An ideal adhesive for bone repair : Injectable, rapidly crosslinkable, biodegradable poly(esters) containing reactive calcium phosphate fillers.

Developing an ideal adhesive for bone repair is a difficult but potentially highly rewarding challenge requiring expertise from several scientific disciplines. Such an adhesive should be able to be injected into a damaged site but then set rapidly to give a material of high strength and comparable flexibility to bone. Provided the adhesive can spread into the tissue the setting reaction would provide adhesion (micromechanical) and thereby early support for the surrounding bone. The material should then, however, degrade providing components that can be converted by cells to new bone. This degradation could additionally provide slow release of drugs that enhance repair or prevent infections. Current poly(methylmethacrylate) (PMMA) bone cements can be rapidly set but are non degradable. Conventional long chain poly(esters), presently used as degradable bone screws and various other medical applications, lack injectability and thereby adhesion or the ability to be used in minimally invasive arthroscopic procedures. Conversely, although calcium phosphate cements are injectable and provide the elements required for the inorganic component of bone their setting characteristics are difficult to control particularly in an aqueous environment and their mechanical properties are far from ideal. One aim of this project is therefore to chemically combine ester and methacrylate structures to produce polymer molecules that are sufficiently short to be fluid but that can crosslink through the methacrylate groups within seconds of light exposure providing a high strength adhesive like PMMA. One challenge will be assessing exactly how to vary the chemistry of the materials to ensure the material can degrade after set at the rate at which bone could reform. This degradation will occur through the poly(ester) segments leading to components that can readily be removed by the body. To provide the elements required for bone repair, the fluids can be filled with high percentages (>70wt%) of micron dimension calcium phosphate particles. A unique method employed in this proposed study that improves the dispersion of these particles within the polymer involves using calcium phosphates that react with water via the same process that sets conventional calcium phosphate cements. What is intriguing is that we can get this reaction to be catalysed by water that the set polymer absorbs from its surroundings. The absorbed water dissolves the calcium phosphates, enables them to react but then reprecipitate as a very fine less soluble crystalline form within the polymer. We have also discovered that this second reaction leads to greater interaction between the polymer and calcium phosphate substantially increasing the material rigidity. A further advantage of the re - precipitated phosphate is that it can neutralise the acidic degradation products of poly(esters) preventing potential adverse inflammatory reactions which are a well documented problem with medical devices produced with these polymers. The calcium phosphate addition also provides us with an alternative means to control degradation rate but we anticipate they will additionally improve cellular responses. There is a massive range of possible injectable poly(esters) but to reduce the number of samples that need to be studied to optimise new formulations we have previously used experimental (factorial) designs that provide us with understanding as to which variable factors most affect rate and final level of polymer crosslinking, rigidity and degradation and drug release rates. In this new study we will extend these methods to interpret how these properties are altered through reactive filler addition but also determine mechanical strength. Key in our new investigations however, will be improving our understanding of what chemical changes illicit enhanced cellular responses. Our ultimate aim will be to find an optimal formulation that will then be assessed in vivo.