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Volumetrically Printed Porous Hydrogels for Ultrasound-Enhanced Drug Delivery

par Siminska-Stanny, Julia ;Noirot, Isaline I.N;Li, Man;Marcotulli, Martina M.M;Nair, Malavika M.N;Carugo, Dario D.C;Stride, Eleanor E.S;Shavandi, Armin
Référence European Society for Biomaterials, European Society for Biomaterials, ESB
Publication Publié, 2026-09-10

Abstract de conférence

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Résumé :

Introduction Ultrasound (US) and cavitation-mediated drug delivery hold substantial promise for improving the therapeutic index of drugs including chemotherapeutics. However, optimization of acoustic parameters remains challenging because microbubble dynamics are highly sensitive to the mechanical and transport properties of the surrounding tissue microenvironment. Conventional mechanically homogeneous gel phantoms, fail to reproduce physiologically relevant transport limitations (~100–200 µm) and often undergo brittle fracture under cavitation, limiting their predictive value.Materials and MethodsVolumetric bioprinting was used to fabricate porous GelMA–PEGDA hydrogel constructs with digitally tunable pore and channel architectures. Porosity and perfusable vascular-like channels (1 mm diameter) were introduced as programmable design parameters, enabling control over pore size, orientation, and connectivity. Transport properties were evaluated under static and perfusion conditions using model solutes of varying size and charge, including fluorescent dextrans of defined molecular weight (Fig.). Mechanical properties were assessed by rheological measurements. Ultrasound-mediated cavitation experiments were performed under perfusion at acoustic pressures 1 to 5 MPa to evaluate structural stability and acoustic compatibility and resulting acoustic signals were processed in MATLAB.ResultsEngineered porosity enhanced both passive diffusion and perfusion-driven convection. Interconnected pore networks reduced the storage modulus from ~2000 Pa in bulk hydrogels to ~900–1000 Pa and increased effective solute penetration by more than twofold under flow (Fig.). In contrast, closed-pore architectures softened the matrix but did not significantly improve permeability. Transport remained strongly dependent on molecular properties: small cationic molecules diffused rapidly (~1.8 mm in 30 min), whereas larger or highly anionic species exhibited restricted penetration due to steric and electrostatic interactions. Comparisons with near-neutral fluorescent dextrans enabled separation of size- and charge-mediated transport effects.Under ultrasound exposure, porous constructs effectively transmitted acoustic energy and sustained stable cavitation at therapeutic pressures up to 3 MPa without structural failure, whereas bulk hydrogels exhibited crack-like damage. Structural damage in porous systems was observed only above 5 MPa (Fig.).Conclusion Volumetrically printed porous hydrogels provide a mechanically stable and transport-relevant platform integrating passive diffusion, convection, and ultrasound-driven delivery. By quantitatively linking architecture, mechanics, transport, and cavitation response, this system establishes a predictive framework for optimizing ultrasound-assisted drug delivery.AcknowledgementsThis study was supported by an Aspirant fellowship from the Fonds National de la Recherche Scientifique de Belgique (FNRS) (grant number 46599), 2022 awarded to Julia Stanny. Additional support to J.S. was provided by the SofinaBoël Fellowship, and the Fondation Philippe Wiener – Maurice Anspach.