Regeneration is better than substitution

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In Europe, people aged more than 50 years old are about 150 million. Prevention, care and cure regarding aged people are core concerns for European Commission. Among the chronic pathologies, osteoarthritis is the second disease in Italy. It has high prevalence in the population older than 65 years, but the prevalence in younger age groups appears to be on the increase.

In Italy, osteoarthritis affects 16.4 percent of people with more than 65 years. According to the “Annuario statistico Italiano 2013” an ISTAT survey, 30.4 percent of women older than 65 years and 50% of men have ingested drugs to counteract osteoarthritis in 2012. As reported by the “Expert's consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCE) the economic cost of osteoarthritis is considerable. The total expenses relating to the treatment of osteoarthritis are estimated at between 1% and 2.5% of the gross domestic product (GDP) for westernized countries. Moreover, according to Piscitelli paper, loss of working days in patients aged less than 65 years was estimated between 805,000 and 1 million days. Osteoarthritis is associated with productivity losses in individuals who are employed. The growing demand for elective surgery for joint replacement, particularly from relatively younger age groups, drives the need for more long-lasting solutions. 

OPHIS deals with osteoarthritis

Creating a biomaterial able to substitute and then regenerate damaged bone and cartilage. This is the OPHIS “composite phenotypic triggers for bone and cartilage repair” project ambition. OPHIS was designed with the aim to develop new engineered biomaterials for the repair and regeneration of both osteochondral and osseous tissues, when degenerative articular or bone diseases – as osteoarthritis or osteoporosis – Impair the mechanical and physiological function.

The Institute of Science and Technology of Ceramics (ISTEC-CNR) is leading the project, starting from 25 years of experience in biomedical devices creation. OPHIS has been granted from FP7-NMP  of the 7th European Framework Programme, with 3,939,708 euros. European funds, covering a period of four years, sustained the work of 18 researchers in different subjects engaged: physics, chemistry, material engineering and biology. The ISTEC project involves Italian partners (Rizzoli Institute, UCSC and Fin-Ceramica Faenza), but includes also French, German, English and Swiss research centres.

Biomaterials created by OPHIS are generated starting from collagen fibres self-assembly associated with a biomineralization process, mimicking that occurring during bone formation. “In comparison with previous materials created by our laboratories,” highlights Anna Tampieri, the project coordinator, “the new scaffold is able to beckon cells into the 3D structure without any external stimulus. Cells recognize the injected material as a self and natural substrate. Thus cells colonise and mould material, to restore natural tissue within one year.”

Using constructs with cells originated from patients guarantees the highest regenerative capacity. However, the national and European laws discourage the clinical use of materials carrying stem cells. Thus, the body cells attraction is now preferred. In ISTEC laboratory specific growth factors and chemical or biochemical cues has been assessed, bound to new polymers to achieve an excellent cell attraction and differentiation. The simplest OPHIS material has been already developed and tested to osteoarthritis treatment. Osteoarthritis is the most common joint disease and is characterised by the progressive deterioration and sclerosis of articular cartilage and sub-chondral bone. A basic scaffold has been tested on 100 patients spread in different European centres with surprising regenerative capacity.

However, the present research improved both the functional molecules and the polymeric scaffold with cellulose, alginate and chitosan polymers. “We have already made a request for Horizon 2020 funds, to perform clinical tests,” adds Anna Tampieri. “In fact the last developed materials promise more mechanical stability, and more cell-homing capacity.”

The future of osteoporosis

The OPHIS study offers a second perspective: the osteoporosis treatment. Osteoporosis is characterised by decreased bone mass and bone mineral density, leading to bone fragility. Osteoporosis, with osteoarthritis, has a significant economic and societal impact in elder citizens. In Italy, osteoporosis is the fourth chronic disease. 7.4% of people older than 65 years suffer for this pathological condition. According to EU27 Report, due to the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA), 22 million women and 5.5 million men were estimated to have osteoporosis.  The economic burden of incident and prior fragility fractures was estimated at € 37 billion. And the costs are expected to increase by 25 % in 2025.

Vertebral bodies are the first damaged by an osteoporosis degeneration. In the year 2000 there were an estimated 9 million osteoporotic fractures world-wide of which 1.4 million were clinical vertebral fractures. The modern medicine tries to offer solutions, but tissue replacement is not able to restore completely the patient's mobility. The most common solution- acrylate cements - stalls full movements and induces necrosis and other vertebral bodies fracture. The new material created in Tampieri's laboratory is a biomimetic scaffold, able to host cells. The materials are conceived to set and harden in contact with physiological fluids in short times (less than 20 minutes). The ceramic pastes are highly injectable in aqueous media. In rabbit, bone regeneration occurred within 3 months, thus with a high speed strengthening capacity. With Horizon 2020 funds, experiments will carry on greater size animals. Moreover scaffolds, when doped with Strontium, exhibited in vitro bioactivity. Thus their potential use could be the development of biomedical devices with anti-osteoporotic functionality.

The final goal of this research could be the substitution of metallic prosthesis. If scaffold reaches a greater mechanical stability, bone will be regenerated and not only substituted. “We built these projects on our activity, interest and business”, Anna Tampieri concludes. “This assures a tight-knit team and the target achievement”.

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