Biodegradable bone cement compositions based on acrylate and epoxide terminated poly(propylene fumarate) oligomers and calcium salt compositions

Abstract

The synthesis of biodegradable bone cement compositions is presented. These bone cement compositions can be applied as a putty-like mixture and harden to a strong material in a bone fracture. They degrade from the site of application to allow the ingrowth of new bone for complete healing of the bone fracture. The bone cement is composed of a solid particulate phase dispersed in an initially liquid polymeric phase, which can be hardened by cross-linking. The polymeric phase is a low-molecular-weight liquid poly(propylene fumarate) (PPF) containing double bonds available for cross-linking. The solid particulate phase consists of calcium carbonate and tricalcium phosphate. PPF oligomers of Mw = 1800 and Mn = 750 were prepared from the condensation of non-volatile bis(2-hydroxypropyl fumarate) and propylene-bis(hydrogen maleate) trimers. PPF terminated divinyl and diepoxide derivatives were obtained from the reactions between PPF diol and acryloyl chloride or epichlorhydrin, respectively. Putty-like cement compositions were prepared from a mixture of 30 wt% polymer phase containing benzoyl peroxide-dimethyl toluidine as polymerization catalyst and 70 wt% calcium salts. The divinyl and diepoxide terminated PPF oligomers provided a high strength composition of between 30 and 129 MPa which is suitable for bone cement applications. In vitro hydrolysis of the composites showed little weight loss with the compressive strength remaining above 20 MPa after 4 weeks in buffer solution. Compositions of the PPF oligomers cross-linked without calcium salts showed a gradual weight loss (10-65 wt% after 4 weeks) when placed in buffer solution followed by high water absorption (18-200 wt% after 4 weeks), with the epoxide terminated PPF being the least to degrade or absorb water.