Strength in diversity: unlocking the full potential of engineered living materials with multistrain collaboration

Bottom-up approaches to engineered living materials: Challenges and future directions

At the intersection of synthetic biology and materials science, engineered living materials (ELMs) exhibit unprecedented potential. Possessing unique "living" attributes, ELMs represent a significant paradigm shift in material design, showcasing self-organization, self-repair, adaptability, and evolvability, surpassing conventional synthetic materials. This review focuses on reviewing the applications of ELMs derived from bacteria, fungi, and plants in environmental remediation, eco-friendly architecture, and sustainable energy. The review provides a comprehensive overview of the latest research progress and emerging design strategies for ELMs in various application fields from the perspectives of synthetic biology and materials science. In addition, the review provides valuable references for the design of novel ELMs, extending the potential applications of future ELMs. The investigation into the synergistic application possibilities amongst different species of ELMs offers beneficial reference information for researchers and practitioners in this field. Finally, future trends and development challenges of synthetic biology for ELMs in the coming years are discussed in detail.

Engineered living materials (ELMs) leverage the integrative advantages of materials science and synthetic biology for advanced functionalities. Predicting and controlling cellular behavior are essential for designing and building ELMs, requiring a fundamental understanding of the growth dynamics of encapsulated cells. Here, we interrogate the interference of constrained growth with the engineered functionalities and cellular physiology of cyanobacteria and unveil the dynamic interaction between cell growth and spatial confinements within photosynthetic ELMs. We observed that engineered cyanobacteria within ELMs exhibited compromised performances in growth, uptake of nonutilizable substrate, and synthesis of customized products, while ELMs could protect encapsulated cells from external stresses. Besides commonly accepted external influences, we identified abnormally high levels of reactive oxygen species and impaired oxygen photosynthesis inside the cells encapsulated in the ELMs. Finally, we illustrated the dynamics of cell growth within the confined spaces enveloped by the material matrices, forming clustered cell aggregates and compressed growth bubbles until the spatial limits. Our study provides a fundamental yet often overlooked connection between cellular behavior and spatial confinement, consolidating the foundation for advanced ELM innovations.

Engineered living materials (ELMs) design: From function allocation to dynamic behavior modulation

Engineered living materials (ELMs) at the multicelluar level represent an innovation that promises programmable properties for biomedical, environmental, and consumer applications. However, the rational tuning of the mechanical properties of such ELMs from first principles remains a challenge. Here we use synthetic cell-cell adhesins to systematically characterize how rheological and viscoelastic properties of multicellular materials made from living bacteria can be tuned via adhesin strength, cell size and shape, and adhesion logic. We confirmed that the previous results obtained for non-living materials also apply to bacterial ELMs. Additionally, the incorporation of synthetic adhesins, combined with the adaptability of bacterial cells in modifying various cellular parameters, now enables novel and precise control over material properties. Furthermore, we demonstrate that rheology is a powerful tool for actively shaping the microscopic structure of ELMs, enabling control over cell aggregation and particle rearrangement, a key feature for complex material design. These results deepen our understanding of tuning the viscoelastic properties and fine structure of ELMs for applications like bioprinting and microbial consortia design including natural systems.

The integration of functional synthetic materials and living biological entities has emerged as a new and powerful approach to create adaptive and functional structures with unprecedented performance and functionalities, and such hybrid structures are also called engineered living materials (ELMs). ELMs have the potential to realize many highly-desired properties, which are usually only found in biological systems, such as self-powered, self-healing, biosignal-responsive, and self-sustainable. Motivated by that, in recent years, researchers have started to explore the use of ELMs in many areas, among them, sensing and actuation is the area that has the most progress. In this short review, we briefly reviewed the important recent development in ELMs-based sensors and actuators, with a focus on their materials and structural design, new fabrication technologies, and bio-related applications. Current challenges and future directions in this field are also identified to help with future development in this emerging interdisciplinary field.

Vast potential exists for the development of novel, engineered platforms that manipulate biology for the production of programmed advanced materials. Such systems would possess the autonomous, adaptive, and self-healing characteristics of living organisms, but would be engineered with the goal of assembling bulk materials with designer physicochemical or mechanical properties, across multiple length scales. Early efforts toward such engineered living materials (ELMs) are reviewed here, with an emphasis on engineered bacterial systems, living composite materials which integrate inorganic components, successful examples of large-scale implementation, and production methods. In addition, a conceptual exploration of the fundamental criteria of ELM technology and its future challenges is presented. Cradled within the rich intersection of synthetic biology and self-assembling materials, the development of ELM technologies allows the power of biology to be leveraged to grow complex structures and objects using a palette of bio-nanomaterials.

Give Life to a Glue

Fungal fermentation offers a promising approach for the development of engineered living materials (ELMs). The design of the substrate materials to support and enhance fungal growth in both 2D and 3D is essential to realize this potential. We evaluated the mycelium of seven edible mushroom-forming fungi for growth vigor as a function of various abiotic factors. Growth assays using standard malt agar, with varying concentrations of carbohydrates and proteins, revealed that the radial expansion of the fungal is affected by the carbohydrate concentration, showing a maximum expansion rate at mid-low concentrations and a diminishing expansion rate at higher concentrations. In contrast, higher carbohydrate concentrations increased mycelium density. Different plant-based proteins also significantly influenced growth vigor, i.e. the mycelium's thickness and expansion rate. Beyond chemical substrate conditions, we modified the substrate viscoelasticity by increasing agar concentration, which resulted in higher growth proliferation. This was further confirmed using non-standard gelling agents such as guar gum, corn starch, κ-carrageenan, and bacterial cellulose. In a final step to enhance growth for practical applications, we foamed an optimized substrate material for 3D growth, achieving successful growth throughout the entire matrix. This work provides a framework to aid the selection of edible substrate materials for fungal growth, i.e. the design of engineered living materials.

The purpose of this overview was to make a broad inventory of investigational drugs for medicinal cancer treatment and, specifically, to indicate the evidence of clinical efficacy. Information was retrieved from electronic database searches in Medline and CANCERLIT and relevant published reviews. As the most recent findings are first reported as conference abstracts, an important basis for identification of new drugs and clinical results was a hand search of 13,392 abstracts from five major recent cancer conferences. A total of 209 investigational approaches or drugs were identified and classified into one of eight groups according to proposed mechanism of action. For 28 drugs/approaches survival data were available from randomized controlled trials. Statistically significant benefit was observed for only 12. In earlier phases no or modest anticancer activity was reported. It is speculated that the expanding knowledge in tumour biology might not easily translate into new substantially better anticancer drugs.

Synthetic Biology (SynBio) has emerged as the fastest-developing technology in human history, rapidly transforming industries by enabling novel biological system designs. This paper examines SynBio’s influence on architecture and construction, focusing on the evolution from Engineered Living Materials (ELMs) to Programmable Living Materials (PLMs). This paper is organized into four sections. The first introduces the field of SynBio and its initial impact on architectural design. The second section highlights contemporary ELM biomaterials projects and presents a taxonomy of emerging biomaterials in architecture. In the third section, we discuss a design proposal focused on bioplastics for small-scale, bio-grown habitats optimizing tension and elasticity. The final section explores PLMs, addressing the challenge of developing biostructures that transition seamlessly from nanoscale to macroscale while maintaining dynamic growth and function, as seen in large-scale living organisms. Speculative projects include self-lifting bio-membranes, 3D bioplastic structures, and spider silk infrastructures in a future of programmable materials.

Utilizing various materials is fundamental for the production of physical objects. However, processing raw materials during production often leads to complex transformations that hinder the recyclability of modern high‐performance materials. These materials possess increased durability and resilience, challenging their decomposition and limiting their potential for recycling and reuse. In contrast, living Nature manages material utilization without such complications. The emerging discipline of Engineered Living Materials (ELMs) shifts the focus to self‐repairing, self‐supporting growing materials, emphasizing overall sustainability. To effectively address the challenges associated with high‐performance materials, the design process must incorporate considerations of recycling and decomposition from the outset. Environmental challenges associated with material utilization can be addressed by reevaluating material design and prioritizing recycling, decomposition, and embracing Nature's “good enough” principle. The transition toward sustainable resource management requires substantial investment in scientific research that explores the mechanisms by which life sustains itself using solely local resources. Biomimetics and ELMs offer valuable insights, but a deeper understanding of how Nature efficiently utilizes resources is crucial. The integration of engineering advantages not identified in Nature, such as product sub‐unit reuse, can complement these efforts. Paving the way toward a sustainable future requires a comprehensive approach rooted in biological evolution and innovative scientific research.

This article suggests a framework for modelling a production system architecture in the early phases of product development. The challenge in these phases is that the products to be produced are not completely defined and yet decisions need to be made early in the process on what investments are needed and appropriate to enable determination of obtainable product quality. In order to meet this challenge, it is suggested that a visual modelling framework be adopted that clarifies which product and production features are known at a specific time of the project and which features will be worked on – leading to an improved basis for prioritizing activities in the project. Requirements for the contents of the framework are presented, and literature on production and system models is reviewed. The production system architecture modelling framework is founded on methods and approaches in literature and adjusted to fit the modelling requirements of a production system architecture at an early phase of development. The production system architecture models capture and describe the structure, capabilities and expansions of the production system architecture under development. The production system architecture modelling framework is tested in a case study, and the results indicate that the modelling process facilitates identification of critical factors of the production system architecture, that the production system architecture models capture and describe the structure, capabilities and expansions of a production system architecture under development, and that the production system architecture models can facilitate dialogue on the production system architecture between heterogeneous stakeholder groups.

Functions deserve special attention in the design and differentiation of products in the early phases of product development. However, it has become apparent that there is no uniform understanding of a function. This contribution analyzes and deepens the understanding, formulation and modeling of functions in research and product development in the early phases of development with the approach of a Systematic Literature Review (SLR). In literature, a function is primarily described from the (established) developmental perspective, but rarely from an environmental or human-centered viewpoint. In the latter case, such a function understanding enables the specification of a customer and user-oriented system of objectives. Furthermore, a purposeful formulation of a function can create a mutual comprehension among product developers and increase transparency in the early phase of research and development. There is a consensus to formulate a function as a noun-verb combination. In addition, the literature study has led to the conclusion that the level of abstraction should be taken into account when formulating a function. The results show the need of further research on defining a function on different product levels (system-of-system in the environment, subsystem and component) as a coherence of an initiating event and the desired outcome.

Nitric oxide drives embryonic myogenesis in chicken through the upregulation of myogenic differentiation factors