Microalgae have increasingly come into focus as multifunctional biological resources, offering significant promise in regenerative medicine and tissue engineering (Kapoor et al., 2024, Payares et al., 2023, Siddiqui et al., 2024). These unicellular, photosynthetic organisms—abundant across both marine and freshwater ecosystems—exhibit unique biochemical and physiological traits that align well with the demands of biomedical innovation (Aswathi Mohan et al., 2022, Garcia-Garcia et al., 2024, Moreira et al., 2023, Ragni et al., 2018). Their rapid proliferation, environmental adaptability, and capacity to biosynthesize a broad spectrum of compounds—including polysaccharides, pigments, proteins, and minerals—have sparked growing interest in their application to next-generation biomaterials (Kapoor et al., 2024, Moreira et al., 2023, Zhang et al., 2019). As the field shifts toward more sustainable and efficient therapeutic platforms, microalgae present a biologically complex yet scalable solution that supports both innovation and clinical feasibility (Aswathi Mohan et al., 2022, Zhang et al., 2019, Ortega et al., 2023, Sun et al., 2024).

The move toward bioactive, environmentally responsible materials is largely driven by the shortcomings of conventional scaffolds. Materials derived from synthetic polymers or animal tissues often suffer from drawbacks such as immunogenicity, limited biocompatibility, ethical concerns, and suboptimal biological performance (Mehta, 2009, Rastogi and Kandasubramanian, 2019, Tupe et al., 2024). These issues have pushed researchers to investigate alternative sources with intrinsic therapeutic properties. In this context, microalgae offer a highly attractive option, combining natural biocompatibility with ecological sustainability and a capacity to generate bioactive molecules independent of animal-derived inputs (Kapoor et al., 2024, Payares et al., 2023, Aswathi Mohan et al., 2022). This aligns well with current trends in biofabrication, which prioritize functional performance while reducing safety risks and ethical challenges.

A particularly notable feature of microalgae is their ability to carry out photosynthesis, which allows them to generate oxygen—an essential benefit in engineered tissues prone to hypoxia. In thicker or poorly vascularized constructs, oxygen diffusion is often inadequate, compromising cell survival and integration. When encapsulated in hydrogels or bioinks, photosynthetic species like Chlorella vulgaris and Euglena gracilis can continuously produce oxygen in situ, promoting improved cell viability, neovascularization, and overall regenerative outcomes (euglena co, 2022, Ishikawa et al., 2022; Lee et al., 2025b, Lee et al., 2025a; Wang et al., 2022). In addition to oxygen generation, microalgae secrete a variety of bioactive metabolites—such as sulfated polysaccharides (e.g., fucoidan and alginate), carotenoids, β-glucans, peptides, and polyphenols—that have demonstrated roles in enhancing osteogenesis, supporting extracellular matrix mineralization, and modulating immune responses (Changotade et al., 2008, Ishimi et al., 2006, Kim and Park, 2022).

Microalgae have gained growing attention as living bioactive components in 3D bioprinting, offering multifunctional benefits for tissue regeneration. Their role spans from oxygen-generating scaffolds to sources of bioactive metabolites for osteogenesis and wound healing. A visual summary of these interrelated functionalities is presented in Fig. 1, highlighting key processes such as oxygen diffusion, antioxidant release, and bone matrix mineralization.

Recent advances in biofabrication have also expanded the role of microalgae from passive inclusions to active, engineered components of living constructs. Their integration into hydrogel-based bioinks has enabled the development of photosynthetically active, structured scaffolds with improved mechanical integrity and biological function. Microalgal strains such as E. gracilis, Spirulina, and Chlorella have shown compatibility with mammalian cell cultures and suitability for incorporation into 3D-printed architectures (Bin Abu Sofian et al., 2024, Kumar et al., 2021, Mirzapour-Kouhdasht et al., 2024, Vazquez-Martel et al., 2024). Researchers have begun designing multi-layered, zone-specific scaffolds that capitalize on microalgae’s dual roles—oxygen production and biochemical support—while their extracellular polymeric substances contribute to scaffold stability and sustained bioactivity (Balasubramanian et al., 2021, Oh et al., 2024, Wangpraseurt et al., 2022; Zhang et al., 2024a, Zhang et al., 2024b).