Liquefied Multilayered Microcapsules Encapsulating Light‐Responsive Polymersomes for On‐Demand Temporally Controlled Enzyme‐Mediated Cell Delivery

Creating platforms that support long‐term cell culture under controlled conditions while preserving biological activity remains a major challenge. Liquefied microcapsules surrounded by a semi‐permeable multilayered membrane prepared by the electrostatic‐driven layer‐by‐layer (LbL) assembly of polyelectrolytes provide protective environments for cell encapsulation while preserving the mass transport required to sustain cell viability. However, strategies to enable on‐demand capsule degradation and controlled release of encapsulated contents are limited. Herein, we report the design and development of alginate‐based multilayered microcapsules encapsulating primary human adipose‐derived mesenchymal stem cells and light‐responsive biocompatible polymersomes loaded with alginate lyase. Upon light irradiation, polymersomes release the encapsulated enzyme into the surrounding medium, where it retains its catalytic activity, triggering the degradation of the microcapsule's core in a temporal manner and, ultimately, cell release. The critical role of the LbL‐driven multilayered membrane shell in modulating the release profile is demonstrated, together with the biocompatibility of the compartmentalized system. This work proposes an unprecedented on‐demand light‐triggered cell delivery platform that integrates the stimuli‐responsiveness of polymersomes with the protective nature, versatility, and structural advantages imparted by multilayered microcapsules, paving the way for the development of advanced (multi)compartmentalized stimuli‐responsive systems for controlled drug/therapeutics/cell delivery, tissue engineering and regenerative medicine.