Incorporation of chitosan-alginate complex into injectable calcium phosphate cement system as a bone graft material

Abstract

Calcium phosphate brushite type of cements have been used to replace bone graft materials because of their biocompatibility and other attractive features. Especially, injectability of cement allows easy handling of minimally invasive surgical techniques. New calcium phosphate cement (CPC) system, brushite based cement incorporated into polyelectrolyte complex, was developed in this study. Chitosan-alginate complex produced by an interaction between a cationic polymer (chitosan) and an anionic polymer (alginate) was loaded in the cement. This improved the functional properties and biocompatibility of the final cement. We optimized the liquid/solid (L/S) ratio of the cement components and investigated the compressive strength, setting time, pH change of CPC0 (with only citric acid) and CPC0.5, 1, and 1.5 (0.5, 1, and 1.5 v/v % chitosan-alginate complex in citric acid solution, respectively). The L/S ratio did not affect structural formation, while the addition of polymer complex showed new formation of macro-pores within CPC. However, a lower L/S ratio and higher amount of added polymer complex shortened the setting time and improved the compressive strength. The appropriate conditions for the injectable bone substitute were CPC1 with an L/S ratio of 0.45. To investigate the effect of the chitosan-alginate complex on CPC system in physiological conditions, CPC0 and CPC1 were implanted in a rabbit femoral head defect model for 1 and 3 months. Micro-computed tomography revealed improved bone formation in CPC1 compared to CPC0 3 months after implantation. Histological analysis revealed newly formed bone tissues around the peripheral sides of CPC0 and CPC1. The results indicate the potential value of the CPC system containing polymer complex as an injectable bone substitute. The study of the CPC-polymer complex system incorporating drugs or cells can be further developed into a controlled release system for faster bone regeneration.