Abstract
Ceramics such as hydroxyapatite are routinely used in fracture repair. However, their effects could be significantly improved as its bioavailability is incredibly poor (issues including low solubility, anionic charge, tendency to agglomerate). Nanoscale hydroxyapatite are gaining much interest, demonstrating increased effectiveness when compared to their micro-sized counterpart. In this study, we have developed a bioactive cargo–polymer-based system that allowed for the sustained, localised non-viral delivery of hydroxyapatite nanoparticles using an amphipathic peptide as a capping agent. The nanoparticles were delivered from a polycaprolactone nanofibre reinforced novel Alg-co-PNIPAAm thermoresponsive hydrogel. The bioactive cargo–polymer-based system was characterised in terms of its physiochemical properties, in vitro properties and in vivo performance using a subcutaneous mouse model. From this study, we have demonstrated that osteogenesis and bone regeneration were significantly increased when our novel capping agent was used to limit the particle size distribution and optimised the physiochemical characteristics of nanoscale hydroxyapatite (i.e. reducing risk of agglomeration and increasing its bioavailability). Additionally, the dual functionality of the thermoresponsive hydrogel as a scaffold for bone regeneration and as a vehicle for the sustained, local delivery of hydroxyapatite nanoparticles over an extended period was successfully demonstrated.