In the early 1990s, I embarked on my PhD journey at the Department of Radiology and Radiotherapy at the Radboud Academic Hospital in Nijmegen, the Netherlands. There, I spearheaded the development of protocols for noninvasive analysis of the bioenergetic and perfusion status of gliomas using magnetic resonance spectroscopy and imaging. These pioneering studies helped future radio- and chemotherapy protocols for patients. During my Post-Doc tenure at the Utrecht Academic Hospital, I continued similar research, but with a focus on cerebral ischemia. These experiences paved the way for a permanent research position at INSERM (National Institute of Health and Medical Research) in France.
My initial research projects in France centered on the utilization of MRI and intravital microscopy to analyze the effects of novel radiotherapy protocols on normal brain tissue, including the vasculature, and gliomas. This work aimed to optimize new radiotherapy protocols to spare normal tissues while enhancing damage to gliomas. During this period, my interest in intravital microscopy grew, leading to the establishment of a national platform as scientific director in 2007 at the Institute of Neuroscience in Grenoble. Through this platform, I fostered collaborations with scientists working on new nanotechnologies for brain tumor diagnosis and treatment.
In 2013, I assumed the role of director of a research group at Clinatec (CEA-Tech Grenoble), focusing on exploring nanotechnologies for the detection and treatment of glioma recurrence in resection cavities. For recurrence detection, we delved into new optical imaging methods such as photoacoustic microscopy and imaging. Treatment strategies were based on innovative photodynamic therapy protocols. Unfortunately, in 2017, INSERM and university scientists were dismissed from Clinatec due to a senseless dispute between our institutions.
In 2019, I joined the permanent faculty at the TIMC institute in Grenoble, as part of the SyNaBi research group, which specializes in implantable medical devices capable of interacting with the body. In this capacity, I leverage my intravital microscopy platform to develop new inflammation imaging methods for biocompatibility testing of medical devices in vivo. Additionally, I explore novel smart matrices for cell therapy applications, integrating optical biosensors to monitor the viability and maturation of implanted cells in vitro and in vivo. These applications include artificial pancreas, skin, and in vitro companion diagnostic devices in (neuro)oncology.
The SyNaBi research team at TIMC leverages its core expertise in electrophysiology, biophysics, neutron and X-ray scattering, bioelectrochemistry, intravital microscopy, biopolymers, drug delivery, and cell/molecular biology to develop various types of medical devices.
My primary research focuses on cell therapy applications, such as artificial pancreas and skin. In collaboration with chemists from the interdisciplinary physics lab (LiPhy), we photopolymerize gelatin (GelMA) matrices using digital light processing or two-photon polymerization for the macro-encapsulation of pancreatic islets and large skin wound dressings. These matrices include bio-optical sensors for monitoring cell metabolism locally before and after implantation. As the scientific director of an Intravital Microscopy Platform (GiS-IBiSA and France Life Imaging) at the medical faculty of the Grenoble Alpes University, I have easy access to two-photon and photo-acoustic microscopy (LiPhy) for optimizing cell therapy protocols both in vitro and in vivo.
One of my roles in the SyNaBi team is to analyze the stability and biocompatibility of new devices in a transgenic mouse model that expresses eGFP in mononuclear phagocytes. In this model, inflammation processes and their treatment can be tracked over time on a microscopic scale. It is crucial to prevent chronic inflammation and fibrosis formation around implants, as these conditions can hinder biochemical and cellular exchanges with host tissues.
1. Sanden B Van Der, Gredy L, Wion D, Stephan O. Acta Biomaterialia 3D two-photon polymerization of smart cell gelatin – collagen matrixes with incorporated ruthenium complexes for the monitoring of local oxygen tensions. Acta Biomater. 2021;130:172–82.
2. Menassol G, Sanden B Van Der, Gredy L, Arnol C, Divoux T, Martin DK, et al. Gelatine–collagen photo-crosslinkable 3D matrixes for skin regeneration. Biomaterials-science. 2024;12:1738–49.