Development of Highly Printable GelMA/Laponite Bioinks by a Rheology-Guided Design Strategy: Impact of the GelMA Synthetic Procedure

Gelatin methacryloyl (GelMA) is the most widely used biomaterial for extrusion-based bioprinting. However, its intrinsic rheological properties often require optimisation with rheological modifiers, such as the nanoclay Laponite (Lapo). Since the rheological behaviour of GelMA/Lapo hybrid bioinks depends on polymer–nanoclay interactions, the physicochemical and conformational properties of GelMA are expected to critically influence Lapo incorporation, the resulting rheological behaviour, and ultimately printability. Accordingly, this study combines formulation design with a systematic rheology-guided screening strategy. Two GelMA derivatives (GelMADP and GelMASP) obtained through different synthesis procedures, and characterised by distinct physicochemical and structural properties, were used to prepare GelMA/Lapo bioinks under physiologically relevant conditions. GelMASP enabled homogeneous incorporation of higher Lapo contents than GelMADP, expanding the formulation space and allowing the development of hybrid inks with improved rheological properties. A sequential rheological roadmap integrating oscillation temperature-ramp, flow-sweep, yield stress, and elastic recovery analyses was then used to progressively screen the formulations and guide the selection of suitable processing conditions. Among the investigated formulations, SP20-3 (20% w/v GelMASP and 3% w/v Lapo) exhibited the most suitable rheological profile, combining favourable temperature-dependent gelation, pronounced shear-thinning behaviour, and rapid structural recovery, ultimately leading to high printing fidelity. These properties were largely retained also after high-density cell inclusion. Overall, these results identify the physicochemical and conformational properties of the starting GelMA as critical design parameters governing polymer–clay network organisation, rheological behaviour, and bioink printability, while highlighting the value of a systematic rheology-guided approach for formulation screening and optimisation.