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RESEARCH AREA AND TRANSLATIONAL RESEARCH

The Regenerative Medicine Technologies Lab adopts an interdisciplinary approach, at the intersection of engineering, biology and medicine, aiming at regenerating biological tissue substitutes in vitro. Major RMT lab competences are represented by advanced technologies such as biofabrication and microfluidics, enabling tools for the generation of innovative constructs replicating the complexity of in vivo biology. In more detail, in RMT Lab we generate 3D tissues based on cell co-cultures mainly of human origin, embedded in suitable biomaterials and cultured in engineered environments providing biophysical and mechanical stimuli. RMT Lab mainly focuses on musculoskeletal tissues, producing biological replicates with a scale ranging from microfluidic devices to macro-scale constructs of clinically relevant dimensions. The microarchitecture of physiological tissues can be hierarchically replicated, spanning from mimicking the interface between different tissues (e.g. tissues composing the joints or the tendon bony insertion) down to the reproduction of microscale tissue features (e.g. bone trabeculae or microvascular networks).

From a translational point of view, smaller scale devices are currently being improved towards high throughput platforms usable for drug screening purposes and testing of personalized therapies, whilst bigger scale constructs could be translated to biological substitutes usable in clinics for the regeneration of diseased tissues. In particular, we are working on reproducing bone, cartilage and skeletal muscle constructs, to improve drug discovery and to personalize available therapies in fields such as bone tumors, osteoarthritis and muscle fibrosis. In the field of bone tumors, we demonstrated that our models were able to reproduce the effects of known anti-tumor drugs on cancer cells better than simple 3D cancer cell models. We are also working on improving the mechanical properties of the support matrix through bioprinting techniques, and on increasing the throughput of our system to enable drug screening with a higher throughput.

About skeletal muscle, we are studying models able to replicate the main features of fibrotic muscle tissue, to provide advanced tools to researchers searching for new therapies. The currently generated models have shown that they can replicate the organization of muscle fibers, the presence of a vascular network similar to that present in vivo, and better reproduce the altered production of extracellular proteins in pathological conditions as compared to the corresponding 2D models.

In the RMT Lab we also develop patient-specific multi-tissue 3D models, such as a microfluidic model of an osteoarthritic joint, that allow to compare different possible therapeutic approaches for the single patient and can represent an innovative instrument for the development of personalized therapeutic regimens for osteoarthritis and other orthopedic pathologies.

RESEARCH METHODS

In the RMT Lab, innovative diagnostic and therapeutic methodologies are designed and developed, with particular reference to miniaturized 3D models in vitro that reproduce different tissues, mainly musculoskeletal, including bones, cartilage and muscles, vascularized when necessary. The creation of miniaturized 3D models is based on the use of innovative technologies such as bio-manufacturing (including 3D printing and bio-printing) and microfluidics. A fundamental element of the 3D models is represented by cells, mostly of human origin, obtained commercially or directly isolated from surgical waste fragments. To obtain the formation of 3D tissues, different cell populations of the reproduced tissue are co-cultured and incorporated into hydrogels injected into microfluidic or macroscale culture devices, which are custom developed in the laboratory. The models developed can be used for the study of physio-pathological mechanisms or for the evaluation of drugs and therapies, by means of analyses mainly based on confocal and fluorescent imaging, as well as secretome analysis assays. Furthermore, we perform quantitative analyses on the cells extracted from the models themselves, such as PCR and flow cytometry.

GROUP LEADER
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Matteo Moretti Prof. Eng.

BRIEF CV

Prof. Matteo Moretti is the head of the Regenerative Medicine Technologies Laboratory at the Ente Ospedaliero Cantonale (EOC), Adjunct Professor at the Biomedical Sciences Faculty of Università della Svizzera Italiana (USI) Lugano, Switzerland and head of the Cellular and Tissue Engineering Laboratory at the IRCCS Galeazzi Orthopedic Institute, Milan, Italy. He previously worked as a post-doc researcher in the Langer Lab at the Massachusetts Institute of Technology, Harvard-MIT Division of Health Science and Technology. Both of his titles, B.Eng (Polytechnic of Milan) and M.Sc (Trinity College Dublin, Ireland) are in Bioengineering. He obtained a European doctorate in 2005 in Bioengineering at Polytechnic of Milan, sharing his research period with the Tissue Engineering Laboratory of Prof. I.Martin at University of Basel.

His main research interests are advanced cell culture technologies for musculoskeletal tissues and their pathologies. In particular, he focuses on biofabrication of engineered tissues and in vitro models, 3D tumor and fibrosis pathological models and tissue microvasculature; merging them with multi-scale bioreactor systems as key tools for effective and accessible traditional and biological therapies towards personalized medicine and high-content screening systems. His scientific awards include a N.A.S.A. Tech Brief Award, for the development of scientific or technical innovations. Industrially, he has been coordinator of European projects for Fidia Advanced Biopolymers, has a licensed patent and has been co-founder of 2 biotech start-ups (SKE S.R.L. and Cellec A.G.) focused on bioreactor technologies. He is the author of more than 95 articles in international peer-reviewed scientific journals.

RESEARCHERS
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Chiara Arrigoni

RESEARCH ASSOCIATE

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Simone Bersini

RESEARCH ASSOCIATE

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Maria Vittoria Colombo

PHD STUDENT

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Daniele D’Arrigo

PHD STUDENT

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Riccardo Francescato

PHD STUDENT

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Anaïs Lamouline

PHD STUDENT

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Laura Longo

MASTER STUDENT

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Michela Magnoni

MASTER STUDENT

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Valerio Mainardi

POSTDOC

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Dalila Petta

POSTDOC

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Luca Possenti

VISITING POSTDOC

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Alice Salvadori

MASTER STUDENT

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Giuseppe Talò

RESEARCH ASSISTANT

RECENT PUBLICATIONS
  • Chen S, Wang H, Mainardi VL, Talò G, McCarthy A, John JV, Teusink MJ, Hong L, Xie J. Biomaterials with structural hierarchy and controlled 3D nanotopography guide endogenous bone regeneration. Sci Adv. 2021 Jul 28;7(31):eabg3089.
  • Gilardi M, Bersini S, Valtorta S, Proietto M, Crippa M, Boussommier-Calleja A, Labelle M, Moresco RM, Vanoni M, Kamm RD, Moretti M. The driving role of the Cdk5/Tln1/FAKS732 axis in cancer cell extravasation dissected by human vascularized microfluidic models. Biomaterials. 2021 Jul 20;276:120975
  • Mondadori C, Palombella S, Salehi S, Talò G, Visone R, Rasponi M, Redaelli A, Sansone V, Moretti M, Lopa S. Recapitulating monocyte extravasation to the synovium in an organotypic microfluidic model of the articular joint. Biofabrication. 2021 Jun 17
  • Cruz-Moreira D, Visone R, Vasques-Nóvoa F, S Barros A, Leite-Moreira A, Redaelli A, Moretti M, Rasponi M. Assessing the influence of perfusion on cardiac microtissue maturation: A heart-on-chip platform embedding peristaltic pump capabilities. Biotechnol Bioeng. 2021 Aug;118(8):3128-3137.
  • Alvarado-Estrada K, Marenco-Hillembrand L, Maharjan S, Mainardi VL, Zhang YS, Zarco N, Schiapparelli P, Guerrero-Cazares H, Sarabia-Estrada R, Quinones-Hinojosa A, Chaichana KL. Circulatory shear stress induces molecular changes and side population enrichment in primary tumor-derived lung cancer cells with higher metastatic potential. Sci Rep. 2021 Feb 2;11(1):2800.
  • Huang D, Liu T, Liao J, Maharjan S, Xie X, Pérez M, Anaya I, Wang S, Tirado Mayer A, Kang Z, Kong W, Mainardi VL, Garciamendez-Mijares CE, García Martínez G, Moretti M, Zhang W, Gu Z, Ghaemmaghami AM, Zhang YS. Reversed-engineered human alveolar lung-on-a-chip model. Proc Natl Acad Sci U S A. 2021 May 11;118(19):e2016146118.
  • Possenti L, Mecchi L, Rossoni A, Sangalli V, Bersini S, Cicchetti A, Costantino ML, Candrian C, Arrigoni C, Rancati T, Moretti M. Radiobiological Studies of Microvascular Damage through In Vitro Models: A Methodological Perspective. Cancers (Basel). 2021 Mar 9;13(5):1182
  • Colombo MV, Bersini S, Arrigoni C, Gilardi M, Sansoni V, Ragni E, Candiani G, Lombardi G, Moretti M. Engineering the early bone metastatic niche through human vascularized immuno bone minitissues. Biofabrication. 2021 Apr 26;13(3).
  • El Soury M, García-García ÓD, Moretti M, Perroteau I, Raimondo S, Lovati AB, Carriel V. Comparison of Decellularization Protocols to Generate Peripheral Nerve Grafts: A Study on Rat Sciatic Nerves. Int J Mol Sci. 2021 Feb 27;22(5):2389.
  • Mainardi VL, Arrigoni C, Bianchi E, Talò G, Delcogliano M, Candrian C, Dubini G, Levi M, Moretti M. Improving cell seeding efficiency through modification of fiber geometry in 3D printed scaffolds. Biofabrication. 2021 Feb 12
  • Crippa M, Bersini S, Gilardi M, Arrigoni C, Gamba S, Falanga A, Candrian C, Dubini G, Vanoni M, Moretti M. A microphysiological early metastatic niche on a chip reveals how heterotypic cell interactions and inhibition of integrin subunit β3 impact breast cancer cell extravasation. Lab Chip. 2021 Mar 21;21(6):1061-1072
  • Visone R, Ugolini GS, Cruz-Moreira D, Marzorati S, Piazza S, Pesenti E, Redaelli A, Moretti M, Occhetta P, Rasponi M. Micro-electrode channel guide (µECG) technology: an online method for continuous electrical recording in a human beating heart-on-chip. Biofabrication. 2021 Feb 9
  • Zoia L, Morelli A, Talamini L, Violatto MB, Lovati AB, Lopa S, Recordati C, Toffanin C, Salanti A, Russo L, Colombo L, Moretti M, Salmona M, Ferla B, Bigini P. Cellulose nanocrystals: a multimodal tool to enhance the targeted drug delivery against bone disorders. Nanomedicine (Lond). 2020 Aug;15(23):2271-2285.
  • Petta D, Basoli V, Pellicciotta D, Tognato R, Barcik JP, Arrigoni C, Della Bella E, Armiento AR, Candrian C, Richards GR, Alini M, Moretti M, Eglin D, Serra T. Sound-induced morphogenesis of multicellular systems for rapid orchestration of vascular networks. Biofabrication. 2020 Sep 25
  • Lovati AB, Lopa S, Bottagisio M, Talò G, Canciani E, Dellavia C, Alessandrino A, Biagiotti M, Freddi G, Segatti F, Moretti M. Peptide-Enriched Silk Fibroin Sponge and Trabecular Titanium Composites to Enhance Bone Ingrowth of Prosthetic Implants in an Ovine Model of Bone Gaps. Front Bioeng Biotechnol. 2020 Oct 19;8:563203
  • Mondadori C, Crippa M, Moretti M, Candrian C, Lopa S, Arrigoni C*. Advanced Microfluidic Models of Cancer and Immune Cell Extravasation: A Systematic Review of the Literature. Front Bioeng Biotechnol. 2020 Aug 26;8:907.
  • Marchetto A, Ohmura S, Orth MF, Knott MML, Colombo MV, Arrigoni C, Bardinet V, Saucier D, Wehweck FS, Li J, Stein S, Gerke JS, Baldauf MC, Musa J, Dallmayer M, Romero-Pérez L, Hölting TLB, Amatruda JF, Cossarizza A, Henssen AG, Kirchner T, Moretti M, Cidre-Aranaz F, Sannino G, Grünewald TGP. Oncogenic hijacking of a developmental transcription factor evokes vulnerability toward oxidative stress in Ewing sarcoma. Nat Commun. 2020;11(1):2423
  • Ragni E, Palombella S, Lopa S, Talò G, Perucca Orfei C, De Luca P, Moretti M, de Girolamo L. Innovative Visualization and Quantification of Extracellular Vesicles Interaction with and Incorporation in Target Cells in 3D Microenvironments. Cells. 2020;9(5):1180.
  • Lopa S, Piraino F, Talò G, Mainardi VL, Bersini S, Pierro M, Zagra L, Rasponi M, Moretti M. Microfluidic Biofabrication of 3D Multicellular Spheroids by Modulation of Non-geometrical Parameters. Front Bioeng Biotechnol. 2020;8:366.
  • Arrigoni C, D’Arrigo D, Rossella V, Candrian C, Albertini V, Moretti M. Umbilical Cord MSCs and Their Secretome in the Therapy of Arthritic Diseases: A Research and Industrial Perspective. Cells. 2020;9(6):E1343. Published 2020 May 28
  • Perucca Orfei C, Lovati AB, Lugano G, Viganò M, Bottagisio M, D’Arrigo D, Sansone V, Setti S, de Girolamo L. Pulsed electromagnetic fields improve the healing process of Achilles tendinopathy: a pilot study in a rat model. Bone Joint Res. 2020 Oct 5;9(9):613-622
  • Arrigoni C, Lopa S, Candrian C, Moretti M. Organs-on-a-chip as model systems for multifactorial musculoskeletal diseases. Curr Opin Biotech 2020 Jun;63:79-88.
FUNDINGS
  • SNSF
  • EU – ITN Marie Curie
  • AIRC Investigator Grant
  • Fondation Suisse de Recherche sur les Maladies Musculaires (FSRMM)
PHOTOGALLERY