Pierceable, Storable, and Manipulable Liquid Capsules for Precise Monitoring and Efficient Cargo Transport in Biotechnological Advances

Abstract

Soft liquified capsules are explored for various biotechnological applications owing to their versatility and protective nature. However, it is challenging to assess and control their internal environment post‐production without compromising their structural integrity. This study explores liquid capsules with shells created from gelatin modified with hydroxypyridinone groups and coordinated with iron ions to enable access to and control over their internal content. Using glycerol as a cryoprotectant prevents ice crystal formation in gelatin‐derived hydrogel pores during storage at −20 °C. The hygroscopic properties provided by glycerol effectively preserve the structural and self‐healing features of the shell over time, supporting large‐scale production of off‐the‐shelf containers. As a proof‐of‐concept, the ability to manipulate the internal content, and real‐time analysis of internal pH, oxygen, and protein levels is shown. The nature of these capsules allows them to closely emulate the elasticity and self‐healing of natural cell membranes, enabling in situ modulation of the internal content without compromising the capsule structural integrity. These findings support the development of universal incubator units for in vitro studies, advancing bioreactors, sensors, and frameworks crucial for bioengineering microtissues across diverse applications.