Abstract: Following the pioneering work of Bisceglie on the immobilization of insulin producing cells1 and the concept of "artificial cells" introduced in 1964 by Chang,2 the immuno-isolation of endocrine cells into three-dimensional semi-permeable hydrogels has emerged as a promising strategy for cell-based therapies.3 Among the many polymers which have been evaluated for cell microencapsulation, the natural polysaccharide sodium alginate (Na-alg) emerged as the reference material for cell immobilization due to its fast gelation in the presence of divalent cations and its high cell compatibility and in vivo tolerance.4-6 Despite these promising properties, the transfer to clinical applications is hampered by the lack of durability of alg hydrogels in vivo,7,8 the shorage of human cell material suitable for transplantation and the frequently observed pericapsular fibrotic overgrowth following the transplantation of alginate-based microencapsulated cells.9 We herein present several strategies aiming at maintaining the favorable properties of alg hydrogels while improving their stability in vivo by covalent conjugation of the hydroxyl groups of the alg backbone to cross-reactive poly(ethylene glycol) derivatives providing reinforcement of the hydrogel ionic network by covalent crosslinking interactions.10,11 Our recent approach for the controlled delivery of anti-inflammatory agents from the encapsulation matrix will be presented in the context of the transplantation of insulin producing cells, resulting in the mitigation of adverse fibrotic response.12 The development of porcine cell batches as alternative cells source for transplantation will also be discussed.

Keywords: alginate, cross-linked hydrogel, drug eluting hydrogel, cell microencapsulation, fibrotic overgrowth, cell transplantation.

Acknowledgements: The authors acknowledge the financial support from the Swiss National Science Foundation (Grant N° 310030E-164250) and the Foundation Insuleman.

Biography: Sandrine Gerber is, since 2007, Deputy Director of the Institute of Chemical Sciences and Engineering (ISIC) and Head of the Group for Functionalized Biomaterials (SCI-SB-SG) at the Ecole Polytechnique Fédérale de Lausanne (EPFL, Switzerland). She also serves as Adjunct Professor and Lecturer in EPFL's School of Basic Sciences. Prof. Gerber has solid broad knowledge in synthetic organic chemistry for the design and preparation of complex bioactive molecules. Her scientific expertise is related to the development of new chemical entities for bio-applications. The research activities of her group focus on the design, synthesis and evaluation of functionalized nanomaterials and biomaterials for therapeutic applications as bone implants, cancer imaging probes and cell transplantation devices. As part of her management function in ISIC (750 collaborators over two sites in Lausanne and Sion), Prof Gerber has direct supervision of analytic platforms, support services and workshops of the Institute. Her duties also include teaching of organic chemistry at the Bachelor and Master levels for the Section of Chemistry and Chemical Engineering at EPFL and the School of Biology and Medicine at the University of Lausanne (UNIL). She manages several independent national and international multidisciplinary scientific projects and was principal investigator in the European Commission FP7 NAMDIATREAM project (EU NMP4-LA-2010-246479). Sandrine Gerber received several awards for her research work, including the 2010 Werner Prize from the Swiss Chemical Society, and the 2018 Excellence in Teaching Award of the Section of Chemistry and Chemical Engineering. She is member of the Board of Directors of the Swiss Chemical Society and member of the Committee of the Doctoral Program of Chemistry and Chemical Engineering at EPFL.
Previously, she was post-doctoral fellow and scientific collaborator in the Institute of Organic Chemistry at the University of Lausanne, which merged with the Chemistry Department of EPFL in 2001. At that time, she developed total synthesis of natural products with particular focus on antibiotic and anti-cancer macrolides. She holds a PhD in Organic Chemistry and the habilitation from the University Pierre et Marie Curie (Paris VI, France).