Final Report Summary - SMARTCAP (Injectable macroporous biomaterial based on Calcium Phosphate cement for bone regeneration) The 'Injectable macroporous biomaterial based on calcium phosphate cement for bone regeneration' (SmartCaP) project was conceived to introduce a novel concept of biomaterials for bone repair and regeneration. These biomaterials should be multifunctional, injectable, self-setting, macroporous, 'intelligent', biodegradable, easy to apply and sterilisable. To respond to all these requirements, the project was divided in seven workpackages (plus one regarding management issues).WP 1: Material design, fabrication and characterisationThe main objectives of this workpackage were to modify chemically a calcium phosphate (CaP) bone cement to make it self-setting, intelligent, injectable, and multiporous (macro, micro and nano) and to characterise it.WP 2: Functionalisation for improved osteogenesis and angiogenesisBiological and chemical modifications of the biomaterials were performed in order to enhance bioactivity. An improvement in cell attachment to the material through integrins was used to modulate cell signal transduction cascade regulating gene expression.WP 3: Biological molecules loading and delivery assaysMaterials developed in WP 1 were loaded with growth factors and drugs. Liberation studies were performed in order to assess the mid-term release of the biological entities.WP 4: Isolation and culture of primary cellsIsolation and expansion of primary osteoblasts, osteogenic progenitor cells, osteoclasts from human tissue and endothelial cells from immortal cell line were performed and seeded on materials. Mesenchymal cells from bone marrow were induced to differentiate into osteoblasts, and seeded onto materials. Morphology, biochemistry, and bone forming ability of cells interacting with materials will be analyzed. Gene expression of the cell / material construct was also analysed.WP 5: In vitro effect of mechanical stimuli on biomaterial biological performanceThe effect of mechanical stimuli when applied on the scaffold in a bioreactor has been investigated. The materials developed were tested in conditions that mimic as closely as possible the in vivo conditions. Moreover, the release of ions during cell proliferation and differentiation was monitored in situ through biosensors.WP 6: Computer simulations of bone regenerationThroughout the project, this workpackage has been used in parallel with the experimental tasks in order to give complementary to the experimental results and to get a different approach of implementing the proposed strategy. Computer models were used to help designing the mechanical requirements of the biomaterials developed in WP1. Computer simulations were performed to model the release over time of growth factors and drug delivery. The interaction of the mechanical stimuli with the biological processes on the biomaterials was analysed through a mechanoregulation model. Moreover, a device for injection was designed and fabricated for all materials.WP 7: In vivo biomaterials evaluation: investigation of biocompatibility and osseointegrationFollowing the results obtained in WP4 and WP5, selected biomaterials were implanted in vivo in rabbits. The performance of the biomaterials was evaluated at month 1, 3, and 5. This workpackage has served as a prototype study that demonstrate the feasibility of the projected breakthrough.Expected end resultsThe main goal of this project consists in the implementation of the concept of 'intelligent' injectable self-setting biodegradable macro-micro porous biomaterials, promoting angiogenesis and osteogenesis, for bone regeneration.Intentions for use.These 'intelligent' biomaterials are intented to solve problems related to osteoporosis, bone tumours, spinal disorders, severe trauma to the extremities, crippling diseases, deformities in children and fracture healing, affecting hundreds of thousands of people in Europe and worldwide.ImpactThe project will have impact on European quality of life by: - raising the number of patients who can be treated- reducing the costs related with bone treatments with increasing quality- introducing new therapeutic substances such as growth factors and differentiation agents- generating new processing methodologies that can be used on other types of industries- generating high level knowledge that will be used by the different high education institutions to teach their students- reducing patient discomfort in all aspects- creating new job positions directly and indirectly related to the project- widening the market for European companies in the field of biomaterials for tissue replacement and regeneration systems.Summary of resultsComposite materials based on CaP cements have been functionalised to improve cell adhesion and seeded with growth factors and drugs to make them multifunctional. Moreover, an injecting device has been designed to improve the minimally invasive surgical technique.In parallel, computer models have been developed to optimise the biomaterial and obtain a better understanding of the interactions between mechanical and biological processes. The resulting biomaterials have been tested in vivo, showing their regeneration function. A patent is being prepared as a previous step to the commercialisation of these biomaterials.Dissemination and useUnfortunately the preparation of the patent has taken a long time given that there are four institutions involved and that project partners wanted to include the beneficial effect of the biomaterials shown in the in vivo experiments, which ended by the end of the project. This fact has so far hindered the dissemination of the project. Nevertheless, several dissemination activities were performed:1. Set up and updating of project website: http://www.smartcap.eu 2. Publications of three issues of project newsletter, http://www.smartcap.eu/newsletter3. Design of a logo of the project4. Conferences:- Bioengineering in Ireland Conference, 27 - 28 January 2006, Galway (Ireland). Title: 'Effect of scaffold porosity on bone regeneration- 5th World Congress of Biomechanics, 29 July 4 August 2006, Munich (Germany). Title: 'Optimisation of bone scaffold porosity using mechanobiological simulations' - 20th European Conference on Biomaterials, 27 September - 1 October 2006, Nantes (France). Title: 'Optimisation of sterilisation conditions of biodegradable, bioactive soybean-based biomaterials'.- Soy and Health Conference 2006, 12-13 October 2006, Düsseldorf (Germany). Title: 'Optimisation of sterilisation conditions of biodegradable, bioactive soybean-based biomaterials'. Related documents Final Report - SMARTCAP (Injectable macroporous biomaterial based on Calcium Phosphate cement for bone regeneration)
