Chitosan-based hydrogels containing enzyme alkaline phosphatase / Hydrożele chitozanowe zawierające enzym alkaliczną fosfatazę

The present inventors have developed new thermogelling systems by adding enzyme alkaline phosphatase solution to thermosensitive chitosan/betaglycerophosphate solutions. This approach surprisingly was found to solve the problems associated with the existing systems such as insufficient and/or slow gelation at body temperature and the lack of a mineral phase within hydrogels with associated lack of bioactivity. It was surprisingly found that the resulting thermogelling system has improved gel formation characteristics, especially a shorter gelation time. Gelation of different chitosan preparations can be accelerated to a speed more suitable from a clinical point of view. Furthermore, it was observed that the present invention can yield satisfactory gelation properties with a wider range of chitosan preparations, for instance in terms of deacetylation degrees.

The presence of enzyme alkaline phosphatase was furthermore found to enhance formation of CaP mineral inside the hydrogels. For bone contact applications, the presence of a ceramic phase based on calcium phosphate (CaP) leads to a number of advantages, including increased bioactivity (formation of chemical bonds with surrounding bone after implantation) and affinity for biologically active proteins such as growth factors, which stimulate the natural healing processes of surrounding bone. Since stiffer and rougher surfaces are known to promote differentiation of cells towards the osteoblastic phenotype, mineralisation is expected to make chitosan more bone-friendly.

Biomateriały, chitozan, ALP, hydrożele, inżynieria tkankowa

The present invention thus provides new thermogelling systems, their use in methods of aesthetic and/or reconstructive intervention in a human or mammalian subject, as well as products for carrying out such methods. As gelation of different chitosan preparations can be accelerated to a speed more suitable from a clinical point of view, i.e. within 20 minutes, this method enables the application of a wider range of chitosan preparations with differing properties, such as DD. DD influences degradability, inflammatory response, and antibacterial properties. Therefore ALP addition is also interesting for companies developing chitosan hydrogels for non-bone related applications such as drug delivery. The simplicity of this method should be of interest to companies working on injectable materials for bone regeneration.

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