Wspólnotowy Serwis Informacyjny Badan i Rozwoju - CORDIS

FP6

RESPOLMED Streszczenie raportu

Project ID: 500919
Źródło dofinansowania: FP6-MOBILITY
Kraj: United Kingdom

Final Activity Report Summary - RESPOLMED (Bioresorbable Polymers for Medical Applications)

Bioresorbable polymers for in-vivo biomedical use are heavily dominated by polylactides (PLA) and polyglycolides (PGA). However, current implant polymers based on PLA and PGA are not ideal for hard and soft tissue fixation because of their sudden loss of mechanical properties on degradation process with no continuum of change from inelastic to elastic behaviour. The aim of the project was the preparation of flexible materials based on biodegradable graft copolymers consisting of polyoxanorbornene backbones with PLA side-chains which degrade in such way that their mechanical properties change gradually from a rigid to flexible material before bioresorbtion is complete. A series of novel biodegradable/bioresrobable graft copolymers with different length of polyoxanorbornene backbones with poly(hydroxyacid) side-chains, were synthesised to study the variation in properties of these polymers as a function of degradation under simulated biological conditions. A series of mono- and di-alcohol substituted oxanorbornenes were synthesised and used as initiators for the ring opening polymerisation (ROP) of lactide in the presence of stannous octoate, Sn(Oct)2 to prepare oxanorbornenyl polylactide (PLA) macromonomers. The well-characterised macromonomers were then subjected to ring opening metathesis polymerisation (ROMP) by three well-defined 1st, 2nd and modified 2nd generation Grubbs ruthenium initiators to prepare the target bioresorbable graft copolymers. The most effective Grubbs ruthenium initiator for the ROMP of the macromonomers was found to be the modified 2nd generation ruthenium initiator.

Investigation of the target graft copolymers by Size Exclusion Chromatography and NMR spectroscopy showed the presence of some uncapped PLA homopolymer (not attached to an oxanorbornyl group), produced as a side product during the ROP of lactide. Our investigation showed that the presence of PLA homopolymer impurity in the target graft copolymers significantly increases the rate of degradation of the final material. Therefore, we developed a convenient procedure of graft copolymers purification to remove PLA homopolymer from the samples.

The target graft copolymers were subjected to degradation in phosphate buffer solution. The degradation studies at two different temperatures, 37C and 50C showed that, as expected, increasing the temperature significantly increased the rate of degradation. Comparison of degradation behaviour of graft copolymers with the same oxanorbornyl backbone and different length of PLA grafts indicated that samples with shorter PLA grafts degrade more slowly. The results also indicated that target graft copolymers with one PLA side chain exhibit fastest rate of degradation. One explanation is that the presence of two PLA side chains on each five membered ring in the backbone chain induces steric hindrance and therefore reduces the rate of degradation.

The materials based on pure PLA homopolymer show 80% weight loss in about 80 days whereas the weight loss of our target graft copolymers is 40% over the same time. This clearly demonstrates that the rate of degradation of the PLA is greatly reduced by attaching them (grafting) to a polyoxanorbornene backbone chain. This concept of retardation of degradation was the main objective of this work which has been successfully achieved. The medical device industry as a whole can benefit from the outcome of the research and synthesis of a new class of materials from which to fashion devices for patient benefit.

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