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The emergence of nanotechnology can enable development of entirely new classes of bioactive devices that need precise intracellular delivery for more efficacies and less toxicities. While both organic and inorganic technologies are under development, controlled-release polymer technologies will likely continue to have the greatest clinical impact for the foreseeable future.

Engineering smart materials allow for novel medical therapies such as designing smart implant based drugs that target cells with improved specificity, resulting in decreased side effects for patients. Other advances are being made in sophisticated biomaterials for use in surgical implantations that are less invasive, leading to shorter recovery times and decreased risk of postoperative infections or other complications. Such innovations will improve the quality of life, extend life expectancies, and could reduce the overall cost of healthcare. Biomaterials play central roles in modern strategies in regenerative medicine and tissue engineering as designable biophysical and biochemical milieus that direct cellular behavior and function.

Scientific scope of the UMR 1260

The INSERM-UNISTRA UMR 1260 “Regenerative Nanomedicine” affiliation is ITMO Technology for Health.

Tissue engineering, drug delivery, therapeutic discovery and engineering living materials research program in the UMR1260 aim at developing new approaches to repair, restore or regenerate tissue function lost due to injury, inflammation, chronic diseases, and aging.

The projects in UMR 1260 require a strong interdisciplinary work, involving transition from basic to translational research for understanding of disease mechanism, validation of therapeutic drug and delivery, biomarker discovery, and development of precision medicine in clinic. We use state-of-the-art-technologies such as nanomedicine-smart material, medicinal chemistry-drug discovery, pathway analyses-omics, 2D-cells and 3D-organoids models, as well as mice models of diseases, and formulations able to target the bioactive molecules or drugs.

Our ultimate goal is to improve the quality of life, extend life expectancies, and reduce the healthcare burden.

The scientific interests of our team focus on the questions related to innovations in the biomaterial, tissue engineering and therapeutic approaches in regenerative nanomedicine that are linked to 4 main programs:

Development of Advanced Therapy Medicinal Products (ATMPs), extracellular vesicles and stem cell-based strategies in regenerative nanomedicine
Development of novel therapeutic approaches to regenerate/restore vascular and metabolic organ function in diseases
Development of double 3D active implants equipped with well-organized cell organoids for neovascularisation to mimic tumor and to restore tissue
Development of innovative formulations allowing to improve the inherent biopharmaceutical properties of bioactive molecules or drugs. Use of biomaterials such as polymers, lipids are of particular interests to conceive original formulations with improved biopharmaceutical characteristics

Our challenge is to develop a novel generation of smart hybrid materials combining nanostructures, extracellular vesicles and stem cells « living materials » and to use them for clinical applications (bone; cartilage; teeth; cardiovascular and metabolic tissue repair and regeneration; tumor).

We specifically aim at:

i) Developing an innovative pharmacological treatment of periodontal and oral bony defects and identifying mechanisms of dental primary failure of eruption (PFE) and bone regeneration;
ii) Optimizing an innovative delivery approach capable of enhancing compound anti-inflammatory effects;
iii) Developing a more isomorphic mouse model of intra-oral implant (molar extraction-immediate
implantation), based on the collaboration between industrial partner Straumann;
iv) Targeting endothelial senescence and dysfunction to rejuvenate vascular and cardiac health in ageing and cardiovascular diseases;
v) Characterizing molecular mechanisms of microvesicles-driven accelerated senescence of endothelial cells to identify new targets and protect or rejuvenate endothelial cells in cellular models of transplantation mimicking the inflammatory-driven vascular response;
vi) Optimizing an innovative micro/mesofluidic physiological device based on vascularized and perfused organoids for a rapid and personalized therapeutic response;
vii) Establishing of preclinical models in cancer: patient-derived xenografts (PDX) and innovative 3D organoids for anticancer drugs testing, predictive biomarkers (therapeutic response, resistance) identification, and personalized medicine;
viii) Identifying new pathways and targets in anticancer treatment-mediated cardiovascular and metabolic toxicities, and developing new cardiovascular protective and anticancer drugs with less adverse effects;
ix) Developing innovative colloidal drug delivery systems based on lipids (nanoemulsions) and on polymers (rolled devices, transdermal devices, hydrogels).

We are also interested in vascular and organ dysfunctions in shock, rare diseases, pidemiology and public health; Medico economic evaluation of innovative technologies for health.

Our educational program emphasizes the use of molecular, cellular, ex-vivo and in vitro aspects of regenerative nanomedicine in the development of new biomaterials, innovative therapeutic approaches and new pathway identification from bench to sites with excellent technological platforms in CRBS.

The projects in UMR 1260 requires a strong complementary work, combining material science, medicinal chemistry, molecular and cellular biology and the clinic. Our activities concern domains such as:

1. Advanced Therapeutics for Bone and Cartilage Regeneration;
2. Anti-Inflammatory Therapeutics, Periodontal Regeneration and Dental Engineering;
3. Vascular Approaches for Tissue Repair in Organ Dysfunction and Graft Loss;
4. Innovative device to improve therapeutic treatment: Mesofluidic device;
5. Mesoscale organoids equipped with vascular and lymphatic network (healthy versus tumor);
6. Biogalenics and therapeutic innovations;
7. Medicinal Chemistry and regeneration of cardiovascular and metabolic tissues in cardio-oncology;
8 Precision Medicine; Rare Diseases & Public Health.

A technological platform is currently being set-up in the laboratory to handle all 2D and 3D models for cancer and other pathologies, for in and out activities, and including all necessary expertise and technical approaches, including cell and molecular biology, histology and in vivo experimentation.

Research topics

TOPIC 1: Advanced Therapeutics for Bone and Cartilage Regeneration (J. HUA / F. FIORETTI)

TOPIC 2: Anti-Inflammatory Therapeutics, Periodontal Regeneration and Dental Engineering (O. HUCK)

TOPIC 4: Vascular Approaches for Tissue Repair in Organ Dysfunction and Graft Loss (F. TOTI / L. KESSLER)

TOPIC 5: 3D Vascularized Strategies to Restore Healthy or Tumour organoids Microenvironment (G. UBEAU-SEQUIER / Y. IDOUX-GILLET)

TOPIC 6: Establishment of preclinical models in cancer : patient-derived xenografts (PDX) and innovative 3D organoids (T. MASSFELDER)

TOPIC 7: Biogalenic and therapeutic innovations (T. VANDAMME / N. ANTON / G. CONZATTI)

TOPIC 8 : Chemical biology and regenerative medicine in cardio-oncology (C. NEBIGIL / L. DESAUBRY)

TOPIC TR 1: Vascular and organ dysfunctions in shock (F. MEZIANI)

Topic TR 2: Rare Diseases , Epidemiology and Public Health (F. CLAUSS / A-M. MUSSET)

Technical platform: TiBioC Tissue Biofabrication and Characterization