Publications

The purpose of the present work was to evaluate in vivo different antimicrobial therapies to eradicate osteomyelitis created in the femoral head of New Zealand rabbits. Five phosphate-based cements were evaluated: calcium phosphate cements (CPC) and calcium phosphate foams (CPF), both in their pristine form and loaded with doxycycline hyclate, and an intrinsic antimicrobial magnesium phosphate cement (MPC; not loaded with an antibiotic). The cements were implanted in a bone previously infected with Staphylococcus aureus to discern the effects of the type of antibiotic administration (systemic vs. local), porosity (microporosity, i.e. <5 μm vs. macroporosity, i.e. >5 μm) and type of antimicrobial mechanism (release of antibiotic vs. intrinsic antimicrobial activity) on the improvement of the health state of the infected animals. A new method was developed, with a more comprehensive composite score that integrates 5 parameters of bone infection, 4 parameters of bone structural integrity and 4 parameters of bone regeneration. This method was used to evaluate the health state of the infected animals, both before and after osteomyelitis treatment. The results showed that the composite score allows to discern statistically significant differences between treatments that individual evaluations were not able to identify. Despite none of the therapies completely eradicated the infection, it was observed that macroporous materials (CPF and CPFd, the latter loaded with doxycycline hyclate) and intrinsic antimicrobial MPC allowed a better containment of the osteomyelitis. This study provides novel insights to understand the effect of different antimicrobial therapies in vivo, and a promising comprehensive methodology to evaluate the health state of the animals was developed. We expect that the implementation of such methodology could improve the criteria to select a proper antimicrobial therapy.

JTD Keywords: Calcium phosphate cements, Calcium phosphate foams, Drug delivery, In vivo, Magnesium phosphate cements, Osteomyelitis

The application of minimally invasive surgical techniques in the field of orthopaedic surgery has created a growing need for new injectable synthetic materials that can be used for bone grafting In this work a novel fully synthetic injectable calcium phosphate foam was developed by mixing alpha-tricalcium phosphate (alpha-TCP) powder with a foamed polysorbate 80 solution Polysorbate 80 is a non-ionic surfactant approved for parenteral applications The foam was able to retain the porous structure after injection provided that the foamed paste was injected shortly after mixing (typically 2 5 min), and set through the hydrolysis of alpha-TCP to a calcium-deficient hydroxyapatite, thus producing a hydroxyapatite solid foam in situ The effect of different processing parameters on the porosity. microstructure, injectability and mechanical properties of the hydroxyapatite foams was analysed, and the ability of the pre-set foam to support osteoblastic-like cell proliferation and differentiation was assessed. Interestingly, the concentration of surfactant needed to obtain the foams was lower than that considered safe in drug formulations for parenteral administration The possibility of combining bioactivity, injectability, macroporosity and self-setting ability in a single fully synthetic material represents a step forward in the design of new materials for bone regeneration compatible with minimally invasive surgical techniques.

JTD Keywords: Calcium phosphate cement, Hydroxyapatite foam, Scaffold, Surfactant, Injectable material

The design and processing of 3D macroporous bioactive scaffolds is one of the milestones for the progress of bone tissue engineering and bone regeneration. Calcium phosphate based ceramics are among the most suitable materials, due to their similarity to the bone mineral. Specifically, beta-tricalcium phosphate (beta-TCP) is known to be a resorbable and bioactive material, with well established applications as bone regeneration material. The aim of this work is to explore a new OF route to obtain beta-TCP macroporous scaffolds starting from calcium phosphate cements. To this end foamed calcium phosphate cement.. composed of alpha tricalcium phosphate as starting powder was used as initial material. The set foamed structures, made of calcium deficient hydroxyapatite (CDHA) were sintered to obtain the final beta-TCP macroporous architecture. The interconnected macroporosity was maintained.. whereas the porosity in the nanometric range was strongly reduced by the sintering process. The sintering produced also an increase in the mechanical properties of the scaffold.

JTD Keywords: Calcium-phosphate ceramics, Cements, Scaffolds, Foams, Macroporous, Tissue engineering