3D-printed biomaterial-based scaffolds loaded with zoledronic acid functionalised ceramic microparticles for sustained release.

Bisphosphonates (BPs), such as zoledronic acid (ZLD), are widely utilised as alternative treatment in bone-loss related disorders, including bone metastasis. Systemic administration of zoledronic acid (ZLD) is associated with significant adverse effects, most notably osteonecrosis of the jaw (ONJ). Recent advancements have focused on combining functionalising ceramics with BPs to enhance their physicochemical properties and bioactivity, while simultaneously contributing to both bone repair and cancer treatment. 3D printed scaffolds, as advanced drug delivery systems (DDSs), offer personalised solutions that ensure localised drug release while mitigating systemic side effects. This study aimed to develop precise manufacturing workflows of ZLD-functionalised hydroxyapatite (HA) microspheres, subsequently incorporating them into polycaprolactone (PCL)-based 3D printed scaffolds for sustained release. HA-ZLD (HZ) composites were formulated at HA:ZLD ratios of 1:1 and 3:1, followed by oven- or freeze-drying. Produced composites where characterised in terms of thermal stability, surface morphology, and bond formations. Thereafter, a single step melt extrusion 3D printing (3DP) technique was implemented for the fabrication of PCL scaffolds containing HZ (10% w/w) composites and the printing parameters were optimised to ensure scaffold structural integrity. Thermal analysis confirmed uniform HZ dispersion into the polymeric composite blends, while mechanical testing revealed ZLD's critical role on increasing brittleness and reducing ductility of the scaffolds. Dissolution studies demonstrated that scaffolds exhibited limited drug release over a two-week period, indicating PCL's role in modulating drug diffusion. Overall, the developed fabrication process for ZLD-loaded 3D-printed scaffolds was deemed reliable, highlighting its promising approach for sustained drug delivery.