Antonio Marmotti MD was born in Rome (Italy) in 1969 and studied medicine at the University of Turin (Italy), graduating in 1994. After completing his military service at the AVES (Italian Military Air Force) as medical officer and participating in NATO’s ‘Constant Force’ Peace Mission in Sarajevo (Bosnia) in 2000, he finished his Residence in Orthopaedics in Turin and started at the Department of Orthopaedics under the direction of Prof. Paolo Rossi (Mauriziano Hospital) where he is still practising. He is also currently involved in part-time research at the Molecular Biotechnology Center (MBC) at the University of Turin where he is investigating various aspects of one stage cartilage repair. In 2006, Antonio and his team were awarded the $15,000 ESSKA/DJO Biannual Research Grant for innovative scientific work in the field of Sport Traumatology and Rehabilitation. The purpose of this initiative is to encourage researchers to set up professional research projects to give more scientific basis to current and future treatment methods.
What first attracted you to dedicate part of your time to cartilage research?
My boss and mentor, Prof. Paolo Rossi, and my colleagues, Prof. Filippo Castoldi and Prof. Roberto Rossi, at the Department of Orthopaedics at Mauriziano Hospital (University of Turin) have always steered me towards biology in orthopaedics as an important field to develop for the future, which has led to a lot of travel throughout Italy and Europe, including Strasbourg and Gothenburg. I was then fortunate to find a great teacher and a constant inspiration in Prof. Mats Brittberg, the ‘father’ of cartilage research in Europe. Initially, I spent three weeks with him at the Cartilage Research Unit at Kungsbacka Hospital, (University of Gothenburg), where I followed both his clinical practice and laboratory research.
What persuaded you to apply for the ESSKA/DJO Grant in 2006?
It was encouragement from Prof. Roberto Rossi who sent me the application forms and, together with Prof. Filippo Castoldi, we designed the research methodology for “one stage osteochondral repair” with cartilage fragments in a PRP-hyaluronic acid scaffold.
Can you summarise the purpose of the study?
We hypothesised that cartilage fragments, without cell culture, could be a valuable source of cells for cartilage repair if ‘driven out’ of the cartilage matrix by a suitable scaffold that could give both mechanical and biochemical stimuli toward migration and maintenance of chondrocyte phenotype. We then conceived a scaffold made with hyaluronic acid (in the form of a membrane), platelet rich plasma (as a natural undifferentiated ‘reservoir’ of growth factors) and fibrin glue (as a mechanical structure enabling cells to flow out of the tight cartilage matrix). We designed an in vitro human and animal study and an in vivo animal model to verify our concepts.
Can you outline the significance of the results of your research?
Having completed all the animal studies, we found the in vivo model obtained good results, especially in the larger animal model. We identified a repair tissue that shares similar properties as hyaline cartilage, for example, the presence of collagen type 2 and its mechanical hardness and elasticity. It’s a different repair tissue that is obtained by more complex 2-stage systems (i.e. chondrocyte transplantation as ACI and MACI), but the main advantage of our process is that it only requires a single stage procedure without expensive cell culture. During our four years of research, we found a similar application of these concepts in the works of Prof. Giuseppe Peretti and in the cartilage repair system known as CAIS. Realising that we are not alone in thinking in this way is encouraging: perhaps we have found a valuable solution for the complex problem of intra-articular cartilage lesions!
Where has all this experience taken you and your team?
In 2006, we established a small group of cartilage researchers in Turin; in 2008 Dr Davide Edoardo Bonasia joined our ‘orthopaedic force’ sharing his valuable experience from Iowa University. Since 2009 biologist, Dr. Cristina Realmuto has worked at the MBC laboratory and is involved in all cell culture and explant culture analysis. We have also created an ongoing collaboration with some veterinary surgeons who will continue to work on the animal models, as well as with the Haematology Department run by Prof. Corrado Tarella who is giving us advice on our in vitro studies.
Where did you perform the studies?
We carried out all the in vitro studies at the MBC, thanks to indispensable support from Prof. Lorenzo Silengo who allowed our team to “colonise” a corner of his impressive laboratory. This location also presented a perfect environment in which to exchange ideas with the orthopaedic surgeons and biologists working full time in different fields of scientific research at the MBC, including Prof. Ferdinando Di Cunto and Prof. Guido Tarone.
For our in vivo studies we collaborated with two veterinary surgeons, Prof. Bruno Peirone and Prof. Mitzy Mauthe Von Degerfeld at the Department of Animal Pathology, Grugliasco, Turin.
Where have you presented your ‘interim’ results?
At two meetings in Italy: the IORS (Italian Orthopaedic Research Society) Meeting in 2010, the SIGASCOT 2010 meeting (the ‘Best Paper’ session); and at three international meetings: AOSSM 2010, ESSKA 2010 (where we won the “Best Poster” award for the ‘Cartilage’ session (KSSTA Vol 18, suppl 1, June 2010 poster n° P16-1206) and ICRS 2010. The abstracts and presentations can be found at the societies’ websites.
Do you think that the DJO Grant is a useful initiative to encourage young people to start research projects?
Certainly yes! I really think every young science or clinical researcher who has identified a project that requires funding should apply for the DJO Grant. As well as the invaluable financial support, it also gives the winners self-belief and added motivation and brings credibility to the project. Reflecting on the last four years, my colleagues and I recognise that the DJO Grant gave us the opportunity to fulfil our research ambition and we clearly remember with pride and genuine happiness the moment we received it.
What are the next steps?
We have now finished the pre-clinical studies, with the help of a grant from an Italian bank (CRT-Cassa di Risparmio di Turin). We are still continuing with our in vitro research into the migration of chondrocyte from cartilage fragments under different growth factor exposures, and trying to optimize in vitro the migration-proliferation of condrocytes in our scaffold in order to obtain better and quicker repair in vivo. Our next logical step is to conduct an in vivo Phase 1 human clinical study and we are waiting to hear if our application to the ethical committee has been accepted.
What are your future plans in cartilage research?
We want to establish a reference centre for cartilage research and treatment at the Mauriziano University Hospital. From the clinician’s point of view, we want to offer specialist cartilage repair consultations for the knee, ankle, shoulder and hip to create a reference for patients for simple and complex clinical problems. On the research side, we are continuing to develop projects on osteochondral repair. We are also planning to start using bone marrow components, as well as cartilage fragments, to promote repair without major cell manipulation, which means we can still offer one-stage repair procedures.