News

Clinical report of Arthrys double treatment on 20 patients

We are releasing a preliminary report of our Arthrys post-market clinical follow-up (PMCF) done in collaboration with Dr. Francesco Fiacchi, orthopaedic surgeon in Mantua (Suzzarra).

This PMCF activity enrolled patients with knee and hip osteoarthritis, treated with a first intra-articular injection of Arthrys 5mg/ml and a secondary shot of the same product at six months. We have assessed the safety and effectiveness of hydrolyzed collagen in ameliorating pain and functionality symptoms and its feasibility for re-treatment.

The report is available for direct download here or on Arthrys portfolio page.

 

New clinical report on Guided Bone Regeneration (SpherHA and Collygen)

In collaboration with Dental School in Turin, we are releasing a preliminary clinical report on the efficacy and safety of a guided bone regeneration strategy for the treatment of post-extraction sockets.

This post-market clinical follow-up shows successful bone and soft tissue regeneration after the use of SpherHA hydroxyapatite and Collygen protective membrane. The report is available here for direct download, or on SpherHA and Collygen portfolio pages.

New Arthrys clinical report

We are releasing a preliminary report of our Arthrys post-market clinical follow-up (PMCF). We are grateful to Dr. Federico Valli, orthopaedic surgeon in Milan, for his collaboration.

This PMCF activity was performed on osteoarthritis patients treated with one shot of Arthrys 5mg/ml, showing its safety and effectiveness in ameliorating pain and functionality symptoms.

The report is available for direct download here or on Arthrys portfolio page.

Medica 2021, World Forum for Medicine

Tiss’You will be present in Düsseldorf (Germany) for Medica 2021, World Forum for Medicine, from 15 to 18 October.

After an online edition due to the Covid-19 pandemic, the most important international trade fair for medicine is back with 2900 exhibitors from over 70 countries, with a rich program of presentations and conferences. There will be wide coverage on the most innovative healthcare topics: robotics and automation, the entry of artificial intelligence into medical routines and patient wearable devices, virtual reality in surgery, and the progressive digitalization of the medical world.

Tiss’You will welcome you at booth D48 in Hall 10 to present its products and biomaterials for regenerative medicine. In recent years, regenerative medicine has become a trend as a minimally-invasive approach to treat degenerative diseases. Some examples are osteoarthritis and musculoskeletal disorders for which we developed Arthrys, a medical device based on an injectable solution of hydrolyzed collagen peptides, which is indicated for the direct reinforcement of the extracellular matrix of connective tissues, naturally rich in collagen fibers. The innovative formulation of Arthrys can be exploited as a minimally invasive treatment for aging, degeneration, trauma, overload, and postural defects that cause pain and limited mobility in musculoskeletal structures, such as joints and surrounding connective structures (i.e., muscles, tendons, ligaments, menisci).

SpherHA – Antibiotic release test

Reconstructive bone surgery aims to regenerate the loss or resorption of bone through materials and techniques that allow to mimic and activate specific and fundamental reparative mechanisms such as osteogenesis, osteoinduction, and osteoconduction.

With general good health conditions, the bone displays an excellent healing capacity; therefore, in case of bone defects, it is sufficient to fill the void of the loss of substance with grafts or bone substitutes to provide the three-dimensional structure to sustain the regeneration process.

However, infection, e.g., osteomyelitis, is one of the major postoperative complications and evolves in complete bone disruption. Local delivery of antibiotics maximizes target tissue concentration and minimizes systemic toxicity risks. The use of bone substitutes exploited as antibiotic carriers is ideal to plan efficient and tailored bone regeneration strategies.

To help surgeons in this task, we tested SpherHA release capacity with the most common antibiotics; the results are available in the report below:

 

SpherHA –  Antibiotic Release Test Report – DOWNLOAD

3D PRINTING OF MEDICAL DEVICES AND ARTIFICIAL ORGANS: HYPE OR HOPE?

3D printing is a technology for the additive manufacturing of objects, i.e., adding material layer by layer starting from digital three-dimensional models. It promises to revolutionize many areas, including the medical field, because of the high flexibility for the production of medical devices and artificial organs. However, the high expectations of 3D printing collide with several limitations that need to be overcome, making 3D printing a declared yet unproven success.

3D printing already has applications in dentistry. A well-equipped dental lab can make custom crowns, bridges, and other prosthetic restorations for patients in a time-saving manner. Additive manufacturing can also be useful for reconstructing body parts following an accident: in 2013, the U.S. Food and Drugs Administration approved the use of a patient-specific cranial device from Oxford Performance Materials, Inc. that was designed based on computed tomography. The procedure allowed the reconstruction of 75% of the patient’s skull, and the company received subsequent approvals for 3-D printed facial reconstruction devices. 3D modeling is also useful for surgery planning, e.g., the prototype bone structures created by the Italian research group led by Nicola Bizzotto, or for forensic analysis for reconstructions of victims’ skulls and faces. In 2010, the use of 3D printing was proposed to predict, for educational purposes, the appearance of an unborn baby to simulate the presence or absence of deformities. The future will exploit 3D printing for tissue and organ printing, but in most cases, these are technologies and devices in the preclinical stage.

Artificial organ printing must overcome some limitations before becoming the new frontier of medical devices. First, the supporting scaffold must possess sufficient mechanical strength to be implanted in the body, be successfully vascularized, and have the necessary spatial resolution and internal structure to function as a tissue. Obstacles also exist from a regulatory standpoint: in both America and Europe, medical device regulation has strict rules to ensure the safety and performance of medical products. All of this collides with the biggest advantage of 3D printing: flexibility. Devices made by 3D printing can be highly customized, but this fits poorly with a system where it is generally impossible to change the basic design of a certified product. New rules are needed to ensure the reproducibility, sterility, and, last but not least, safety and performance of medical devices derived from 3D printing. In the future, authorization for the use of an artificial organ (or a medical device 3D-printed in an operating theatre) may be put upon an ethics committee rather than national regulatory bodies. In this case, however, it will be important to distinguish between research and medical treatment. Designing a custom device for a patient with a serious condition and stepping outside the boundaries of the state of the art may be considered medical practice rather than experimentation. However, even if the use of 3D printed dental prostheses would uprise fewer regulatory implications, more aggressive 3D printing-based procedures would subject patients to procedures under uncontrolled circumstances with uncertain outcomes. Finally, new unpredictable ethical dilemmas may arise: for instance, what if modeling healthy unborn fetuses’ prediction was leveraged to persuade a mother against abortion?

The Nobel Prize winner for literature Kazuo Ishiguro hypothesized in his famous novel Never Let Me Go a way for mankind to meet the need for organs for donation: the use of biological clones, created for exclusive and selfish use to ensure the life of human beings “born from parents”. The story is precise in observing two phenomena; the first is the need to find a solution to the transplant lists: every year, in the United States alone, there are more than one hundred thousand patients on the waiting list to receive an organ and, every day, there are about twenty deaths due to the lack of a donor. Overpopulation and the habits of the Western world steadily increase these numbers. The other phenomenon is the fundamental individualism that leads men to worry only about their own well-being, diverting science with positivistic drives and no ethical brakes.

Indeed, science fiction is a distortion and fails to predict the future, but it lucidly analyzes the present. Artificial organ printing may become the new frontier in the medical use of additive printing in the future, but we are still far from those days. In 2011, surgeon Anthony Atala of Wake Forest University described a preliminary study of organ regeneration in a TED talk, showing a bio-ink printed matrix in the shape of a kidney. Some journalists reported the scientifically incorrect news of the first artificial kidney that could be implanted and function. The enthusiasm and inaccuracy of the media, over the years, have generated inordinate hype towards the technology of 3D printing, which today finds itself in a peak of inflated expectations that cannot be realistically satisfied and risk disappointing – consequently invalidating the research and development of a promising technology.

Today, the consolation is that the use of scaffolds for regenerative medicine and tissue engineering exploits successful technologies, such as subtractive manufacturing: a bit the opposite of 3D printing, that exploit subtraction from blocks of raw material to obtain matrices, for example with the decellularization of animal tissues. At Tiss’You, this process is carried out with EstRem, a trans-esterification reaction capable of providing heterologous bone matrices that are perfectly compatible with humans.

Arthrys and the treatment of pain

Pain is a multifactorial pathology with social, psychological, and emotional components. In medicine, it is commonly considered as the consequence of a pathology or a trauma, but recently pain is acquiring relevance on its right and no longer only as a symptom. For instance, the pain that sometimes affects muscles, tendons, and joints depends on many factors, such as trauma, injuries, postural defects, and overload conditions. However, if appropriate, a doctor can specifically diagnose low back pain or knee pain. It is possible to diagnose osteoarthritis by observing articular cartilage degeneration on an x-ray, or tendon rupture on ultrasounds/MRI, but there is no absolute correlation between clinical signs and pain.

Pain leads patients to lose functions in daily, work, and sports activities, resulting in a challenge to clinicians. Except for orthopedic issues requiring surgery, musculoskeletal pain is often addressed with oral drugs or local cortisone infiltration, which are only temporary relief. However, to offer better benefits, pain therapy can take advantage of molecules and formulations with targeted action.

For joint pathologies, such as arthrosis, the use of hyaluronic acid (of different molecular weights) can provide relief to patients with joint pain through viscosupplementation, which improves the viscosity and elasticity of the synovial fluid.  Alternatively, regenerative medicine allows the use of the patient’s cells and elements to trigger the self-healing processes of injured tissues. One example is the use of Platelet-Rich Plasma (commonly known PRP, its acronym, or growth factors) that is obtained from blood withdraw from the patient himself and used immediately, after appropriate centrifugation.

Arthrys low molecular weight collagen peptides have a specific reinforcing action for connective tissue structures. Once injected into the site of interest, their concentration gradient can counteract the degradation phenomena affecting the extracellular matrix. Moreover, their weight of about 3kDa allows them to interact in the processes of inflammation and pain. The presence of Vitamin C and Magnesium protects the peptides from oxidation and allows a further antalgic action and the improvement of the cellular adhesion of the progenitor cells involved in the reparative processes.

Arthrys is a ready and easy-to-use solution that can quickly and naturally counteract pain and other symptoms of limited functionality.

The subjectivity of pain can have consequences on the response to therapy: awareness of the diagnosis and expectations of recovery are psychological features that may influence the clinical outcome. To find a solution to the high variability in response to treatments, research and development of new products are working to provide new and more effective solutions to combat pain.

New Lipocell publication for the treatment of osteoarthritis

There is a new article that demonstrates the safety and efficacy of Lipocell in the treatment of osteoarthritis. The research work, carried out by Dr. Marco Caforio and Prof. Carmelo Nobile, was published in the Journal of Clinical Medicine (I.F. 3.3) within the Special Issue “Recent Advances in Osteoarthritis Management and Regenerative Strategies”.

The study, approved by the ethics committee of the University of Calabria, recruited thirty patients who showed improvements in their symptoms of pain and loss of joint function after infiltration of purified autologous adipose tissue obtained with Lipocell, in association with arthroscopic lavage and debridement.

 

 

Lipocell now has three peer-reviewed papers demonstrating its efficacy in osteoarthritis treatment (see Castellarin et al., Bistolfi et al.).

 

Dr. Marco Caforio’s paper is available here.

What are the key changes in the new Medical Devices Regulation?

On May 26, 2021, the new Medical Devices Regulation, commonly abbreviated as MDR, will enter into force in Europe. It replaces the previous MDD (Medical Device Directive), which has been in the field since 1993 with the aim of harmonizing medical device laws in Europe. The MDR brings a significant amount of regulatory changes, with a major impact not only on manufacturers, but also on all stakeholders involved in the device lifecycle.

 

The new regulation is about four times more extensive than the previous one, in terms of documents and annexes, and the word “safety” appears 290 times compared to 40 in the MDD. All accidents, injuries, and eventual deaths related to the use of a specific device will be entered in a European portal with the task of centralizing and making transparent the information on medical devices. The new rules will require manufacturers to generate clinical data about the safety and performance of their devices, especially in relation to equivalence standards. Individual product traceability will be one of the critical aspects through the implementation of Unique Device Identification (UDI), required on all product labels.

The definition of “medical device” will also be expanded to include all devices previously defined as non-medical or aesthetic that were previously unregulated, e.g., products for disinfection, contact lenses, lasers for hair removal. Non-CE marked products will have to comply immediately with the general safety and performance requirements of MDR, while all devices already CE cleared will have to comply within four years.

 

The new MDR regulation was supposed to be effective from May 26, 2020, but due to the Covid-19 pandemic and the resulting international economic crisis, it was postponed one year to relieve national health authorities, notified bodies, and medical device manufacturers. A MedTech Summit survey conducted in March 2020 that interviewed companies showed that: 17% of manufacturers consider themselves fully ready to comply with the MDR, 15% say they are “not ready at all,” and 65% say they would have fully exploited the remaining time of the old MDD to be prepared.

 

The new regulation is an opportunity to improve – versus the past – the transparency of technical information on medical devices, thus ameliorating the quality of processes and products.

Synthetic bone substitutes and collagen membranes in dentistry

Reconstructive bone surgery aims to regenerate the loss or resorption of bone through materials and techniques that allow to mimic and activate specific and fundamental reparative mechanisms such as osteogenesis, osteoinduction, and osteoconduction.

 

  • Osteogenesis: formation of new bone tissue by the direct action of progenitor cells and osteoblasts
  • Osteoinduction: regulatory activity of growth factors capable of triggering the differentiation of mesenchymal cells in the osteoblastic lineage and the process of bone regeneration
  • Osteoconduction: support provided by a scaffold that allows the deposition of a new osteoid substance

 

Any regenerative technique must comply with these three elements, together with the vascularization of the treated site and the stability of the graft. When the bone defects are small and the patient is in good health, the bone has an excellent healing capacity, with intrinsic “genesis” and “induction”; it is sufficient that the surgeon fills the void of the loss of substance with grafts or bone substitutes to promote only osteoconduction. This provides the three-dimensional structure to sustain the regeneration process.

Autologous bone is taken from the patient himself and offers many advantages because, in addition to the osteoconductive bone matrix, it can also provide osteogenic and osteoinductive elements thanks to the presence of cells and growth factors. However, the availability of autologous bone in the endo-oral site is limited, while harvesting from other parts of the body (iliac bone) is invasive, risky, and not always possible. In addition to autologous tissue grafting, there are three main categories of bone substitutes: homologous, heterologous, and synthetic.

Homologous bone is from a cadaveric donor. It can be received from tissue banks, but even in this case, various limitations do not always allow its use.

Heterologous bone substitutes are biological grafts derived from animals (usually bovine or equine) that are decellularized and cleared of all antigenic elements. They offer different solutions, in granules or blocks of cortical, or spongy bone, with different resorption and revascularization times. Some heterologous bone substitutes detain a preserved protein/collagen component that can promote rapid osseointegration, as well as indirect osteoinduction.

Synthetic bone substitutes, available in a wide range of different materials, e.g., hydroxyapatites, calcium phosphates and sulfates, have very heterogeneous characteristics usually provide the osteoconductive scaffold for bone neoformation.

 

SpherHA synthetic bone substitutes

 

Tiss’You has developed SpherHA, a line of synthetic bone substitutes, composed of bio-mimetic nano-structured hydroxyapatite. Hydroxyapatite is a mineral found in the inorganic component of human bone. Both the composition and crystal structure of SpherHA are extremely similar to the mineral matrix of our bones, with a calcium to phosphate ratio of 1.67: the same as natural bone apatite.

The highly porous and interconnected structure and its composition ensure an excellent osteoconduction and circulation of nutrients, and also a real active stimulus to the formation of new bone tissue, favoring the processes of cell colonization and early vascularization. The nano-structure of SpherHA crystals provides a very high surface area to volume ratio that ensures complete degradation by osteoclastic activity with consequent remodeling into new viable bone tissue. These elements, along with the bio-mimetic properties, make SpherHA an ideal bone substitute for osseointegration and regeneration of bone defects.

SpherHA is available in several formats: porous chips, dense granules, injectable paste, and moudable crunch. In dental surgery, the indication is for filling small and medium periodontal and peri-implant bone defects, for filling post-extraction sockets, and for sinus lift.

Download SpherHA catalog (PDF)

 

Collagen and GBR (Guided Bone Regeneration)

 

In reconstructive bone surgery, especially in dentistry, it is important to guide bone growth limited to the damaged area, using barrier membranes to prevent the entry of not-osteogenic elements in the treated site. This procedure, called GBR (Guided Bone Regeneration), avoids the infiltration of fibroblasts from adjacent soft tissues, thus preventing the formation of fibrous tissue at the graft site.

For this purpose, Tiss’You has developed Collygen, an absorbable membrane of equine-derived atelocollagen, easily applicable without the need for fixation, for the protection of bone grafts in regenerative surgery techniques. Collygen, thanks to its collagen texture, actively participates in the healing process of the treated site, in addition to its passive protection activity. Recently, it has been demonstrated that the collagen membranes, which in the past were considered only passive barriers, act instead as a real bioactive compartment, interacting with the cellular components that home to the graft site. The processes thus activated contribute to the formation of bone tissue and its improved remodeling.

Download Collygen catalog (PDF)