Porous calcium phosphate granules for biomedical applications

The repair or replacement of damaged or diseased hard tissue is a biomedical field that has been the subject of more and more interest in many areas of research and especially in the development of new biomaterials. The rise in the average age of the world population, increasing osteoporosis treatments and the spread of cancer and genetic bone diseases, has brought about the need to find solutions for patient care. To achieve this target/objective, biomaterials must simulate the body environment as much as possible and favour tissue repair by integrating them into the host site. Calcium phosphates are used as medical implants because they have a chemical composition similar to the mineral of human bones, i.e. apatite. For this reason they are biocompatible and they can interact in a bioactive way with bone tissue. In the present work a specific form of bone graft, in the form of calcium phosphate granules, has been developed by using the droplet extrusion technique. The granules were characterized chemically and physically, with specific attention to in vivo and in vitro analyses. The proposed method has allowed us to obtain spherical granules in very narrow micrometric size distribution (300-1200 μm) without the use of solvents or oils thus avoiding time consuming washing processes. Granules were produced with several controlled mineralogical compositions including: pure Hydroxyapatite (HA) and β-Tricalcium Phosphate (βTCP), mixtures of HA/βTCP and Hydroxyapatite/Tetracalcium phosphate (HA/TTCP), and compositions doped with zinc (for antibacterial purposes) and strontium (for anti-osteoporosis purposes). Of several interesting features, the produced granules show high interconnected microporosity (0.1-10 μm) and surface roughness, properties necessary for osteoconductivity. The solubility behavior of granules was studied and demonstrated that the morphology and microporosity are more important in dissolution processes than chemical or mineralogical composition. Products were tested in simulated body fluid (SBF), and among the different compositions, HA/TTCP has been found to be bioactive during in vitro studies. In fact an intense precipitation of a carbonated layer of apatite was observed, associated with the high dissolution of a TTCP phase. All pure granules were demonstrated to not be cytotoxic. Bone implantations in different animal models (rabbits and primates) showed good performance of granules in the repairing of bone. The granules stimulated the bone growth without any inflammatory reactions. In particular, HA/TTCP granules exhibited excellent biomechanical properties by increasing the stability of neo-formed bone. These preliminary investigations were sufficient to show that the developed granules can be used for bone repair or replacement. However, more studies, especially for doped products, such as in vitro cells experiments, have to be performed to assure the biocompatibility and the effective stimulation of bone growth. This work was performed in collaboration with Eurocoating S.p.A. (Trento, Italy), a company expert in biomedical coatings for prostheses and implants, and it is a part of “CaP project†co-sponsored by Provincia Autonoma di Trento (Italy).