G.A. nr 825159 – Duration 1/12/2018 – 31/07/2020 – Funded by ERC-PoC-2018
Miniaturised optically accessible bioreactor for drug discovery and biological research.
NEW Video with project results (relevant publications are linked at the bottom of this page)
The problem that we address is that the pharmaceutical companies do not develop radically new drugs anymore, because the development process lasts ten years and costs around one billion euro. Development of a new drug is subjected to regulatory approvals following three demonstrations: lab discovery in vitro, animal testing in vivo and clinical trial on patients. This process has 99.9% overall failure, of which 96.4% because the drug efficacy measured in vitro is not confirmed in animals.
In fact, the most widespread technology used to test therapeutic agents in vitro, a flat culture dish in which single cell populations are cultured and the drug to be tested is added to the culture, is obsolete. In many pathologies such as cancer and neurodegeneration, in vivo response to drugs is based on complex interactions, occurring in three-dimensions (3D) between several cell populations.
To solve this problem, in the context of an ERC consolidator grant (CoG) that I currently lead, I integrated a novel nano-patterned 3D substrate for stem cell culture, called the “nichoid”, into an existing miniaturised optically accessible bioreactor (MOAB). The MOAB allows to culture 3D organoids of few millimetres in size, under continuous perfusion of the culture medium, infusion of the drug to be tested and diagnostics of cell response both in real time and also post-cultivation. Both the original inventions (the nichoid and the MOAB) are covered by Italian patents originated in the frame of the CoG project and already extended as PCT.
The goal of this PoC proposal is to perform a technical and commercial feasibility to move to the market the MOAB device integrating the nichoid-patterned substrate. I will characterize the fluid-dynamics of the bioreactor chamber that has been modified to accommodate the nichoid substrate. Also, I will set a market assessment and an actionable IPR strategy with identification of a suitable exploitation strategy for valorising the patent/know how.
Laganà M, Raimondi MT. A miniaturized, optically accessible bioreactor for systematic 3D tissue engineering research. Biomedical Microdevices. 2012. 14(1):225-234, ISSN 1387-2176, DOI 10.1007/s10544-011-9600-0
Nava MM, Raimondi MT, Pietrabissa R. A multiphysics 3D model of tissue growth under interstitial perfusion in a tissue-engineering bioreactor. Biomech Model Mechanobiol 2013. 12(6):1169-1179. DOI 10.1007/s10237-013-0473-4, ISSN: 1617-7959
Raimondi MT, Giordano C, Pietrabissa R. Oxygen measurement in interstitially-perfused cellularised constructs cultured in a miniaturized bioreactor. J Appl Biomater Funct Mater 2015; 13(4): e313 – e319. doi 10.5301/jabfm.5000246
Credi C, De Marco C, Molena E, Nava MM, Raimondi MT, Levi M, Turri S. Direct photo-patterning of hyaluronic acid baits onto a fouling-release perfluoropolyether surface for selective cancer cells capture and immobilization. Mater Sci Eng C Mater Biol Appl. 2016 May; 62:414-22. doi: 10.1016/j.msec.2015.12.063
Tunesi M, Fusco F, Fiordaliso F, Corbelli A, Biella G, Raimondi M.T. Optimization of a 3D dynamic culturing system for in vitro modeling of Frontotemporal Neurodegeneration-relevant pathologic features. Frontiers in aging neuroscience. Front Aging Neurosci. 2016 Jun 22;8:146. doi: 10.3389/fnagi.2016.00146
Frattini P, Villa C, De Santis F, Meregalli M, Belicchi M, Erratico S, Bella P, Raimondi MT, Lu Q, Torrente Y. Autologous intramuscular transplantation of engineered satellite cells induces exosome-mediated systemic expression of Fukutin-related protein and rescues disease phenotype in a murine model of limb-girdle muscular dystrophy type 2I. Hum Mol Genet. 2017 Oct 1; 26(19):3682-3698. doi: 10.1093/hmg/ddx252
Marturano-Kruik A, Nava MM, Yaeger K, Chramiec A, Hao L, Robinson ST, Guo XE, Raimondi MT, Vunjak-Novakovic G. Human bone perivascular niche-on-a-chip for studying metastatic colonization. Proc Natl Acad Sci U S A. 2018 Feb 6;115(6):1256-1261. doi: 10.1073/pnas.1714282115
Izzo L, Tunesi M, Boeri L, Laganà M, Giordano C, Raimondi MT. Influence of the static magnetic field on cell response in a miniaturized optically accessible bioreactor for 3D cell culture. Biomedical Microdevices (2019) 20:29. https://doi.org/10.1007/s10544-019-0387-8
Steimberg, N., Bertero, A., Chiono, V., Dell’Era, P., Di Angelantonio, S., Hartung, T., Perego, S., Raimondi, M.T., Xinaris, C., Caloni, F., De Angelis, I., Alloisio, S. and Baderna, D. (2020) “iPS, organoids and 3D models as advanced tools for in vitro toxicology”, ALTEX – Alternatives to animal experimentation, 37(1), pp. 136-140. DOI https://doi.org/10.14573/altex.1911071
Raimondi MT, Donnaloja F, Barzaghini B, Bocconi A, Conci C, Parodi V, Jacchetti E, Carelli S. Bioengineering tools to speed up the discovery and preclinical testing of vaccines for SARS-CoV-2 and therapeutic agents for COVID-19. Theranostics 2020; 10(16):7034-7052. doi:10.7150/thno.47406. Available from: doi:10.7150/thno.47406
Parodi V, Jacchetti E, Bresci A. Talone B, Valensise CM, Osellame R, Cerullo G, Polli D and Raimondi MT. Characterization of Mesenchymal Stem Cell Differentiation within Miniaturized 3D Scaffolds through Advanced Microscopy Techniques. Int. J. Mol. Sci. 2020, 21, 8498; doi:10.3390/ijms21228498
Remuzzi A, Bonandrini B, Tironi M, Longaretti L, Figliuzzi M, Conti S, Zandrini T, Osellame R, Cerullo G, Raimondi MT. Effect of the 3D artificial Nichoid on the morphology and mechanobiological response of mesenchymal stem cells cultured in vitro. Cells 2020, 9, 1873; doi:10.3390/cells9081873
Carelli S, Giallongo T, Rey F, Barzaghini B, Zandrini T, Pulcinelli A, Nardomarino R, Cerullo G, Osellame R, Cereda C, Zuccotti GV, Raimondi MT. Neural precursors cells expanded in a 3D micro-engineered niche present enhanced therapeutic efficacy in vivo. Nanotheranostics 2021; 5(1):8-26. doi:10.7150/ntno.50633
Perottoni S, Neto NGB, Di Nitto C, Dmitriev RI, Raimondi MT, Monaghan MG. Intracellular label-free detection of mesenchymal stem cell metabolism within a perivascular niche-on-a-chip. Lab on a Chip. Feb 2021. doi:10.1039/d0lc01034k
Raimondi MT, Barzaghini B, Bocconi A, Conci C, Martinelli C, Nardini A, Testa C, Carelli S, Cerullo G, Chirico G, Gottardi R, Osellame R, Remuzzi A, Laganà M, Jacchetti E, Micro structured tools for cell modeling in the fourth dimension, Proc. SPIE 11786, Optical Methods for Inspection, Characterization, and Imaging of Biomaterials V, 117861T (20 June 2021); doi: 10.1117/12.259332
Ene-Iordache B, Campiglio CE, Raimondi MT and Remuzzi A (2021) Characterization of the Microflow Through 3D Synthetic Niche Microenvironments Hosted in a Millifluidic Bioreactor. Front. Bioeng. Biotechnol. 9:799594. doi: 10.3389/fbioe.2021.799594