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Bioactive resorbable scaffolds for drug delivery in bone tissue engineering

Final Report Summary - BIORESS (Bioactive resorbable scaffolds for drug delivery in bone tissue engineering)

Bone replacements are frequently required to substitute damaged tissue due to any trauma, disease or surgery. The current therapies for bone grafts: autografts (taken directly from the patient), allografts (taken from a cadaver donor) or xenograft (taken from animals), are limited in availability and can be associated with patient morbidity or with the risk of inducing transmissible diseases. The development of synthetic tissue-engineered bone scaffold substitutes is one of the most important topics in the bone tissue engineering field.

A bone scaffold is a three-dimensional (3D) porous structure that can be used as a bone graft or bone filling material. It should have good mechanical properties to support the structural loads and high porosity to allow tissue in-growth and vascularisation, cell adhesion, migration and proliferation.

Scaffolds made of phosphate glasses are an attractive solution. Phosphate glasses are resorbable and the degradation kinetics can be controlled by their composition. They are biocompatible, bioactive (has ability to develop a chemical bond with the newly formed bone tissue, by precipitation of hydroxylapatite (HA) layer similar with the one found in natural bone) and osteoconductive (has ability to support bone growth over its surface), making them useful as bone fillers and drug delivery systems.

The aim of this project was the development, characterisation and in vitro experimentation of novel macroporous scaffolds with highly interconnected porosity and controlled biodegradability for drug delivery in bone tissue engineering. The main objectives of this project were:
1. synthesis and characterisation of bioactive and bioresorbable phosphate glasses;
2. synthesis and characterisation of bioactive and bioresorbable scaffolds;
3. in vitro biological characterisation of the scaffolds.

Phosphate glasses belonging to the complex system P2O5-SiO2-Na2O-CaO-MgO-K2O were obtained by a traditional melting and quenching method. They were then characterised in terms of microstructure, solubility and bioactivity. The results show that the glass is bioactive (a HA layer is formed on the glass surface after immersion in a SBF) and bioresorbable. It lost almost 76 wt.% after 4 months of immersion in distilled water. The dissolution takes place by a congruent surface erosion mechanism.

The glass was further used to produce macroporous 3D-scaffolds for bone regeneration. The scaffolds were fabricated by using the burning-out method. This method, involves the use of an organic phase as porogen, which is mixed with inorganic particles (the glass powder in this case). The mixture is pressed, obtaining a green body, and then it is heat treated to remove the organic phase (by burning) and to sinter the inorganic particles. The heat treatment process was optimised in order to provide a better control of the scaffold microstructure and to enhance the mechanical properties. The obtained scaffolds were characterised in terms of microstructure, solubility, bioactivity and mechanical strength. Biocompatibily was evaluated in vitro, using human marrow stromal cells.

The results show that the obtained scaffolds have a porosity of 80-90 vol%, with a high degree of interconnection. The maximum compressive strength was 2 ± 0.5 MPa. After 4 months of soaking in SBF, the scaffolds lost almost 76 wt.% with a pH not exceeding the 7.45 value. Morphological and biochemical assays with human marrow-derived stromal cells seeded on scaffolds showed that the cells maintain their metabolic activity and ability to proliferate on the scaffolds.

To conclude, during this project, a new bioactive and bioresorbable phosphate glass was produced and characterised. This glass was then utilised to produce bioactive and bioresorbable scaffold with highly porous structure and interconnected porosity for bone tissue engineering. It has shown a stimulatory effect in promoting osteogenesis.

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