News

The value of collagen and the innovation of peptides

Carried out by Ferdinand Magellan in 1520, the first circumnavigation of the globe ended with the dramatic loss of almost the entire crew due to scurvy. This disease presents catastrophic symptoms such as small and numerous bleedings caused by the fragility of blood vessels, failure to heal wounds, teeth loss, widespread pain, respiratory failure, and cardiac arrest. The cause was found in the food: vitamin C was not present at all in the supplied carried onboard. This micronutrient, found in citrus fruit, fresh fruit, pepper, tomatoes, potatoes, and broccoli, can only be assimilated through the diet. It is essential for the amino acid proline’s hydroxylation, which is a fundamental process for the synthesis of collagen. Without this reaction the degeneration of collagen triggers scurvy, a disease that did not only affect pirates and explorers in the past but also represents a risk for some populations today.

 

Collagen is the main protein of all connective tissues. It is an elastic protein with a supporting function, formed by three polypeptide chains wrapped together. This particular structure can create more excellent resistance to tension than a steel wire of equal diameter. The chains are made of a repeated tri-peptide unit, glycine-X-Y, where generally X is a proline (Pro) and Y a hydroxyproline (4-Hyp). Glycine is needed to tighten the collagen chains, while Pro and 4-Hyp are responsible for the chains’ coiling (the importance of vitamin C hides here). Although evolution has developed such sophisticated resistance, collagen is not free from specific degradation processes, such as trauma, oxidative stress, and inflammation. The release of peptides from the collagen chain triggers new collagen synthesis and reshapes the extracellular matrix of connective tissues. Exploiting this mechanism, even the exogenous administration of peptides provides the essential elements for the protein’s reconstitution, activating the biosynthesis processes and negatively regulating the degradation processes. Food supplementation of collagen peptides follows just this philosophy. Still, the effects are minor and require high amounts of peptides for prolonged periods due to their dispersion in all tissues and not only in the target areas.

 

Recently, we announced the arrival of the Arthrys, a medical device based on a ready-to-use injectable solution of hydrolyzed collagen peptides, further enriched with vitamin C and magnesium to protect peptides from oxidation. Tiss’You has developed Arthrys as a comfortable injection to immediately drive these peptides where needed. This device can be used in any medical practice to treat small and large joints, tendons, muscles, and ligaments. The high concentration of peptides allows strengthening tissues’ collagen structure, stimulating their synthesis and preventing their degradation through a pro-regenerative activity. Besides, treatment with peptides counteracts pain and inflammation and improves joint function.

Arthrys is an easy infiltration that lasts a few seconds and can be performed by your physician. It can be used alone or in combination with other treatments. It is also indicated to improve the surgical course following surgery, reducing post-operative pain, and accelerating functional recovery.

CE mark approval for Arthrys

Tiss’You has obtained CE mark approval for Arthrys, a new medical device based on peptides derived from hydrolyzed collagen.

Within the mission to always look for new and better solutions to help our body’s natural healing abilities, Tiss’You has developed Arthrys, a ready-to-use injectable solution for the intra-articular treatment of osteoarthritis and for structural strengthening of connective tissues. Its mechanism of function is based on peptides with an average molecular weight of 3KDa. The formulation of this device, enriched with vitamin C and magnesium, directly strengthens the structure of the extra-cellular tissue matrix naturally rich in collagen, decreasing pain and improving joint function.

 

Read the product sheet for more information.

Monocytes treatment for hip OA – Case Report

The orthopaedic group led by Dr. Vincenzo Madonna at Humanitas Castelli in Bergamo has published a case report using our device Monocytes.

Regenerative medicine is useful for treating damaged tissues through a minimally invasive approach. In this way, it is possible to prevent major surgeries, or speed up recovery after surgery. When we talk about last-stage osteoarthritis, however, it is necessary to sacrifice the joint with a prosthesis and biological therapies are no longer useful. Nevertheless, cartilage often ages on both joint sides and when it’s time for the implantation of a prosthesis (ed. knee or hip, it is the same), regenerative medicine can be useful in the so-called “contralateral” joint, ie in the opposite side.

In this work, the clinical results of this therapeutic strategy emerge. Before treatment, the patient reported disability and lameness caused by the arthritic condition of her right hip, which was a candidate for prosthesis, but also continuous pain and limitation of mobility on the left side. The replaced hip (the right one) achieved the expected good results, but also the other joint treated (the left one) with Monocytes (ed. mononuclear cells from peripheral blood) showed total pain relief and excellent recovery of mobility, with a very high index of satisfaction from the patient.

Monocytes can restore joint homeostasis through the release of growth factors and inflammation mediators. Moreover, macrophages, which derive from the differentiation of monocytes, can recycle the oxidized elements of synovial fluid such as hyaluronic acid and lubricin, improving the metabolic and mechanical balance of the joint.

We thank all the authors of the work and in particular Dr. Francesca De Caro for the care and sharing of the work, which is available for a consultation below.

 

Francesca De Caro, Arcangelo Russo, Gabriele Cortina, Marco Collarile, Vincenzo Condello, Vincenzo Madonna. New Trends in Treatment of Osteoarthritis: “From Cells to Metal”. A Case Report of Simultaneous Different Approach to Bilateral Hip Osteoarthritis. Ann Case Report 2019, 11: 247. DOI: 10.29011/2574-7754/100247

 

Omar Sabry

 

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

The first European Regenerative Company exhibits to AAOS

After joining the two most important medical exhivition in the Middle East (AAEDC and Aarab Health in Dubai), it’s time for Tiss’You – the first Regenerative Company of Europe – to travel straight to the United States of America. From March 12th to 15th, managers and sales representatives from San Marino will partecipate to AAOS exhibition, the American Academy of Orthopedic Surgeons, in Las Vegas.

 

The goal is to grow contacts overseas with distributors and medical facilities to promote and commercialize medical devices designed and manufactured by Tiss’You that, with the headquarters in the United States in the upcoming months, will benefit the FDA certification (the equivalent of the CE mark for the USA).
The fair organized by AAOS is one of the most prestigious in the United States and certainly the best known overseas in the orthopedic field.

 

At the same time, Tiss’You’s dental technology professionals will be in Cologne for the IDS (International Dental Show), a biennial event, specific for dental technology companies – with over 155,000 operators from 157 countries and 2305 companies from 59 countries.

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 showed its medical devices for regenerative medicine last weekend at the Ortho Center Meeting, organized by Humanitas University in Rozzano (MI) under the direction of Prof. Maurilio Marcacci.
The most famous Italian orthopedic surgeons partecipated in the prestigious conference with prestigious European doctors, discussing high-level topics in their field.
Tiss’You has organized on Friday 22nd, within the event, an innovative comparison on the key issues of regenerative medicine, a branch in which the company is highly specialized. Dr. Elizaveta Kon from Humanitas (Milan), Dr. Laura De Girolamo from Galeazzi (Milan), Dr. Francesca De Caro from Humanitas Gavazzeni (Bergamo), and Dr. Laura Mazzucco from the Hospital of Alessandria challenged each other in the first edition of the Regenerative Battle comparing the different opportunities to issue the topic of tissue regeneration: bone marrow concentrate, adipose tissue derivatives, peripheral blood mononuclear cells, and PRP. The lawyer Stefano Fiorentino was the moderator of the “battle”.
At the end of the event the participants obtained further information from Tiss’You experts, who were highly satisfactied for the success of this event.