Pharmaceutical polymer-based hydrogels for 3D bioprinted drug delivery and tissue engineering applications

Abstract

3D bioprinting enables the layer-by-layer fabrication of living tissue constructs and supports patient-specific customization. This technology holds strong promises for regenerative medicine and drug discovery. However, its broader translation remains limited by material variability, safety considerations, cost constraints and regulatory requirements. This study investigates the use of safe, affordable and regulatory-compliant pharmaceutical polymers as biomaterials for 3D bioprinting. It specifically focuses on hydrogels formulated from Starch 1500®, maltodextrin and sodium alginate. The objective is to assess their potential applications in skin tissue engineering and oral drug delivery through semisolid extrusion-based 3D bioprinting techniques. Ionic crosslinking of the hydrogel was confirmed by FTIR analysis. The hydrogel exhibited a viscosity of 1.56 × 106 mPa·s, supporting semisolid extrusion bioprinting and excellent printability under ambient conditions. It enabled the fabrication of multilayer scaffolds with uniform filaments, well-defined square pore geometry and good shape fidelity. Rheological analysis showed shear-thinning behavior under applied stress, 87% thixotropic recovery and predominantly solid-like behavior at rest. Cast films showed a tensile strength of 33.9 MPa with limited extensibility, whereas lyophilized scaffolds exhibited high porosity and an average pore size of 39.2 μm. The 3D-printed scaffolds swollen upto 72% within 24 h and showed the onset of degradation after 2 weeks. Biological evaluation confirmed non-cytotoxicity, with more than 70% cell viability in skin-relevant L929 and HaCaT cells and good hemocompatibility, indicated by 5.0% hemolysis. Confocal microscopy further showed cell growth on the crosslinked hydrogel, supporting their potential for skin tissue engineering. Glimepiride-loaded bioinks were successfully formulated into chewable tablets for drug delivery, which exhibited acceptable physical properties. The tablets demonstrated excellent content uniformity (100.4%), while dissolution results showed sustained-release profiles over a time period of four hours. Our research indicates that pharmaceutical-grade polymer-based hydrogels are promising candidates for skin tissue engineering and drug delivery through 3D bioprinting. The findings of this study underscore the potential of these formulations to advance bioprinting technologies and related applications.