Calcium phosphate cements and foams: characterization of porosity and use as local drug delivery devices

• Autores: David Pastorino
• Directores de la Tesis: Cristina Canal Barnils (dir. tes.), Maria Pau Ginebra i Molins (codir. tes.)
• Lectura: En la Universitat Politècnica de Catalunya (UPC) ( España ) en 2015
• Idioma: español
• Tribunal Calificador de la Tesis: Mariano del Pilar Ignacio Fernandez Rodriguez Fairén (presid.), Montserrat Español Pons (secret.), Sylvain Mille (voc.)
• Materias:
  • Ciencias tecnológicas
    • Tecnología de materiales
      • Materiales cerámicos
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• Resumen

  • The topic of this Philosophy Doctor Thesis tallies with the national project MAT2012 of the BBT group of UPC: "Pore4Bone: Biomimetic calcium phosphates: tailoring porosity from the nano- to the macroscale for osteoinduction, drug delivery and bone tissue engineering". Bone is one of the most transplanted tissues globally, with around one million surgical procedures each year. Ageing of the population worldwide requires intense effort in designing efficient, clinically applicable multifunctional biomaterials for bone regeneration. The need for a higher volume of bone graft, and advanced solutions make synthetic bone grafts an attractive alternative to auto- or xenografts. Synthetic calcium phosphate cements (CPCs) provide a high freedom of processing and conformation, and excellent biomimicry to natural bone. Biocompatible and osteoconductive per se , CPCs support in vivo remodeling of bone. The intrinsic micro- and nano- porosity of CPCs resulting from the spaces between the entangled crystals and aggregates once set is a key property when considering bone regeneration and local release of drugs. It provides free space for drug diffusion and fluid penetration, both of which are essential elements for drug release. Thus, a comprehensive characterization of the porosity, especially at the microscopic and nanoscopic scale is of paramount interest to identify these mechanisms, so it has been tackled in detail in this work. Focusing on bone infections, the combination of antibiotics with osteogenic matrices like CPCs is explored in the PhD Thesis. Indeed, while bone infections and bone disorders are generally treated post-operatively by systemic administration of the indicated antibiotic, achieving a therapeutically efficient local delivery of the active principles is a key challenge, as it allows reducing secondary unwanted effects, drug interactions and diminishing the required dose due to the enhanced local bioavailability. In particular, the relationship between antibiotic addition, porosity and drug release in calcium phosphate cements (CPCs) is highlighted and studied in this PhD Thesis. Finally the introduction of macropores in CPCs is investigated to manufacture antibiotic-releasing calcium phosphate foams (CPFs) for bone regeneration, which present clear clinical benefits over CPCs as multifunctional biomaterials. Indeed, the clinical performance of CPCs as local drug delivery devices is restricted by the relatively low penetration of corporal fluids through their micro or nanopores, preventing a complete release of the drug. The slow release of the entrapped antibiotic during the degradation of the CPC may generate a local concentration below the minimum inhibitory concentration, with the risk to foster the development of antibiotic-resistant bacteria. The addition of a network of interconnected macropores in CPCs represents a major advance by enhancing fluid circulation, and the consequent increase of the release rate of the antibiotic. Thus, in addition to the injectability and biomimicry of CPCs, the interconnected macroporosity of CPFs endows these materials with clear advantages not only in terms of tuning the release kinetics of active principles, but also when considering their excellent osteogenic properties.