Design principles for adaptive and evolving engineered living materials.

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

Programmable Materials.

With the rise of engineered living materials (ELMs) as innovative, sustainable and smart systems for diverse engineering and biological applications, global interest in advancing ELMs is on the rise. Graphene-based nanostructures can serve as effective tools to fabricate ELMs. By using graphene-based materials as building units and microorganisms as the designers of the endmaterials, next-generation ELMs can be engineered with the structural properties of graphene-based materials and the inherent properties of the microorganisms. However, some challenges need to be addressed to fully take advantage of graphene-based nanostructures for the design of next-generation ELMs. This work covers the latest advances in the fabrication and application of graphene-based ELMs. Fabrication strategies of graphene-based ELMs are first categorized, followed by a systematic investigation of the advantages and disadvantages within each category. Next, the potential applications of graphene-based ELMs are covered. Moreover, the challenges associated with fabrication of next-generation graphene-based ELMs are identified and discussed. Based on a comprehensive overview of the literature, the primary challenge limiting the integration of graphene-based nanostructures in ELMs is nanotoxicity arising from synthetic and structural parameters. Finally, we present possible design principles to potentially address these challenges.

Harnessing proteins for engineered living materials

Engineered living materials grown from programmable Aspergillus niger mycelial pellets.

Engineered living materials (ELMs) embed living cells in a biopolymer matrix to create materials with tailored functions. While bottom-up assembly of macroscopic ELMs with a de novo matrix would offer the greatest control over material properties, we lack the ability to genetically encode a protein matrix that leads to collective self-organization. Here we report growth of ELMs from Caulobacter crescentus cells that display and secrete a self-interacting protein. This protein formed a de novo matrix and assembled cells into centimeter-scale ELMs. Discovery of design and assembly principles allowed us to tune the composition, mechanical properties, and catalytic function of these ELMs. This work provides genetic tools, design and assembly rules, and a platform for growing ELMs with control over both matrix and cellular structure and function.

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.

Future advances in therapeutics demand the development of dynamic and intelligent living materials. The past static monofunctional materials shall be unable to meet the requirements of future medical development. Also, the demand for precision medicine has increased with the progressively developing human society. Therefore, engineered living materials (ELMs) are vitally important for biotherapeutic applications. These ELMs can be cells, microbes, biofilms, and spores, representing a new platform for treating intractable diseases. Synthetic biology plays a crucial role in the engineering of these living entities. Hence, in this review, the role of synthetic biology in designing and creating genetically engineered novel living materials, particularly bacteria, has been briefly summarized for diagnostic and targeted delivery. The main focus is to provide knowledge about the recent advances in engineered bacterial-based therapies, especially in the treatment of cancer, inflammatory bowel diseases, and infection. Microorganisms, particularly probiotics, have been engineered for synthetic living therapies. Furthermore, these programmable bacteria are designed to sense input signals and respond to disease-changing environments with multipronged therapeutic outputs. These ELMs will open a new path for the synthesis of regenerative medicines as they release therapeutics that provide in situ drug delivery with lower systemic effects. In last, the challenges being faced in this field and the future directions requiring breakthroughs have been discussed. Conclusively, the intent is to present the recent advances in research and biomedical applications of engineered bacteria-based therapies during the last 5 years, as a novel treatment for uncontrollable diseases.

Engineered living materials (ELMs) are an emerging class of materials that are synthesized and/or populated by living cells to achieve novel functionalities including self‐healing and sensing. Providing nutrients to living cells within an ELM over prolonged periods remains a major technical challenge that limits the service life of ELMs. Bone maintains living cells for decades by delivering nutrients through a network of nanoscale channels punctuated by microscale pores. Nutrient transfer in bone is enabled by mechanical loading experienced by the material during regular use. Herein, the geometric traits of the network of channels and pores that can be used in ELMs to allow mechanical loading to enable nutrient delivery to resident cell populations are identified in a manner seen in bone. Transport occurs when deformation in the microscale pore network exceeds the volume of the connecting channels. Computational models show that transport is enhanced at greater loading magnitudes and lower loading frequencies. The computational results are confirmed using experiments with microfluidic systems. In the findings, quantitative design principles are provided for channel‐pore networks capable of sustained delivery of nutrients to living cells within materials.

Recent advances in synthetic biology and materials science have given rise to a new form of materials, namely engineered living materials (ELMs), which are composed of living matter or cell communities embedded in self-regenerating matrices of their own or artificial scaffolds. Like natural materials such as bone, wood, and skin, ELMs, which possess the functional capabilities of living organisms, can grow, self-organize, and self-repair when needed. They also spontaneously perform programmed biological functions upon sensing external cues. Currently, ELMs show promise for green energy production, bioremediation, disease treatment, and fabricating advanced smart materials. This review first introduces the dynamic features of natural living systems and their potential for developing novel materials. We then summarize the recent research progress on living materials and emerging design strategies from both synthetic biology and materials science perspectives. Finally, we discuss the positive impacts of living materials on promoting sustainability and key future research directions.

The fusion of synthetic biology and materials science offers exciting opportunities to produce sustainable materials that can perform programmed biological functions such as sensing and responding or enhance material properties through biological means. Bacterial cellulose (BC) is a unique material for this challenge due to its high-performance material properties and ease of production from culturable microbes. Research in the past decade has focused on expanding the benefits and applications of BC through many approaches. Here, we explore how the current landscape of BC-based biomaterials is being shaped by progress in synthetic biology. As well as discussing how it can aid production of more BC and BC with tailored material properties, we place special emphasis on the potential of using BC for engineered living materials (ELMs); materials of a biological nature designed to carry out specific tasks. We also explore the role of 3D bioprinting being used for BC-based ELMs and highlight specific opportunities that this can bring. As synthetic biology continues to advance, it will drive further innovation in BC-based materials and ELMs, enabling many new applications that can help address problems in the modern world, in both biomedicine and many other application fields.

Filamentous fungi offer unique potential for engineered living materials (ELMs), enabling self‐assembling, adaptive, and sustainable biofabrication. However, the field lacks a systematic framework to classify fungal ELMs, as they vary in biological state (dead, dormant, or living), scaffold composition, and degree of engineering intervention. Here, a classification system is introduced to categorize fungal ELMs, enabling researchers to map existing studies and guide future development. The ability to form resilient 3D networks make filamentous fungi ideal for applications ranging from self‐healing composites to materials for bioremediation and real‐time sensing, as demonstrated in proof‐of‐concept applications. A roadmap for next‐generation fungal ELMs is outlined, including spatial–temporal control of fungal states, multispecies integration for enhanced complexity, and computational modeling for predictive design. Key challenges, such as contamination control, cell viability, and bio‐digital integration, are discussed alongside strategies for genetic engineering. Finally, ethical and environmental considerations are emphasized as crucial factors for the responsible scaling of fungal ELMs.

Encapsulation of microbes in natural or synthetic matricesis akey aspect of engineered living materials, although the influenceof such confinement on microbial behavior is poorly understood. Afew recent studies have shown that the spatial confinement and mechanicalproperties of the encapsulating material significantly influence microbialbehavior, including growth, metabolism, and gene expression. However,comparative studies within different bacterial species under identicalconfinement conditions are limited. In this study, Gram-negative Escherichia coli Nissle 1917 and Gram-positive Lactiplantibacillus plantarum WCFS1 were encapsulatedin hydrogel matrices, and their growth, metabolic activity, and recombinantgene expression were examined under varying degrees of hydrogel stiffness,achieved by adjusting the polymer concentration and chemical cross-linking.Both bacteria grow from single cells into confined colonies, but moreinterestingly, in E. coli gels, mechanicalproperties influenced colony growth, size, and morphology, whereasthis did not occur in L. plantarum gels.However, with both bacteria, increased matrix stiffness led to higherlevels of recombinant protein production within the colonies. By measuringmetabolic heat from the bacterial gels using the isothermal microcalorimetrytechnique, it was inferred that E. coli adapts to the mechanical restrictions through multiple metabolictransitions and is significantly affected by the different hydrogelproperties. Contrastingly, both of these aspects were not observedwith L. plantarum. These results revealedthat despite both bacteria being gut-adapted probiotics with similargeometries, mechanical confinement affects them considerably differently.The weaker influence of matrix stiffness on L. plantarum is attributed to its slower growth and thicker cell wall, possiblyenabling the generation of higher turgor pressures to overcome restrictiveforces under confinement. By providing fundamental insights into theinterplay between mechanical forces and bacterial physiology, thiswork advances our understanding of how matrix properties shape bacterialbehavior. The implications of these findings will aid the design ofengineered living materials for therapeutic applications.

Engineered livingmaterials (ELMs) integrate synthetic polymerswith engineered cells to create systems that sense, respond, and adaptto their environment. While promising as sustainable alternativesto traditional materials, ELMs remain underexplored for use with photoautotrophicorganisms. In this study, we evaluate the viability of the cyanobacterium Synechococcus elongatus PCC 7942, which convertscarbon dioxide into valuable chemicals using light energy, in threehydrogel matrices previously shown to support heterotrophic cells. S. elongatus remained viable and metabolically activeonly in a hydrogel formed from bovine serum albumin-conjugated acrylates.When engineered to produce 2,3-butanediol (23BDO), encapsulated cellsgenerated 719 mg L–1 over four days. Incorporatingcells increased the compressive modulus of the material, while accumulated23BDO reduced it, indicating that bioproduction influences mechanicalproperties. Fluorescence imaging confirmed high viability and physicalimmobilization. These results establish that cyanobacteria-based ELMscan enable autotrophic chemical production while modulating materialmechanics for sustainable applications.

This study presents an innovative approach to interdisciplinary education by integrating biology, engineering and art principles to foster holistic learning experiences for middle-schoolers aged 11-12. The focus lies on assembling mycelium bricks as engineered living materials, with promising applications in sustainable construction. Through a collaborative group task, children engage in the hands-on creation of these bricks, gaining insights into mycology, biomaterials engineering and artistic expression. The curriculum introduces fundamental concepts of mycelial growth and its potential in sustainable material development. Children actively participate in fabricating 3D forms (negative and positive) using mycelium bricks, thereby gaining practical knowledge in shaping and moulding living materials. This hands-on experience enhances their understanding of biological processes and cultivates an appreciation for sustainable design principles. The group task encourages teamwork, problem-solving and creativity as children collaboratively compose structures using mycelium bricks. Integrating art into the activity adds a creative dimension, allowing participants to explore aesthetic aspects while reinforcing the project's interdisciplinary nature. Conversations about the material's end-of-life and decomposition are framed within the broader context of Nature's cycles, facilitating an understanding of sustainability. This interdisciplinary pedagogical approach provides a model for educators seeking to integrate diverse fields of knowledge into a cohesive and engaging learning experience. The study contributes to the emerging field of nature-inspired education, illustrating the potential of integrating living materials and 3D-understanding activities to nurture a holistic understanding of science, engineering and artistic expression in young learners.