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The RESTORATION project aimed to develop resorbable bioceramic composite materials for three main applications:

• Osteoarthritis: The project develops functionally gradient bioceramic composite plugs for osteochondral applications.

• Vertebroplasty and Kyphoplasty: a new generation of vertebral cements with appropriate biological, mechanical and rheological properties are being developed.

• Maxillofacial Fracture Fixation: the project develops new bioceramic composites, which will possess sufficient stiffness and strength to protect and support the broken bone.

RESTORATION is a collaborative project targeted to SMEs. It applies knowledge of materials science, mechanical response, processing, clinical delivery and subsequent biological interaction in order to develop new bioceramic products for five research led SMEs partner companies

Resorbable Ceramic Biocomposites for Orthopaedic and Maxillofacial Applications.

Description:JRI Orthopaedics is a UK-based SME with decades of experience of the design and manufacture of highly-successful orthopaedic implants with direct sales across the globe. JRI has close associations with Academia both in the UK and across Europe through its own grant-giving charity.

Role within the project:JRI Orthopaedics takes care of the clinical processes and specification.

Description:Newcastle University is a major regional University in the UK and is internationally recognised for the high quality of its research and teaching. The University is closely integrated into the economic, cultural and social life of the North East of England, and currently has a core student population of around 20,000; with 5,000 staff and an annual turnover in excess of €350m. The groups from Newcastle University collaborating in the project include the School of Mechanical and Systems Engineering, the School of Chemistry, the School of Dental Sciences, and Institute for Cellular Medicine.

Role within the project: The University of Newcastle is the coordinator of the project and takes care of the management and the scientific co-ordination. In addition, the university is responsible for the development and design of the fracture plate device and of the device to treat osteoarthritis, and the materials development for maxillofacial applications.

Description:Sagetis Biotech, was founded in April 2010, as a spin-off of University Ramon Llull, in Barcelona, Spain, but is now privately owned. The company is focused on the development of biomaterials for different applications, from vertebroplasty to drug delivery.The company is now developing new composites formed by a proprietary biodegradable polymer and tailored bioceramics. These composites can be easily injected, can support loads inside the body and at the same time, through controlled biodegradability, induce osteintegration, and sustainably release growing factors.

Role within the project:Sagetis takes care of the development and design of the vertebroplasty and kyphoplasty devices.

Description:Bionica Tech’s mission is to transform innovative ideas into industrial processes, both directly and through partnerships with other companies in the biomedical field. Through Bionica Tech patented ideas acquire a high added value, turning into products tailored to meet the specific requirements of the global biomedical market. Bionica Tech has the exclusive licence of three patents applications related to dental, orthopedics and spinal surgery.

Role within the project:Bionica Tech concentrates on the materials development for vertebroplasty and kyphoplasty applications.Bionica Tech ended its participation in the Restoration project on 31/03/2014.

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PROJECT PARTNERS

Description:Karolinska Institutet accounts for over 40% of the medical research conducted in Sweden.It receives a good share of the government’s strategic investments in advanced research.With its close relationship to the clinical milieu, a well established infrastructure and a stable financial situation, Karolinska Institutet has excellent prerequisites for sustaining high quality research.

Role within the project:The Karolinska Institutet is responsible for the biological enhancement and assessment of the novel biomaterials, which comprises cell culture in the presence of the biomaterial in vitro.

Description:Orla Protein Technologies Ltd is a privately owned company based in Newcastle upon Tyne, UK, the company was formed in 2001 as a spin-out company from Newcastle University. Its key assets are its protein and biosurface expertise, including protein design and manufacture, for biosurface applications. The company has a range of patented, fully-owned technologies that are used to provide bespoke solutions in these fields.

Role within the project: Orla develops proteins to enhance the bioactivity of the resorbable materials.

Description:COREP is a validated SME. COREP’s innovation Centres are the structures where the research conducted by Universities and research Centres find their application and are made available to specific production sectors. Innovation supporter is one of the COREP’s main activities since its inception. The aim consists in disseminating the research and the capacities developed by public research Bodies, making the results available to the business sector, particularly Small and Medium Enterprises.

Role within the project:COREP was added as a beneficiary in the Restoration Project on 01/04/2014 to continue the activities foreseen in WP3 and WP7 on the vertebroplasty cements initially developed by Bionica Tech s.r.l.

Description:LEITAT is a Technological Center specialized in production technologies. LEITAT develops R&D activities in the areas of biomedicine, biotechnologies, environment, surface treatments, materials sciences and renewable energies with deep knowledge and experience in technological transfers to several industrial sectors. LEITAT takes part each year in many projects financed by the regional and national governments, participates in projects co-funded by the European Commission, and develops private R&D projects funded by industrial partners.

Role within the project:LEITAT is taking care of quantification of the environmental impacts of the project developments through life cycle assessment methodology and the dissemination and exploitation of the scientific results.

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PROJECT PARTNERS

Description:The University of Évora, originally founded in 1559 as Colégio do Espírito Santo, was reconstituted in 1973. At the present time, the University of Évora is organized in 4 in schools: Arts, Sciences and Technology, Social Sciences and Nursing and a Doctoral School. These are responsible for all teaching and other skilled services for the community. Offers 33 undergraduate and 41 postgraduate degrees and has about 9.000 students.

Role within the project:The University of Évora is responsible for the biological assessment of medical devices in a large animal model, namely an ovine model.

Description:IQS is a Higher Education Center founded by the Society of Jesus, with over one hundred years of experience (founded in 1905) and an extensive track record and history in the academic field that enable the institution to offer a fully consolidated and proven teaching method. Now belongs to University Ramon Llull the first private University in Spain. Our vocation and social commitment involve educating people in an ethical and integral manner in all personal, academic and professional areas. Due to its scientific tradition, IQS is able to offer thorough training and practical guidance in science and engineering.

Role within the project:In close collaboration with Sagetis, IQS responsibility is the development of biodegradable polymers to be used in the injectable paste and as osteoinductive adhesives for maxillofacial applications.

Description:Far more than just a testing laboratory, Glass Technology Services have been helping companies for over 50 years to design, manufacture and bring glass products to market. From one off projects to long-term consultancy contracts, our team of leading technical experts provide a wide range of bespoke solutions covering all aspects of glass, including: new product development, melting, fitness for purpose, failure assessment, analysis and testing, environmental monitoring and even legal expert witness services.

Role within the project:GTS takes care of the development of materials for osteoarthritis applications.

Description:Candiolo Cancer Institute, FPO – IRCCS, is a comprehensive centre of cancer biomedical research where scientists and physicians work together at the nexus of basic science and clinical research, with a strong focus on translating preclinical discovery into patient benefit. The Interventional radiology unit, since 2002, has performed thousands of vertebral reconstructions with vertebroplasty becoming one of the most experienced teams on this topic. Despite the oncologic mission of the centre, up to 80% of procedures are performed on osteoporotic patients

Role within the project:Candiolo Cancer Institute, FPO – IRCCS takes care of the clinical application of vertebroplasty and kyphoplasty sharing his knowledge on the topic with the other scientists involved in the project.

PROJECT PARTNERS

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OSTEOARTHRITIS (OA)

VERTEBRAL COMPRESSION FRACTURES (VCF)

MAXILOFACIAL BONE FRACTURE

APPLICATIONSBackground Information about the three applications of RESTORATION.

• OSTEOARTHRITIS (OA)

OA is a degenerative joint disease, typified by a loss of quality of cartilage and bone at the interface of a joint, resulting in pain, stiffness and reduced mobility. The process is not confined to the joint but can involve regional muscles and ligaments. Treatment can be considered non-surgical and surgical. Non-surgical treatment includes exercise, weight loss, physical therapy and medication.

For severe disease, when the non-surgical measures cannot control the symptoms, there is currently no other widely recognised treatment other than joint replacement. Survey data indicates that OA affects over 11% of females and 7% of males by the time they reach their mid-fifties, rising with the age. The current global market in joint replacements is estimated to be in excess of €7 billion.

• VERTEBRAL COMPRESSION FRACTURES (VCF)

Increased life expectancy is leading to a rise in age related pathologies which often involve the decay of bone quality (for example from osteoporosis) causing vertebral compression fractures. Approximately 35-50% of women and 20-30% of men develop vertebral compression fractures, and approximately 50% of those affected develop multiple fractures throughout their life. In addition, trauma, bone diseases, and cancers can lead to vertebral fractures and bone loss in younger patients. Vertebral fractures cause pain, disability, spine deformity and worsening of the quality of life. Vertebroplasty (VP) and kyphoplasty (KP) are two minimally invasive procedures that are widely used for the treatment of sympthomatic VCF. VP and KP are performed under radiological guidance. The global market in products for VCF is in excess of €400 million.

• MAXILOFACIAL BONE FRACTURE

Maxillofacial bone fractures occur either as a result of trauma or as part of a surgical procedure designed to correct a developmental fault. Fractures of the mandible account for around 6% of trauma cases, with an increasing incidence of cases seen in the elderly over the last 30 years, and the global market for maxillofacial bone fracture alignment devices is estimated at €100 million.

The limited anatomical space within the maxillofacial region means that fractures of the bones are usually aligned using internal fixation plates, with correct alignment of the bones to allow correct eating, speaking and the quality of life of the patient post operatively. However, there are a significant numbers of revisions required each year due to post-operative problems associated with current plate designs.

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OSTEOARTHRITIS (OA)

RESTORATION seeks to develop early stage interventions for OA, capable of being applied to local defects within the joint, through minimally invasive surgical techniques.

The envisaged process to treat osteoarthritis would require removal of the damaged tissue at the defect site, and the insertion of a small implant to reconstitute the joint. The implant could be designed and created especially for the patient to perfectly meet their needs.

The implant is specified to:

Match the mechanical properties within the scaffold for both bone and cartilage.

Use minimal invasive surgical techniques, and immediate stability, in order that the large majority of treatments are “day case”.

Be able to be augmented by cells, proteins, growth factors, and pharmaceuticals, as appropriate to the clinical application.

Have controlled resorption appropriate to the medical condition.

The scaffold is created in a load bearing bioceramic using 3D printing techniques, with the potential to also create a bioceramic-biopolymer composite structure.

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APPLICATIONS

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RESTORATION develops new injectable bioactive ceramic composites able to stimulate bone regeneration and with the potential to deliver specific drugs to the target site. The bone cement is made of different ceramic composites, which are eventually replaced by the body after they have assisted repair.

The bone cement shows appropriate biological, mechanical and rheological properties.

The paste is easily injectable with a working time (that includes mixing and injection) compatible with surgical procedures (around 8-12 minutes) during which time the paste maintains an appropriate viscosity for injection and cavity filling whilst avoiding cement extravasation into the veins.

After the injection has completed, the cement has a setting time of around 30 minutes, in order to enable rapid recovery and rehabilitation of the patient.

The hardened cement has strength and stiffness similar to those of a healthy vertebral body and is not only osteoconductive but also osteoinductive, so that it can stimulate in-vivo bone regeneration, establishing a strong bond with the surrounding bone.

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VERTEBRAL COMPRESSION FRACTURES (VCF)

APPLICATIONS

MAXILOFACIAL BONE FRACTURE

RESTORATION aimed to develop new bioceramic polymer composites, which can be manufactured to conform to the patient's anatomy, possess sufficient stiffness and strength to protect and support the broken bone, and which resorb non-toxically within 24 months of placement.

The new fracture plate was specified to:Have sufficient stiffness and strength to protect and support the broken bone.

Dissolve non-toxically within 24 months of placement, so that a controlled re-exposure to the mechanical environment is provided to the healing bone, stimulating normal bone remodelling.

Be manufactured to the patient’s anatomy, meaning that the surgeon is no longer required to manipulate the plates to achieve proper bone alignment is achieved.

Be attached using adhesives developed in the project, to the bone-ends without the need for screws, and thus reducing the risk of secondary infection.

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APPLICATIONS

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IMPACT OF THE PROJECTENVIRONMENTAL AND ECONOMIC IMPACT OF THE PROJECT

An environmental and economic assessment of the three types of devices/applications developed in RESTORATION has been performed, considering as a functional unit one device/dose intended to be used in vertebroplasty or kyphoplasty, maxillofacial or osteochondral applications.

A "cradle to gate" scope has been defined including the following stages: material synthesis, manufacturing of the device, sterilisation process, packaging and storage. From the economic point of view the pre-clinic and clinic stages have also been considered.

The environmental analysis has shown that the stages with the largest environmental impacts for all applications are the synthesis of materials and the manufacturing device process, due to their energy consumption.

Regarding the economic analysis, in terms of production costs, the vertebroplasty and kyphoplasty devices are the most expensive. The maxillofacial device has an intermediate production cost and the osteochondral devices have the lowest costs.

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