New approaches in calcium phosphate cements and ceramics for bone regeneration.

Resumo

Bone is among the most frequently transplanted tissues in the body. In Europe, about one million patients encounter a surgical bone reconstruction annually. The worldwide market of bone replacement materials is currently estimated at 5 billion Euros, with a 10% growth due to the ageing of the population. Natural grafts present several drawbacks which pushed scientists to investigate synthetic biomaterials. Although most synthetic bone substitutes available possess some of the positive properties of autografts, none yet have all the benefits of one's own bone. Among the available biomaterials, Calcium Phosphates (CaPs) are of great interest. Nonetheless, these materials can still be improved in several respects. The main aim of this PhD Thesis is to contribute to the improvement of the properties of CaPs for bone regeneration with primary regard to Calcium Phosphate Cements (CPCs). The Thesis is divided in three main parts: i) Biphasic Calcium Phosphate Cements (BCPCs) with modified solubility and ion release; ii) Fibre Reinforced Calcium Phosphate cements (FRCPCs) with improved mechanical properties; iii) Macroporous CaP scaffolds for simvastatin acid release. In the first part novel biphasic CDHA/ß-TCP cements were obtained by mixing two Tricalcium Phosphate (TCP) polymorphs with different solubility (a-TCP and ß-TCP) at different a-TCP/ß-TCP ratios, and characterised in terms of setting properties, mechanical properties, and degradation. In the second part of this manuscript, new FRCPCs were fabricated with a focus on improving the adhesion fibres/matrix, in order to enhance the load transfer and, thus, the toughness of the material and their physico-chemical properties were investigated. Different approaches were studied. The first approach was to increase the chemical affinity of the fibres towards the matrix, adding an element in the matrix with high affinity to the fibres. In the first approach, TryMethyl Chitosan (TMC) was introduced in the liquid phase of a matrix reinforced with chitosan fibres. In the same line, lactic acid (LA) was added in the liquid phase of cements reinforced with Poly-L-lactic acid (PLLA) yarns. The biological characterisation of FRCPCs was explored using human osteoblastic-like cells MG63 . Another approach was to investigate the potential of low temperature plasma surface modification of PLLA yarns for reinforcement of CPCs. Oxygen low pressure plasma was employed at different treatment times and the surface properties of the untreated and plasma-treated PLLA were evaluated. The third part of this Thesis consisted in producing low temperature (CDHA) or high temperature (ß-TCP) macroporous scaffolds as carriers for Simvastatin acid (SVA), an osteogenic and angiogenic promoter. In order to modulate the drug release beyond the intrinsic capacity of the material, plasma polymerisation with PCL:PEG copolymers was used to dry-coat the CaP scaffolds. The material properties, the plasma polymer layer and the drug release from the scaffold were characterised.