Chitosan-Based Hydrogels Embedded with Hyaluronic Acid Complex Nanoparticles for Controlled Delivery of Bone Morphogenetic Protein-2

Chitosan(CH)-poly(dioxanone) (CH-PDO) copolymers containing varied amounts of PDO and having free amino groups at their CH backbone were synthesized using a group protection method. The selected CH-PDO with soluble characteristics in aqueous media was used together with hyaluronic acid (HA) to prepare HA/CH-PDO polyelectrolyte complex nanoparticles (NPs) via an ionotropic gelation technique, and such a type of HA/CH-PDO NPs was employed as a carrier for delivering bone morphogenetic protein-2 (BMP-2). The optimal BMP-2-encapsulated HA/CH-PDO NPs with high encapsulation efficiency were embedded into CH/glycerophosphate composite solutions to form different hydrogels in order to achieve long-term BMP-2 release. The formulated gels were found to be injectable at room temperature and had its thermosensitive phase transition near physiological temperature and pH. They also showed abilities to administer the release of BMP-2 in approximately linear manners for a few weeks while effectively preserving the bioactivity of the encapsulated BMP-2. In view of their fully biocompatible and biodegradable components, the presently developed gel systems have promising potential for translation to the clinic use in bone repair and regeneration where the sustained and controlled stimuli from active signaling molecules and the stable biomechanical framework for housing the recruited cells are often concurrently needed.