Synthesis and characterization of biodegradable thermosensitive neutral and acidic poly(organophosphazene) gels bearing carboxylic acid group

A novel approach to provide, thermally sensitive neutral solutions based on chitosan/polyol salt combinations is described. These formulations possess a physiological pH and can be held liquid below room temperature for encapsulating living cells and therapeutic proteins; they form monolithic gels at body temperature. When injected in vivo the liquid formulations turn into gel implants in situ. This system was used successfully to deliver biologically active growth factors in vivo as well as an encapsulating matrix for living chondrocytes for tissue engineering applications. This study reports for the first time the use of polymer/polyol salt aqueous solutions as gelling systems, suggesting the discovery of a prototype for a new family of thermosetting gels highly compatible with biological compounds.

There are many potential applications of 'intelligent' aqueous polymer systems in medicine, biotechnology, industry and in environmental problems. Many of these polymer systems undergo reversible phase transitions--for example, abrupt changes in volume--in response to external stimuli such as temperature, pH or the nature of the solvent. Most of the polymers studied previously are responsive to only one kind of stimulus. But for some applications, independent responsiveness to several factors, such as temperature and pH, may be required. Here we describe a polymer that undergoes marked solubility changes in water in response to temperature and/or pH changes. The polymer is prepared by grafting temperature-sensitive side chains onto a pH-sensitive backbone. We also find that block copolymers, in which the temperature- and pH-sensitive units alternate along the chain, show similar behaviour.