Tiss'You Regenerative Company

Cartilage regeneration: myth or reality?

Some animals can regenerate entire parts of their body with an inner ability that does not require external intervention. One example is the axolotl, a small salamander that lives in Xochimilco lake, in Mexico, which can regrow limbs, lungs, spinal cord and even parts of the brain if they are damaged, without scars. Also, the common lizards that we are used to finding in our gardens can regenerate their tail, without difficulties (ed. and without stem cells injections). Humans have lost this biological peculiarity during evolution as far as we are not even able to counteract accumulative damage, such as the ones that occur with joints use and injuries. As a result, cartilage is consumed, developing osteoarthritis.

So far, the most common belief is based on the idea that cartilage cannot regenerate and that the recycling of matrix elements, such as collagen, is almost impossible due to the structural complexity of the tissue and the absence of vessels that should carry nourishment and oxygen. However, at Duke University, this issue has been studied and the comparison we made at the beginning was appropriate to discover that even in our cartilage, the most stubborn tissue in terms of regeneration, there is an innate regrow ability – so far unappreciated – regulated by the same mechanisms that allow the salamanders not to worry when they lose a limb around.

The team of researchers analyzed the biological clock of articular collagen, discovering that they can date proteins as “old” or “young” according to their turn-over (ed. the metabolic exchange of substances or cells). If we take the lower limb as an example, this protein age follows a position-dependent gradient: in the hip, we find the “oldest” proteins and in the ankle the “youngest”, while in the knee there’s a good average. So, the hip itself is an older joint in comparison with the ankle and less subject to self-repair mechanisms; that’s a fact that correlates properly with statistics showing that hip osteoarthritis is more frequent than ankle osteoarthritis, and also, as a result of damage, the hip healing rate is slower compared to knee or ankle healing. This “articular age” is not only a consequence of the joints mechanics and the load to which they are subjected, but it also depends on the biological activity of some molecules called microRNA, able to regulate the collagenic turn-over in humans and the regrowth of the limb in salamanders. They are, in fact, the same group of molecules, following a precise distribution gradient, resulting in more activity in the distal part of the limb (in the extremities) and less active in the proximal part (in the center). Consequently, it will be easier for a salamander to regenerate a “paw” than the entire limb and it is easier for a man to heal his ankle than his hip.

The axolotl is an animal model well characterized for regeneration and discovering that joint tissue repair is regulated by the same elements, albeit limited, is a big step forward in the development of new therapeutic approaches. In modern medicine, many surgical techniques and different cell therapies are now used for cartilage reconstruction, but from a theoretical point of view, it is believed that cartilage cannot regenerate. This discovery comes after others that have demonstrated the presence of cell progenitors in mature cartilage and stem cells in neighboring tissues. Therefore, research should not only focus on slowing down the arthritic processes by extinguishing destructive catabolic phenomena, but also on providing anabolic elements to support – that’s something we can say today – the natural regenerative capacity of cartilage.

Omar Sabry

Sources:

Ming-Feng Hsueh, Patrik Önnerfjord, Michael P. Bolognesi, Mark E. Easley, Virginia B. Kraus. Analysis of “old” proteins unmasks dynamic gradient of cartilage turnover in human limbs. Science Advances, 2019; 5 (10): eaax3203 DOI: 10.1126/sciadv.aax3203

Alberto Siclari. Il trattamento delle lesioni cartilaginee. Cic, 2019. ISBN: 9788893890243

Tiss’You for cartilage repair

At Ciceron Hotel in Rome, the “International Cartilage Regeneration & Joint Preservation Society (ICRS)” will present its Focus Meeting entitled “One Step Cartilage Repair”. The society has always been a promoter of the themes around cartilage repair, through the divulgation of the latest news from the world of medical research. This year, ICRS offers a complete overview of all possible “one-step” interventions for cartilage defects, from bone marrow stimulation to the latest news regarding orthobiologics and regenerative medicine.

Tiss’You joined ICRS bringing a talk on the scientific agenda, through Prof. Riccardo Ferracini (Genoa) and Dr. Ilaria Roato (Turin), entitled: “Regenerative Treatment of Knee Osteoarthritis with Infusion of Low Manipulated Adipose Tissue”. This report will provide some preliminary data of the most recent studies in which the company is involved.
 

28th Isokinetic Medical Group Conference

During the 28th Isokinetic Medical Group Conference, we held a workshop entitled “Regenerative medicine and multimodal approach to prevent early osteoarthritis onset on late-career and former soccer players”. Our speakers Dr. Andrea Bruno¹, Dr. Massimo De Donato¹, and Dr. Elisabetta Tibalt² presented different approaches to manage the trauma and the degeneration of cartilage that can occur in professional and amateur athletes investigating how to ameliorate quality life – not only in sports people – but also in the larger population of former players.

Dr. Andrea Bruno spoke about regenerative medicine approaches, which can be a conservative and preventive approach to avoid major surgeries. Regenerative medicine tools are autologous cell and tissue therapies and involve PRP, bone marrow concentrates, adipose tissue derivatives (rich in mesenchymal stem cells), and mononuclear cells. The latter, due to its minimal invasiveness, was taken as an example showing the good clinical outcome in a case-report of a former marathoner suffering of grade II primary osteoarthritis (abstract and case report available in attachment).

Sometimes surgery is necessary, for example in a cartilage defect of traumatic origin. Dr. Massimo De Donato spoke about cartilage defects treatment, showing the rationale and good results of subchondral stimulation such as microfractures – which are iatrogenic fractures in the cartilage to promove its repair – but evidencing also the existing limits. For this reason, he introduced the argument of II-generation microfractures, namely nanofractures, which are more precise and standard, avoiding subchondral compaction and ameliorating cartilage repair with native type-II collagen and glycosaminoglycans (abstract available in attachment).

Treatment is only one step in the path of healing. Dr. Elisabetta Tibalt spoke about an underestimated but fundamental topic: the preliminary education and rehabilitation program that a patient must face before and after a regenerative treatment. Even if little can be found in the scientific literature, there are several good recommendations, i.e. quadriceps strengthening and neuromuscular joint control in case of knee osteoarthritis. The first phase of a biological activity must go along with protection and joint activation programs. After that, a second phase of progressive loading and functional joint restoration must follow. When there is cartilage repair maturation, it’s time for activity restoration.

¹Arthroscopic and Reconstructive Orthopedic Unit of the Knee, Head of unit: Dr. Enrico Arnaldi, Humanitas Research Hospital, Rozzano, Milan, Italy.

²ESW Therapy & Research Center, Rehabilitation Department, Head of unit: Dr. Stefano Respizzi, Humanitas Research Hospital, Rozzano, Milan, Italy

Tiss’You flies to London for the 28th Isokinetic Medical Group conference

During the last weeend of April, Wembley Stadium in London will host the 28th international Isokinetic conference dedicated to the prevention, diagnosis, treatment and rehabilitation of sports-related injuries. To fuel the collaboration between the famous sports medical group and our company [LINK = https: //www.tissyou.com/tissyou-care-isokinetic-shake-hands/], Tiss’You will be an important sponsor of the event.

During this conference, the football-related medical community aims to interface with global sports to encourage the knowledge share and best practices to improve the health, athletic development and performance of athletes. With the scientific collaboration of ortopeadic surgeons and specialists from Istituto Clinico Humanitas, we will contribute with a workshop dedicated to the prevention and treatment of early osteoarthritis in end-carrer and former athletes; the symposium program and the possibility of booking a place are available below:

Tiss’You in Cologne for IDS

The company exhibits its devices in the most important dental medicine meeting.

Tiss’You schedule is quite busy is March with international events: from 12th to 16th March, Tiss’You’s dental technology experts will be in Cologne for the IDS (International Dental Show), the biennial event for dental technology companies that records over 155,000 operators from 157 countries and 2305 companies from 59 countries.

IDS, a meeting occuring every two years, is a top-event for the wide range of exhibited products, welcoming dental professionals from all over the world.

Tiss’You, the first European Regenerative Company, while being in Germany for IDS exhibition, will also join the AAOS meeting in Las Vegas, the fair organized by the American Academy of Orthopedic Surgeons dedicated to orthopaedics.

IF YOU NEED US, WE ARE AT YOUR DISPOSAL.

VISIT US @ Stand A028 – Hall 5.2

HERE ARE OUR DIRECT CONTACTS:

FABRIZIO RAIMONDI
Business Development
f.raimondi@tissyou.com

MASSIMO NAPOL
Commercial Director
m.napol@tissyou.com

Tiss’You travel to Las Vegas

IF YOU NEED US, WE ARE AT YOUR DISPOSAL.
VISIT US @ booth number 6851

 

HERE ARE OUR DIRECT CONTACTS:

MAURO FIORINI
R&D manager
m.fiorini@tissyou.com

OMAR SABRY
Scientific marketing
manager
o.sabry@tissyou.com

MARCO MINIERO
CEO group
m.miniero@htamedica.com

MARIUS ENACHE
General manager
m.enache@htamedica.com

A successful Regenerative Battle offered by Tiss’You

A new way to do scientific communication from our company at the Ortho Center Meeting of Humanitas University

Tiss’You at Ortho Center Meeting in Humanitas University

Presenting the “Regenerative Battle”

Tiss’You will show its medical devices for regenerative medicine at ORTHO Center Meeting, organized by Humanitas University in Rozzano (MI) on 22nd and 23rd February and directed by Prof. Maurilio Marcacci.

The most prestigious Italian orthopedics will be present at the conference, together with their colleagues from European to work and discuss together in high-level topics.

“In times when free and independent information on scientific innovations is increasingly difficult – wrote Prof. Marcacci in the presentation of this event – we decided to organize a conference that starting from the experience of professionals can offer a frank critical comparison of opinions and strategies”.

Tiss’You organized, within the event, on Friday 22nd, an innovative comparison on the key issues of regenerative medicine. Four doctors will compete in a “REGENERATIVE BATTLE” on the biological issues presenting the opportunities offered for the regeneration of cartilage and tendon.

The speakers will be Dr. Elizaveta Kon from Humanitas Milan (bone marrow concentrate), Dr. Laura De Girolamo from Galeazzi Milan (adipose tissue), Dr. Francesca De Caro from Humanitas Gavazzeni Bergamo (monocytes) and Dr. Laura Mazzucco from Alessandria hospital (PRP).

The referee and moderator of the challenge will be the bio-expert lawyer Stefano Fiorentino.

At the end of the Regenerative Battle, guests can meet the experts from Tiss’You to obtain further information on the products and technologies that the company provides.

PRP: Platelet-Rich Panacea? No, but…

What is really PRP? Why does it work and why is it so often used? Is there any risk in using it?

In order to answer these questions, we interviewed Dr. Laura Mazzucco, a biologist in charge of the Laboratory of Transfusion Medicine at Ospedale SS. Antonio e Biagio e Cesare Arrigo in Alessandria and a leading expert in the field of blood components for non-transfusion use and regenerative medicine. Mazzucco has always been an enthusiast of platelets. She was one of the first researchers who started to use platelet lysate, that is “platelet juice”, in her experiments to stimulate cell growth.

PRP is a widely spread biological therapy boasting consolidated results in scientific literature. As suggested by the acronym, it is platelet-rich plasma obtained from autologous blood (when donor and recipient coincide – editor’s note) through platelet concentration. The underlying rationale is to give patients their own molecules in order to foster balance in tissues damaged by traumas, such as muscle-tendon injuries, or by degenerative processes such as arthrosis. How does PRP work?

“PRP can give some relief because damaged tissues are affected by fibrosis since they lack such molecules. The supply of a whole group of molecules to that areas – which lack innervation, circulation and microcirculation – sometimes sets ideal conditions for cell re-homing. Sometimes people tell me: “you may obtain the same results without using PRP”. Yes, it’s highly probable, but it would take longer. PRP acts in a few-months’ time. After one year, the results may be the same but PRP acts in the short term”.

Dr. Mazzucco highlights the importance of the role played by doctors in making their diagnosis, the most important moment in patients’ treatment pathway. “I think that the attitude towards PRP is very positive. However, this choice should be a possibility. There shouldn’t be just one therapy. We have created pathways. A few patients come after first screening but most patients have already tried conventional therapies before they approach PRP. People suffering from eye diseases are likely to have PRP as their first choice since these treatments have very good effects on such illnesses. Actually, therapies based on autologous serum have been used for fifty years”.

Some people are questioning PRP usefulness since it has been used in similar ways for different illnesses but in Mazzucco’s opinion, this isn’t a good reason to discredit it. “This product was designed to be used in difficult, improbable cases such as extremely serious ulcers or pre-amputation ulcers in diabetes. Then, we started to ask for miracles from it but this is not a miraculous product. This product should be used as an adjuvant in clinical pathways. The problem with PRP is that it was deemed a panacea, but it isn’t”. – “I strongly believe in the use of PRP in different sectors. Our tissues contain cells which proved to have higher response to PRP than others but this is indeed a good product suitable for all uses”.

Nowadays, on the market, there are many different types of technology and we should distinguish between them according to quality criteria set by a specific law (DM of 2 November 2015, Annex X). “The differences are those we have already mentioned. Firstly, the number of concentrated platelets. We focused on this point to standardise the product and classify it. This aspect is not related to biological effectiveness but it is a standard. The National Blood Centre had to set a point of reference to classify various types of PRP. When the number of platelets was defined, we could not imagine that such a number of products would be put on the market. At that time, we used different names for the same thing: platelet-rich plasma. From there, one thing was added and then another… it’s like in cooking, a pinch of salt, a pinch of basil (laugh)… from there came all these products, which are very similar in terms of clinical aim. There is not much evidence that platelet concentrate is better than PRF (platelet-rich fibrin) or than leuko-PRP (platelet- and leukocyte-rich plasma).”

As for the future of PRP, is it possible that, in the following years, this therapy will develop into a “second-generation” PRP? “I often think about this. Surely, the second generation of PRP will be industrially made although I fear that there is no will to do it.

I believe that the industrialisation of PRP may be linked to homologous blood collection in order to obtain the product starting from derivatives and transfusion remnants. It is also possible to lyophilise PRP. I have one sample dating back to 2003 so I strongly believe in this method.

The strongest point of PRP is the fact that no side effects have been observed up to now. Probably, this world of factors in plasma and platelets is balanced. Any modification to concentration and industrialisation will require deep investigation. I’m not saying you can’t do it, but it will be difficult to make it as globally widespread as it is today. We haven’t seen such an interesting market yet”.

Omar Sabry