Injectable degradable composite materials for bone repair and drug delivery.
Doctoral thesis, UCL (University College London).
The aim of this project was to develop injectable materials to repair damaged bone and, to simultaneously release antibacterial drugs and genes in a controllable manner. Fluid poly (propylene glycol -co- lactide) dimethacrylate (PGLA-DMA) was first synthesised and then filled with varying levels of β- tricalcium phosphate (β-TCP) and monocalcium phosphate monohydrate (MCPM) to fabricate composite materials. For all formulations (including polymer and composites), full methacrylate conversion was found to occur within 200 s of exposure to blue light. The initial dry polymer modulus was enhanced three-fold by increasing total filler content to 70%. After composite immersion in water, β-TCP and MCPM was found to react and re-precipitate within the set materials as dicalcium phosphate (DCP, i.e. brushite and monetite). At higher MCPM levels there was an increase in DCP formation, composite degradation rate, release of both calcium and phosphate ions and buffering of acidic polymer degradation products. Additionally, bone-like MG-63 cells were found to attach, spread and proliferate on both the polymer and the composite surfaces and, composites implanted into chick embryo femurs demonstrated close apposition to the host tissue. To examine the potential value for drug delivery, both the polymer and the composites were prepared containing 10% of the antibacterial chlorhexidine (CHX). The drug was found to be released from material via diffusion, which increased along with antibacterial activity when the filler content was raised. PGLA-DMA polymer was additionally prepared containing complexes of the commercial cationic lipid MetafecteneTM Pro and green fluorescent protein plasmid DNA. Initial studies demonstrated that the components released from the materials were capable of gene transfection into human bone-forming mesenchymal stem cells in vitro. These studies thus demonstrate that the injectable, rapidly settable PGLADMA materials produced here might have clinical potential as both bone adhesives and drug delivery devices.
|Title:||Injectable degradable composite materials for bone repair and drug delivery|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Eastman Dental Institute > Biomaterials and Tissue Engineering|
Archive Staff Only