Event Abstract Back to Event A self-setting and tunable injectable hydrogel biomaterial for cell therapeutic treatment of irradiated colon Girish Pattappa1, Gildas Rethore1, Lara Moussa2*, Fernando Sineriz3*, Marie Gilbert3, Stephanie Filipe3*, Denis Barritault3, Noelle Mathieu2*, Jerome Guicheux1 and Pierre Weiss1 1 University of Nantes, Centre for osteoarticular and dental tissue engineering (INSERM U791), France 2 Institution for Radiological Protection and Nuclear Safety (IRSN), Laboratory of Research in Regeneration of Irradiated Tissues, France 3 OTR3, Research and Development, France Pelvic irradiation is used to treat malignant tumours, however healthy surrounding tissues can be damaged by ionizing radiation, leading to chronic gastrointestinal complications, which affect quality of life with substantial mortality. Stem cells injected into the damaged area helps restore tissue function through release of angiogeneic, pro and anti-inflammatory molecules, collectively described as the secretome[1]. However, multiple injections are required due to cell death at injection site. Biomaterials may be used to enable a single injection, protecting cells from host tissue environment, whilst maintaining cell viability and function. A silanised hydroxypropyl methylcellulose (Si-HPMC) hydrogel has been designed within our lab for injectable cell delivery[2]. Thus, the aim of this investigation was to combine these technologies for the development of an injectable biomaterial for stem cell therapeutic treatment of irradiated colon. Materials and Methods: Si-HPMC was synthesized and hydrogel formulated as described2. Rheological measurements (viscosity, gel-point. elastic modulus (G’)) were performed at a range of Si-HPMC concentrations (0.6 – 2%) that could be injected through a specific catheter into the colon lumen. Rat adipose stromal cells (ASCs) were seeded into the hydrogel (1.5% Si-HPMC + 3.33 x 106 cells/ml) and cell viability assessed on day 1, 7, 14 and 21 during culture. On day 6 and 20 during culture, cells were cultured in a-MEM without FBS and analysed for secretomic molecules using ELISA assays for rat ASCs. In parallel, human ASCs were seeded at 2 x 106 cells/ml within the same construction and assessed for the same parameters with Luminex assays used for analysis. Figure 1, The (a) gelation time and (b) elastic modulus (G') for Si-HPMC at variable concentrations. Images of stem cell-Si-HPMC hydrogel construction injected into irradiated colon stained with PCNA staining following 7 days culture within tissue at (c) x5 and (d) x10 magnification. Results and Discussion: Viscosity and G’ increased and gelation time decreased with increasing Si-HPMC concentration, demonstrating the tunable properties of the hydrogel (Figure 1a and b). Following 21 days in vitro culture, rat and human ASCs were 70-80% viable within the hydrogel construction, Supernatant analysis indicated that cells were able to secrete angiogenic, chemoattractant and anti-inflammatory molecules during the period of culture. Additional in vivo analysis confirmed that the described construction was able to restore intestinal function due to secretion of these molecules (Figure 1c and d). Conclusion: ASCs encapsulated within a injectable hydrogel hydrogel has the ability to act as a cell therapy for treatment of irradiated colon. Furthermore, the use of biomaterial-assisted cell therapies can be used in the treatment of other pathologies, e.g. osteoarthritis. ANR, ANTHOS grant