The use of anti-microbials evolutionary developed by plants or animals, e.g., agents known to interfere with the bacteria’s quorum sensing mechanism, and anti-microbial peptides, for which development of bacterial resistance has rarely been reported; (iii) Strategies aimed at locally detoxifying implant surfaces or releasing substances in order to prevent development of chronic inflammation. Concurrently, there is an important need for more predictive, efficient and statistically significant assays compatible with bioactive interfaces, such as novel methodology based on the use of surface-functionalized, bioactive microparticles suspended in bacterial cultures combined with efficient readouts such as FACS.

• Biocompatible Films, Foams, Fabrics, and Surfaces from Poly(isobutylene)–Oligopeptide Conjugates - Project approved, to start in 2010

• Serrulatane-based  antimicrobial surface platforms - Project approved, to start in 2010

Drug delivery systems aim at administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals through a combination of properties such as drug release profile, distribution and elimination. Such techniques improve product efficacy and safety, as well as patient convenience and compliance. Administration methods include peroral, topical (through skin), transmucosal, inhalation and injection delivery. While certain delivery formats, e.g. transdermal, have successfully found its market, mostly for niche applications, the great market opportunities and technical challenges in this field are still awaiting the development of designed delivery vehicles that allow for efficient transportation in the body to the target tissue/organ with minimum adverse side effects, and controlled spatio-temporal drug release profile at the target site. This is in strong contrast to the current practice of continuous and systemic release.

Smart packaging and drug-(bio)polymer conjugation are particularly important aspects in oral administration of “difficult” drugs, such as water-insoluble molecules and highly cell-toxic anti-cancer drugs, for difficult-to-target diseases such as metastatic and brain tumours, and generally for delivery of modern pharmaceutical proteins, peptides and antibodies. Another promising field is modern immunotherapy strategies, for example exploiting efficient targeting of lymphatics and draining nodes/dendritic cells by ultra-small, antigen-bearing, intradermally injected nanoparticles (the latter concept successfully developed with CCMX support in the period 2006-09). From an industrial perspective, novel delivery formats have the capability of improving drugs already on the market, preventing candidates from falling out of the product pipeline, or making use of developed drugs of high efficacy but also high toxicity. It is furthermore widely believed in our community that such difficult-to-administer bio(macro)molecular drugs, and biologics in general, are going to comprise an increasing proportion of the new-drug market. Finally, novel and proprietary dosage forms may constitute a way for continued protection of drugs coming off patent, as well as an opportunity for the future development of a generic industry in analogy to the one that evolved from the development of small molecule drugs.
For quite some time, the focus in both academia and industry has been on applying existing materials for use in drug delivery applications, i.e.: materials that have already cleared regulatory hurdles in the US FDA and the European EMEA.  This approach, which focuses on materials processing rather than new materials chemistry, has led to very limited progress and limited translation to clinical impact.

Therefore, this thematic area  will focus on the development of novel materials for drug delivery designed at the molecular level and with the envisaged therapeutic pathways in mind, i.e.: materials that can display a novel function and yet are designed to exhibit biocompatibility and favourable toxicology.  The novel functionality of these materials could be in efficiency of processing, fidelity of nanomaterial fabrication, improved drug loading capacity, extra-long circulation time, targeting of particular tissue sites such as inflammation of tumour vasculature or lymph nodes, targeting of particular cellular domains, or delivery of difficult-to-handle drugs. Materials designed for any class of drug that meets a clear clinical need are appropriate. Novel chemical structures, designed at the nano and molecular scale, for example intelligent materials that efficiently and specifically release a drug in a controlled fashion in response to stimuli, externally or biochemically triggered, are a plus, especially with support of the proposed design from the literature or from preliminary data.  As such, this portion of the call focuses on chemical creativity and novelty of design, yet with a clear prospect for propensity for translation to animal research and ultimately human medicine.Biomedical imaging: With regard to imaging, material-sensitized contrast enhancement in any imaging modality is desired, e.g., novel magnetic materials (composition, shape) with improved magnetic properties/contrast, sufficient circulation time and favourable toxicity data for application in magnetic resonance imaging (MRI), or optically active constructs with improved stability, penetration depth and/or level of contrast. A further important criterion refers to the degree of resolution and the envisaged ability to detect very small malign structures by imaging, for example the diagnosis of developing metastasis or the initiation of tumour growth.  We particularly encourage submission of proposals where structured nanomaterials are to be developed that will be capable of fulfilling more than one function for in vitro and/or in vivo applications, e.g.: (a) Creative designs of multi-functional and smart materials that, for example, enhance contrast in more than one imaging modality; (b) Nanoparticles with well-defined size and shape that present biochemical cues for targeting specific cells/tissue, e.g., in the context of diagnosis of cancer or cardiovascular diseases such as early stages of atherosclerosis; and (c) Constructs combining targeted imaging with triggered release and therapeutics are in particular demand (“theragnostics”).

• Structural evolution and rheological properties in gel carrier - Project approved, to start in 2010

Products containing nano-objects (nanoparticles, nanotubes, nanofibres, nanorods, nanoplates and other nanostructured materials) are considered to provide benefits to society and opportunities for more efficient usage of natural resources and improved protection of the environment. Such materials have already been introduced in several market sectors such as health care (drug delivery, regenerative medicine, and diagnostics), cosmetics, textiles, electronics, information and energy technology, and environmental protection.

Given the rapid evolution of nanotechnology, mass production of nanomaterials will soon become standard implying also potential wide-scale exposure of workers and consumers as well as the environment. Several countries (e.g. USA, Germany, Switzerland, Japan) as well as the European Union have set up a „Strategy and Action Plan“ for nanosciences and nanotechnologies: This has been put into place in order to foster potential benefits of nanotechnologies, but in a safe, integrated, and responsible way. Switzerland started already in 2008 with the implementation of the actions defined in this strategy and several programs will be realised within the coming months. One of the main programs has been established by the BAG (Federal Office of Public Health), the so-called „Vorsorgeraster“, by which companies can evaluate their production processes and are advised on further activities to protect their workers or the environment against release of nano objects or the exposure to nanomaterials.

Within the context of the international co-operation for the safety of nanotechnologies, especially with respect to activities of the OECD and standardisation in ISO/CEN, the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) of the European Commission defined in its latest report on „Risk Assessment of Products of Nanotechnologies“ (2009) the following priorities:

1. Optimisation of existing and/or development of new test methods, in vitro and in vivo, to address aspects specific to engineered nanomaterials in characterisation and hazard assessment.2. Improvements in exposure assessment including, among others, relevant information on sampling, detection, instrumentation and modelling.

With this background, CCMX will support activities focussing on the development and establishment of standardised methods for in vitro and in vivo investigations of biological effects of nanomaterials. Availability, through dedicated synthesis, of well defined and quantitatively characterised nanoparticles with precisely tailored physical and chemical core and surface properties are a key requirement. Moreover, personalised measurement devices of nanoparticle exposure at the workplace is of interest as well. This program is complementary to the NFP 64, which addresses the fundamental biological mode of action of nanomaterials whereas CCMX focuses herewith on the development of standardised methods.

• V.I.G.O. - a new evaluation tool for determination, description and comparison of the biological effects of nanoparticles/nanomaterials  - Project approved, to start in 2010