RESOURCES

Abstract
Abstract We have used three dimensional (3D) extrusion printing to manufacture a multi-active solid dosage form or so called polypill. This contains five compartmentalised drugs with two independently controlled and well-defined release profiles. This polypill demonstrates that complex medication regimes can be combined in a single personalised tablet. This could potentially improve adherence for those patients currently taking many separate tablets and also allow ready tailoring of a particular drug combination/drug release for the needs of an individual. The polypill here represents a cardiovascular treatment regime with the incorporation of an immediate release compartment with aspirin and hydrochlorothiazide and three sustained release compartments containing pravastatin, atenolol, and ramipril. X-ray powder diffraction (XRPD) and Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) were used to assess drug-excipient interaction. The printed polypills were evaluated for drug release using {USP} dissolution testing. We found that the polypill showed the intended immediate and sustained release profiles based upon the active/excipient ratio used.

Abstract
Bone defects arising due to trauma, disease, or surgical resections continue to constitute serious clinical challenges, demanding more advanced and customizable solutions that not only ensure structural stability, but also replicate the anisotropy and biomimetic complexity of the native bone tissue. In this context, we present a solution that is based on 3D printed scaffolds made of gellan gum (GG) and cellulose nanofibrils (CNFs), reinforced with electrospun chitosan/polyethylene oxide nanofibers (NFs). First, we optimized the base ink by selecting the proper GG/CNFs ratio as 3/1 after evaluating its rheological properties, printability, and scaffold morphology. Next, various concentrations of NFs (0.5, 1, 2, and 4 wt%) were added to the base ink, and the resulting formulations were again evaluated in terms of rheology and printability, while the subsequent printed scaffolds were investigated by scanning electron microscopy and micro-computed tomography, showing a well-organized internal architecture with interconnected pores and improved volumetric fidelity, especially for 2 % NFs addition (GCN-2.0), which recorded the highest total porosity (90.7 %). Structural characterization confirmed the successful integration of NFs within the polymeric matrix, while nanomechanical indentation revealed an increase in storage modulus (72.5 kPa for GCN-2.0) compared to the control (47.5 kPa) and also mechanical anisotropy due to filament orientation and NFs alignment within the printed structures. In vitro swelling and degradation studies showed the highest increase in water uptake capacity and long-term stability (up to 12 weeks) for GCN-2.0, while biological evaluation demonstrated good cytocompatibility with MG-63 cells for all samples and increased mineralization in the scaffolds with higher NFs content. Overall, the results indicate that 2 % NFs reinforcement constitutes the ideal balance between printability, nanomechanical properties, and biological response, indicating a great potential for this hybrid formulation to be used successfully in bone tissue engineering.