Microalgae-based living biomaterials for immunoengineering: from biological functions to therapeutic systems

The immune system plays a central role in maintaining physiological homeostasis and protecting against infections, cancer, and inflammatory diseases. Immunoengineering, broadly defined as the strategic design and manipulation of immune responses, has emerged as an interdisciplinary field integrating immunology, materials science, and biomedical engineering, enabling substantial advances in the precise modulation of immune function. However, conventional immunomodulatory materials-such as synthetic polymers, nanoparticles, and biologically derived matrices-generally function as passive platforms, with limited capacity to dynamically adapt to complex and evolving pathological microenvironments. To address these limitations, living biomaterials have emerged as a transformative paradigm. Among them, microalgae represent a particularly promising and versatile platform, owing to their intrinsic photosynthetic oxygen-generating capability, diverse production of bioactive metabolites, favorable biocompatibility, scalability, and amenability to genetic engineering. Microalgae can alleviate hypoxia, modulate inflammatory signaling pathways, and produce antioxidant and anti-inflammatory metabolites as well as extracellular vesicles, thereby enabling cross-kingdom communication with host systems. Recent advances have further demonstrated their integration with polymers, nanomaterials, and microbial systems to construct multifunctional biohybrid platforms for active and adaptive immune modulation. Despite rapid progress, the field remains fragmented, and a systematic framework for translating microalgae-based living biomaterials into immunomodulatory therapies is still lacking. This review provides a comprehensive overview of microalgae-derived living biomaterials for immunoengineering, including their fundamental biological characteristics and mechanisms of immune regulation, key engineering strategies (such as encapsulation, biohybridization, and genetic engineering), and emerging therapeutic applications. In addition, current challenges and future perspectives for clinical translation are critically discussed.