Composite Liquid Marble Templated Millimetric Capsule With Tunable Rigidity, Porosity, and Thermal Reconfigurability Toward 3D Cell Culture

Abstract

ABSTRACT The extensive reliance on animal models in biomedical research motivates the development of advanced in vitro systems that recapitulate physiological complexity while minimizing animal use. Large cellular spheroids can mimic native tissue architecture; however, scalable fabrication of spheroids exceeding millimeter dimensions remains challenging. Here, we introduce a rigid porous capsule (RPC) in millimeter scale, a mechanically robust yet highly permeable platform that imposes external geometric confinement to enable cell–cell aggregation and three‐dimensional proliferation. The RPC is fabricated by thermally processing LMs composed of a binary mixture of superhydrophobic particles: meltable poly(octadecyl acrylate) (PODAc) microparticles and non‐meltable bovine serum albumin (BSA) nanoparticles. Selective melting of PODAc induces a transformation of the initially fragile, porous LM shell into a rigid and macroporous architecture (pore size in µm scale). By modulating the binary mixture composition, the shell stiffness and porosity are precisely tuned to balance mechanical stability with efficient nutrient transport. The resulting RPCs retain a highly spherical geometry and support 3D cell culture for at least 14 days, enabling the formation of viable, scaffold‐free spheroids on a millimetric scale. This RPC establishes a physiologically relevant system for advanced tissue modeling and drug screening.