Living Biomaterials: Fabrication Strategies and Biomedical Applications

Natural or bioengineered living organisms (including mammalian cells, bacteria, microalgaes, yeast, viruses, plant cells, and the multiple organism community) possess many intrinsic or artificial superiorities than the synthesized and inert biomaterials for application in many fields, especially biomedical applications. By leveraging the inherent or artificial therapeutic competences (e.g., disease chemotaxis, drugs production, intelligent delivery, immune activation and metabolic regulation), these living organisms have been developed as critical therapeutic formulations for biomedical applications to solve unmet medical needs. These living organisms are more intelligent, more easily available, more highly active, and more strongly curative than conventional inert formulations, such as inorganic nanocarriers, metal–organic chelating networks, polymeric nanovesicles and biomembrane biohybrids, etc. Nevertheless, nonspecific in vivo circulation, the diseased microenvironment-triggered inactivation, uncontrolled proliferation or colonization, unexpected side effects, and unsatisfactory therapeutic effect severely restricted their further research development and clinical approval. Living biomaterials, fabricated by integrating tailored functional materials with natural or bioengineered living organisms by chemical conjugation, physical assembly, and biological engineering strategies as well as advanced construction techniques, are rapidly developed to preserve or augment bioactivity and therapeutic properties of living organisms and even control their behaviors, decrease their biotoxicity, and impart them with new biofunctionalities, like stress resistance, bioactivity maintenance, safe trafficking, controllable proliferation and colonization, and evolved metabolism properties. These acquired capacities are especially beneficial to improve therapeutic potency and compliance, solve significant therapeutic restrictions, avoid biosafety questions, enhance therapeutic performances, and extend the boundaries of the fabricated living biomaterials on science research and practical biomedical applications. Additionally, the introduction of biocompatible and instructive functional materials, such as inorganic materials, synthetic polymers and polypeptides, functional proteins and enzymes, as well as biological component materials, can also promote the interaction of living biomaterials with the living body and provide feedback to further adapt the biofunctions of living organisms.

In this Account, we present a brief overview of recent advances of living biomaterials in their fabrication strategies and biomedical applications, embracing living organism species as well as living organism communities. We introduce the typical and practicable methods and techniques for fabrication of living biomaterials, mainly including chemical conjugation, physical assembly, biological editing, and metabolic engineering. On the basis of these fabrication strategies, the representative examples of living biomaterials for disease therapy (including tumors, metabolic disorders, metal poisoning, inflammatory bowel diseases (IBD), organ failure, etc.) are summarized and discussed. Finally, we highlight the main drawbacks, current challenges, potential solutions, and future research opportunities of living biomaterial fabrication and potential biomedical applications.