Chemical functionalization of porous ceramics for application as new implant biomaterials
A promising approach to solve the problems associated with bone grafts and bone substitutes is tissue engineering, in which implants are seeded with biological components (for example, cells). In case of porous implants, bone ingrowth results in a mechanical attachment of the bone to the implanted material. We develop an interdisciplinary approach to define the characteristics of the biomaterials surface allowing the adhesion and survival of vascular cells and to promote further colonization of the biomaterials by cells of the tissue to rebuild bone structure.
Development of functionalized nanoparticles for theranostic applications
In vivo imaging has huge potential as diagnostic and prognostic tools in human diseases. We are pursuing the development of a novel generation of multimodal nanodevices capable of acting simultaneously as contrast agents for different imaging techniques (optical microscopy, magnetic resonance) and of complementing these imaging capabilities with other functions such as drug delivery, electric and pH sensing, etc.
To achieve multi-modal probes for long-term imaging, we develop chemical functionalizations of Second Harmonic Generation nanoparticles (SHG-NPs) for the selective binding to human disease biomarkers (cancer biomarkers and cellular structures reporting the presence of tumour cells or tumour-associated cells with defined characteristics of the tumour environment). These nanomaterials are also designed to display the possibility to be internalized by tumour cells or tumour-associated cells, in order to report over time of the loss, or maintenance, of these cells in a defined location in response to a therapy. Several efficient synthetic routes have been implemented for the preparation of PEG-based coating polymers and their covalent conjugation to targeting for specific association with cancer cells biomarkers.
In addition, we recently disclosed the possibility to use SHG-NPs as photo-therapeutic agents for in situ generation of UV. These results highlighted, for the first time, the use of up conversion NPs for on-demand and localized induction of direct damages on cancer cells nuclear DNA, paving the way for the development of theranostic devices based on SHG-NPs.
Development of functionalized polymeric hydrogels for cell immobilization
The increasing incidence of age-related diseases and the low availability of human donor material to replace dysfunctional cells and damaged tissues in patients have prompted the search for alternative transplantation therapies. Hydrogels, presenting a three dimensional (3D) structure, can serve as scaffolds for tissue engineering and as carrier for cell encapsulation and drug delivery. The transplantation of encapsulated cells/tissues prevents adverse immunological response while allowing the crossing of oxygen, nutrients and secreted factors. Despite the highly promising studies that have been directed toward the development of hydrogel microcapsules for the treatment of human diseases including liver failure, diabetes mellitus, Parkinson’s disease and anemia, routine clinical application of cell microcapsules still remains a challenge.
We develop synthetic routes for the production of PEG-grafted alginate hydrogels which are further conjugated to anti-inflammatory agents and drug scaffolds targeting fibrotic pathways to provide highly biocompatible materials for the encapsulation of islets and hepatocytes.
In vitro and in vivo evaluation of the resulting microcapsules, in collaboration with the University Hospital in Geneva (Prof. Léo Bühler) will address the long term functionality and viability of immobilized cells.