Bioenzymatic single-cell microencapsulation for enhanced stem Cell therapy.

Cell therapy has achieved a critical breakthrough through single-cell microgel technology. This miniaturized encapsulation platform enables precise microenvironment recapitulation, efficient targeted delivery, and tunable pericellular matrix control. Nevertheless, prevailing microfluidic and surface chemical engineering methodologies confront fundamental challenges in preserving cell viability and functionality. Here, we establish a simple and bioenzymatic strategy for fabricating single-cell microgels, using microbial transglutaminase adsorption. This surfactant- and oil-free approach, without surface modification, permits universal, high-viability encapsulation of diverse cell types and biomaterials. We achieve 100 % encapsulation efficiency and robust mechanical protection. Therapeutic efficacy was assessed in myocardial infarction (MI) and pulmonary fibrosis (PF) models. In MI, microgel-encapsulated MSCs (MSC SCMs) significantly improved in vivo retention and survival, exhibiting superior tissue regeneration and cardiac function. In bleomycin-induced PF, TNF-α-loaded MSC SCMs potentiated MMP-13 secretion, achieving enhanced respiratory function and attenuated fibrotic lesions. This robust and universally applicable platform thus for advanced cell therapies, overcomes limitations in encapsulation while demonstrating potent therapeutic efficacy across disease models.