Biodegradable polyurethane and polyurethane ureas

Abstract

This invention relates to biocompatible, biodegradable thermoplastic polyurethane or polyurethane / ureas comprising isocyanate, polyol and a conventional chain extender and / or a chain extender having a hydrolysable linking group and their use in tissue engineering and repair applications, particularly as stents and stent coating.

Description

FIELD OF THE INVENTION [0001] The present invention relates to biodegradable processable and preferably thermoplastic polyurethanes or polyurethane / ureas and processes for their preparation. The polymers are biodegradable, processable and preferably thermoplastic which makes them useful in biomedical applications including, for example, in the fabrication of scaffolds for tissue engineering applications. The invention particularly relates to the use of such polyurethanes and polyurethane / ureas in fabricating scaffolds using rapid prototyping techniques. BACKGROUND TO THE INVENTION [0002] Biodegradable synthetic polymers offer a number of advantages over other materials in various biological applications including tissue repair. For example, in relation to the development of scaffolds in tissue engineering, the key advantages include the ability to tailor mechanical properties and degradation kinetics to suit various applications. The simple and routine fabrication of scaffolds with ...

AI Technical Summary

Benefits of technology

[0030] Throughout this specification, the term “chain extender” should be taken to mean a low molecular weight compound having two or more functional groups that are reactive towards isocyanate and having a molecular weight of less than 350. Chain extenders include functional monomers with degradable arms. The chain extender may be employed to introduce easily degradable hard segment components into the polyurethane or polyurethane / urea structure. Incorporating such chain extenders allows preparation of easily degradable polyurethanes with fewer degradation products. For example, polyurethane based on ethyl-lysine diisocyanate and glycolic acid based polyol and chain extender degrades to bioresorbable glycolic acid, lysine, ethylene glycol and ethanol.

[0035] It has been found that the polyurethanes and polyurethane / ureas according to the invention form porous or non-porous cross-linked or linear polymers which can be used as tissue engineering scaffolds, and may be used in rapid prototyping techniques including FDM. It has also been found that certain of the biodegradable polyurethanes according to the invention exhibit a glass transition between room temperature and 37° C. This property can be used to extrude hard materials on FDM apparatus (going in at 20° C.) which will soften and even become elastomeric in vivo or while growing cells on scaffolds in a bioreactor at physiological temperatures of 37° C. This is also a very useful property for soft tissue applications.

[0036] The polyurethanes and polyurethane / ureas can be sterilized without risk to their physical and chemical characteristics, preferably using gamma radiation to ensure sterility.

Problems solved by technology

Many of the currently available degradable polymers do not meet all of the requirements to be used in such applications.

Most biodegradable polymers in the polyester and ester family, for example, are hydrophobic in nature and as such, only a limited number of drugs can be incorporated into such polymers.

However, shaping these scaffolds to fit cavities or defects with complicated geometries, to bond to bone tissue, and to incorporate cells, drugs and growth factors, and the requirements of open surgery are a few major disadvantages of the use of known scaffold materials.

However, these polymers have a number of disadvantages, including rapid loss of mechanical properties, long degradation times, difficulty in processing, and the acidity of degradation products resulting in tissue necrosis.

These polymers, when used in biodegradable stents, have to be heated during the deployment process to temperatures as high as 70° C. which can cause cell damage.

All of these methods have disadvantages including that: they require a mould to shape the scaffold—this is costly and can only produce a single shape; these methods offer little or no control over the orientation of the pores and degree of interconnectivity; usually a polymer skin forms on a moulded scaffold (even if it is porous) which can require extensive post-synthesis treatment; and some of the methods of scaffold fabrication such as phase separation and porogen leaching often involve the use of toxic organic solvents which is undesirable.

Most synthetic biodegradable polymers do not meet the requisite property requirements.

In short, the use of rapid prototyping machines to make porous, highly controlled and interconnected tissue engineering structures requires a complex combination of various techniques including polymer chemistry, polymer processing, rapid prototyping and tissue engineering and, accordingly, is particularly complex.

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