Proceedings of a Workshop—in Brief

Biohybrid Materials and Technologies for Today and Tomorrow

Proceedings of a Workshop—in Brief

Biohybrid materials and devices—which integrate both biological and engineered components— offer exciting opportunities to create new functionalities and support sustainability. Scientists and engineers are exploring biohybrid materials and devices for applications in a broad range of areas including robotics, health, manufacturing, architecture, and agriculture. To highlight emerging science and technology in this area and examine innovation drivers and barriers, the National Academies of Sciences, Engineering, and Medicine hosted a workshop, Biohybrid Materials and Technologies for Today and Tomorrow, January 12-13, 2023.

The workshop was organized under the auspices of the National Academies’ Standing Committee on Biotechnology Capabilities and National Security Needs, which facilitates engagement between the national security community and biotechnology stakeholders to identify advanced biotechnologies with promising capabilities to meet national security needs along with early-stage research that may lead to new or enhanced biotechnologies. Presenters and attendees from government, academia, and industry gathered in person and online to share examples of biohybrid technologies (summarized in Table 1), to identify potential research needs and opportunities, and to discuss issues involved in translating this work into commercial markets and applications. This Proceedings of a Workshop—in Brief provides the rapporteurs’ high-level overview of the event.

Workshop Chair Megan Valentine (University of California, Santa Barbara) offered introductory remarks. She described how biology has long inspired scientists and engineers and today is being used to advance innovations in areas from improving health to building climate resilience to addressing poverty. “Biology continues to offer not only inspiration, but tools, designs, and solutions that can be broadly leveraged to address pressing human needs across diverse application spaces,” said Valentine.

While biohybrid materials and devices hold great potential, Valentine said, unlocking that potential involves addressing several challenges. These products often include new interfaces, infrastructure, and manufacturing and scale-up capabilities. They raise new regulatory questions and may benefit from a workforce with specialized expertise as well as the ability to

TABLE 1
Overview of Example Technologies Discussed at the Workshop

NOTE: This table summarizes examples of technologies shared by workshop participants and should not be interpreted as consensus conclusions or recommendations of the National Academies.

work in interdisciplinary teams. To explore emerging opportunities in biohybrid materials and devices along with pathways to navigate these challenges, Valentine said the workshop was designed to bring together people who are thought leaders in their field to exchange experiences and ideas, inspire collaborations, and articulate a vision for the path ahead.

MANUFACTURING MATERIALS WITH LIVING ORGANISMS

The workshop opened with a panel on methods to create materials with living organisms moderated by Alshakim Nelson (University of Washington), including a keynote presentation by Ginger Krieg Dosier (Biomason).

Biomason uses microbes to make cement. In contrast to the energy-intensive process for making Portland cement (the binding agent in traditional concrete), Biomason harnesses the natural capability of living, nonpathogenic organisms to create calcium carbonate, the chemical compound found in seashells and other structures, to create structural cement at ambient temperatures in a controlled and scalable process.

Dosier indicated that her company Biomason aims to achieve its emissions-reductions goals in the Portland cement market by integrating their bio-based cement into relevant existing markets that include precast products in flooring, walls, and other applications, taking advantage of existing infrastructure and leveraging partnerships to expand production to a target of more than 700 plants worldwide. The company is also exploring microbe-based methods to create ready-mix biobased concrete, dust control agents, grown-in-place underwater structures, and biobased tiles and pavers.

Dosier highlighted challenges related to both the business environment and the underlying technology for biobased concrete. Biobased products are advancing faster than government regulations, and Dosier said that moving the needle in the concrete industry will likely require changes across the ecosystem, including changes to government mandates. She and some other workshop participants also noted that biobased materials can continue to contain live organisms after manufacturing is complete, which can have the benefit of supporting self-healing capabilities but can also pose a risk of dormant organisms or spores escaping into the environment. She suggested that the field would benefit from more predictive modeling capabilities, which would allow researchers to explore different permutations that may be suitable for different applications. To increase sustainability, she said it is important to develop ways to use wastes, such as mine tailings, as source materials, and to consider the expected lifespan of a material or structure—and what happens once that lifespan ends—as part of material design. Finally, Dosier noted that developing new materials and new ways of manufacturing them, requires new testing strategies and suggests a need for new standards. Working through these challenges, she said, involves a willingness to learn and adapt.

Neel Joshi (Northeastern University) and Anne Meyer (University of Rochester) discussed other approaches to leveraging bacteria to make materials. Using Curli fibers, part of the E. coli extracellular matrix, as a scaffold, Joshi’s team has developed ways to genetically program the functionality of biopolymer structures with rational design. Meyer described her team’s method for the three-dimensional (3D) printing of bacteria with sub-millimeter precision to create living structures in specific spatial arrangements.¹ Both speakers discussed how these approaches with microorganisms can be used to create biocompatible and biodegradable films, gels, inks, and other structures with properties such as filtering, adhesion, sensing, and light-harvesting.^2,3,4,5

David Breslauer (Bolt Threads) described his company’s development of materials using synthetic spider silk and the mycelium threads that comprise mushrooms’ rootlike structures. The company’s synthetic spider silk-based products, Microsilk and B-silk, are being developed as a strong and lightweight thread and as water-absorbing beads for potential use in personal care products, respectively, but these are still in early stages of commercialization. Mylo, its mycelium-based product, has found a niche in the growing market as a leather alternative. By focusing on the microstructures of products with desired attributes—such as the suppleness of leather or the draping behavior of fabrics—Breslauer said the company finds opportunities to replace traditional materials with more sustainable alternatives.

Speakers discussed challenges and future research directions to further refine biomanufacturing techniques. Joshi said that improving methods such as directed evolution and rational design will help increase the capacity to engineer biomaterials with prescribed functions. Meyer pointed to a need to improve the robustness of bacteria-based materials, noting that microbes’ limited lifespan can pose a challenge for applications in which it is important for bacteria to

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remain alive, for example applications that depend on the bacteria to retain a material’s physical integrity. Speakers noted, the overall lifespan of a material or product is also an important consideration, as the capacity to biodegrade quickly can be an asset for applications such as packaging materials but detriment for applications such as construction. Meyer also noted that containment of bacteria can pose an issue, especially with more porous structures such as gels.

Participants also discussed issues around research translation, scale-up, and finding a market niche. For 3D printing, Meyer said the tradeoff between volume and resolution is an important consideration for scale-up. To address some of the physical challenges of working with biological materials at scale, Joshi suggested learning from established industries that have solved similar problems, such as the paper industry’s methods for creating solids from liquid pulp. All the speakers noted that biobased materials face headwinds in achieving broad market acceptance and penetration, since many of these technologies are early-phase and will be expensive initially. To speed adoption and reduce costs, Joshi suggested a need for policies to incentivize demand for sustainable products. Breslauer underscored the importance of sustainability as a major driving force in the biomaterials space, both for the manufacturing methods used and for the end products.

DYNAMIC AND RESPONSIVE BIOHYBRID TECHNOLOGIES

Biological systems offer opportunities for programmability, responsiveness, adaptability, and other complex functions. Robert Full (University of California, Berkeley) moderated a session exploring dynamic and responsive biohybrid technologies.

The actions of microorganisms, said Taylor Ware (Texas A&M University), can create macro-level changes, as illustrated in the activity of yeast in making bread dough rise. He discussed his team’s development of stimulus-responsive materials that harness this capability by using microbes to trigger a structural change under specific circumstances, such as the presence of light.⁶

This approach can be useful for creating shape-changing structures as a basis for soft, lightweight devices, though tuning these systems to respond only to certain stimuli in a complex environment remains an important challenge, Ware said. At the molecular level, Abdon Pena-Francesch (University of Michigan) shared his work using proteins as a structural basis for dynamic materials. By learning from natural proteins such as those present in squid suckers, his team uses synthetic proteins to create materials with properties such as elasticity and self-healing capabilities.^7,8 Ultimately, he said that integrating such bioinspired materials into technologies such as wearable sensors, soft robots, and microrobots can enable dynamic devices with better self-assembly, self-repair, and end-of-life management capabilities than traditional engineered materials, as biological materials have intrinsic self-regulation mechanisms to sense and process information from the environment and change their structure, change their properties and their overall function to adapt to those environments, which is something currently missing in most engineered and human-made materials.

Muhammad Hussain (Purdue University) highlighted emerging opportunities for connecting electronic components with biological systems for adaptive, responsive, and reconfigurable electronics. Such approaches, he said, can form the basis for new tools of scientific discovery such as intelligent sensing systems; electronics for biomedical applications; devices capable of operating in extreme environments; and rapid manufacturing techniques for personalized electronics. Examples include the crab-mounted Bluefin system for marine monitoring,⁹ plant wearables,¹⁰ the Shohay biosensing and drug delivery platform,¹¹ and low-cost

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paper-based environmental sensors.¹² Hussain, Ware, and a few other participants noted that the aqueous nature of most biological systems can pose challenges for interfacing between biological elements and electronic components; Hussain said the packaging material for the electronic components is critical and suggested materials researchers should partner with practitioners to develop biocompatible packaging that can retain functionality for extended periods.

Speakers identified opportunities for research programs to further advance bioinspired, bio-interfaced, and biohybrid adaptive materials. Ware noted that yeast capsules for beer production are already poised for commercialization, but for many areas, such as dynamic biomaterials for health applications, there is a need for significant investment in translational research. Pena-Francesch said that further research is needed to navigate the tradeoff between kinetics and function. Hussain suggested initially focusing on building simplistic systems with a minimal number of components and materials to achieve more functionalities in the near term. To accelerate translational research in this area moving forward, Pena-Francesch and Ware stressed the importance of supporting multi-disciplinary teams of biologists and engineers, which often requires sustained funding over long timeframes.

PLANT-BASED TECHNOLOGIES AND FUNCTIONAL MATERIALS

Plants have unique adaptations and are crucial to the well-being of humans and ecosystems. Valentine moderated a session examining how plants and plant-derived materials can be incorporated into devices for a variety of applications.

Sensors to monitor plants’ microclimate and detect early signs of stress, along with mechanisms for dynamically controlling plant physiology, can help to optimize the use of resources for growing crops. Eleni Stavrinidou (Linköping University) highlighted how plant-based sensing capabilities and bioelectronic devices can support precision agriculture, helping to meet the world’s food needs while reducing greenhouse gas emissions and land use impacts. Her team’s electro-organic sugar sensor, for example, provides insights into plant growth that cannot be achieved with traditional invasive methods.¹³ Stavrinidou also described potential plant-based approaches for a range of low-power, environmentally-friendly technologies.¹⁴ To advance these efforts, she said it will be important to facilitate communication between plant scientists and engineers, partner with agriculture experts to ensure technologies are practical for adoption, and invest in basic research to elucidate the metabolic pathways that may be targeted for monitoring and interventions.

Plant-based materials can also be used to replace petroleum-based products. Chiara Daraio (California Institute of Technology) shared her work leveraging plants and algae as a basis for materials, and noted the underexplored and underutilized richness in diversity of plants in the material science community. To tap into plants’ diverse properties without relying on keeping material alive, Daraio’s team focuses on capturing and “immortalizing” these properties, often by creating biological matrices using plants or algae-derived material along with synthetically derived reinforcements.¹⁵ Materials created this way can have many of the benefits of natural plant-derived materials such as wood, but with additional features such as moldability, printability, conductivity, and self-healing.

There is also much to learn from the way plants move and support themselves. Thomas Speck (Universität Freiburg) described his team’s use of plant-inspired physical forms for architectural and biomedical applications. Their Flectovin® and Flectofold systems are hydraulically-powered shading systems based on the torsional buckling motion that the bird-of-

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paradise flower uses to create a perch for birds and the trapping motion of the carnivorous waterwheel plant, respectively.¹⁶ The team also built a bioinspired pavilion using resin-covered flax fiber entwined in an arrangement inspired by the strategies cacti use to create strong and lightweight structures. In the medical space, Speck described a wrist splint that uses a helical structure, inspired by the twining behavior of vines, to wrap around the wearer to create custom orthotic devices.¹⁷

The plasticity, sensing, and embedded energy properties of plants can also inspire new strategies for robotics. Barbara Mazzolai (Istituto Italiano di Tecnologia) described her team’s efforts to apply plant behaviors such as growth, climbing, seed dispersal, and movement to advance robotic capabilities including grasping and manipulation, exploration and monitoring, and green energy production. For example, they created robots that mimic a plant root tip, demonstrating the ability to move in response to environmental stimuli.¹⁸ They also created artificial microhooks, inspired by the ways vines anchor and climb, and incorporated them into robots for movement across different substrates and into leaf-mounted stress sensors to monitor plant health.^19,20 The team is also leveraging seed dispersal strategies to develop soft biodegradable robots for environmental monitoring and using plant-hybrid wind energy harvesters to generate electricity.^21,22

Speakers highlighted many advantages and future possibilities for plant-inspired and biohybrid materials and devices, along with some key challenges. Daraio said that better understanding plant functionalities can help researchers find ways to harness those functions in ways that are more automated and systematized, for example by enabling computer-aided design strategies instead of the largely trial-and-error approaches used currently. Stavrinidou noted that calibration remains a challenge for plant-based sensors and devices that operate differently from traditional analytical tools, given the lack of ground-truth data to compare against. While plants could theoretically offer a useful platform for chemosensing applications, Mazzolai and Stavrinidou said this would depend on the ability to generate a readable output of the signals plants produce, which is not currently feasible. Speck and Mazzolai noted that machine learning methods can help researchers to validate and better understand the data generated by plant-based sensors. Finally, Mazzolai noted that plant-to-plant communication networks (mediated by fungi) could offer new opportunities for bioinspired artificial systems, but there is a need for fundamental research into how these complex networks operate.

BIOROBOTICS AND HEALTH

Biohybrid materials and devices can be especially well suited for applications to support human health. Full moderated a session examining biorobotics and emerging opportunities in the design, manufacturing, and applications of biohybrid materials in health and medicine.

Zhenan Bao (Stanford University) gave a keynote presentation on electronic skin technology. Her team builds soft, neuromorphic electronic skins capable of sensing pressure and other types of signals, processing and interpreting these signals, and then providing meaningful feedback. These devices are designed to feel like skin and be comfortable and biocompatible, while having large sensing arrays and the capability to autonomously process enormous amounts of data with low power consumption. Electronic skins could find application in a variety of areas, for example, as

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prosthetics for people with touch-related disorders, to enhance the sensing and manipulation capabilities of robots, or as internal or external sensors for medical monitoring. A continuous, noninvasive blood pressure monitor for infants is currently under review by the U.S. Food and Drug Administration.

Bao described how the team experimented with a variety of materials and designs to create conductive, photopatternable polymers with nanoconfined structures, resulting in stretchable integrated circuits that can be manufactured with optical microlithography.^23,24 With high-density transistor arrays, these devices can detect force, temperature, shear, and other properties with high precision. Bao highlighted opportunities to use this technology to build implantable devices that stretch and grow with internal organs, bioactive embedded sensors with electrical stimulation capabilities, devices with rapid individualized learning, and more.

In terms of future research directions, Bao said that the ability to provide power wirelessly from an external source remains a key area of research for implantable devices. Scientists have made some progress toward developing soft, stretchable batteries, but this also entails more development. Now that the team’s e-skin devices are beginning to achieve sufficient performance, Bao said that understanding long-term biocompatibility will become a growing area of focus, as well as device robustness, potential self-healing capabilities, and biodegradability. To accelerate this work and its translation, Bao said manufacturing capabilities will be critical and highly effective interdisciplinary teams will be needed to drive the integration of biological and engineered devices.

If robots are to become ubiquitous in the world, said Victoria Webster-Wood (Carnegie Mellon University), they could be made from materials that are renewable and biodegradable to avoid creating waste, as well as biocompatible to interface with humans and ecosystems. Recognizing that biological systems already meet many of these criteria, she described her team’s efforts to leverage biomaterials, biomanufacturing processes, and biohybrid robots to understand and learn to emulate adaptable, responsive, and self-healing biological materials and systems. Working with collagen and extracellular matrix proteins, Webster-Wood’s team uses proteins as threads and scaffolds in 3D-printed alginate biomaterials. With help from computer vision and computational modeling collaborators, they use models to optimize designs and develop controllable manufacturing processes for these materials.²⁵ John Rogers (Northwestern University) stressed that material and structure are critical to integrating robotics with biological systems, which requires moving away from the rigid, two-dimensional (2D) structures of conventional robotics and toward more 3D flexible forms that can be integrated in or around soft living tissues.

Speakers shared recent advances in biorobotics. Rogers described his team’s work on a ringlike structure of engineered tissue designed to monitor cardiac function and deliver drugs,²⁶ remote controlled muscle-driven biobots,²⁷ and implantable wireless optogenetic devices. Webster-Wood shared her team’s efforts in developing living muscle as a robotic actuator, as well as in developing biohybrid controllers using living neurons as robotic controllers.²⁸ Ritu Raman (Massachusetts Institute of Technology) described her work developing engineered skeletal muscle tissues that are responsive to electrical signals and light.²⁹ Her team is exploring how

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this approach be used to create trainable, self-healing muscle-powered robots, as well as how light-stimulated muscle cells can be used to study muscle damage and healing.

Speakers discussed several key challenges and areas for future research. Getting biorobots out of the lab and into the world will require additional work to refine force capabilities, programmability, and flexibility, along with scalable manufacturing methods and packaging strategies to protect and maintain living materials, Webster-Wood said. Rogers and Bao agreed, noting that developing long-lived products that can withstand or remain sealed off from an aqueous environment remains a critical challenge, and Bao added that interfacing between soft and rigid materials is another challenge.

Maintaining a source of energy is an important consideration for many biohybrid technologies, particularly for implantable devices. In muscles, Raman said that sugar is the main energy source and has the advantage of being renewable and biodegradable in living systems. However, Raman noted that muscle actuators can have unpredictable lifespans and suggested that further research into the pathways that influence their longevity could help to inform strategies to either prolong their lifespans or, on the flip side, facilitate biodegradation. Rogers added that some biological organoids or implants require vasculature to maintain living components and pointed to a need for 3D microfluidics approaches to achieve this. For electronic components, Webster-Wood and Bao said it is important to think through energy needs when selecting materials and designing computational systems to minimize power requirements, in addition to making progress toward stretchable biocompatible batteries. Embedding preprocessing capabilities in the devices—mimicking the way synaptic junctions preprocess signals sent to the brain—could also improve performance and reduce computation needs and power consumption, Bao noted.

To guide future investments and research directions, Rogers underscored the need to consider what features biohybrid robots offer and why biomaterials are useful, focusing on leveraging unique properties such as self-healing, self-powering, feedbacks, learning, and cooperating, rather than simply attempting to replicate what conventional electronics can already achieve. Integrating multiple components together into a multifunctional system is an important goal but remains challenging. Bao said that a systems-level approach will be needed to move from individual parts and components to fully integrated, responsive biohybrid robots. “Currently, there are a lot of great ideas of individual function or individual parts. To really build biohybrid robots, that’s a system level challenge and it requires many different disciplines to really work together,” said Bao.

Speakers also discussed the interplay between basic science and applications in fueling advances. Webster-Wood noted that the tools being developed to enable basic science in this field could find opportunities for commercialization, such as in tissue engineering applications. Conversely, biorobots can be useful as model systems for studying biology, potentially providing a “system-on-a-chip” platform to enhance basic science. Raman agreed, adding that the near-term applications of these technologies are likely to be in health and medicine, but said that untethered robotics technologies (i.e., those that do not rely on a direct physical connection to external power or other equipment) will be relevant to a wide range of other fields, as well. Bao said that it is helpful to focus on long-term goals for driving research but it is also helpful to focus on simpler and more established approaches for applications and commercialization in the near term. Rogers noted that it can be hard to predict the ultimate applications for major technological innovations, as sometimes these applications do not emerge until decades later.

BIOHYBRIDS IN THE BUILT ENVIRONMENT

Biohybrid approaches are also being explored for applications in large-scale structures. Fiorenzo Omenetto (Tufts University) moderated a session on biohybrids in the built environment. Biohybrids offer an opportunity to replace or augment entire families of materials such as plastic, concrete, steel, and glass with products that are

more sustainable, responsive, and flexible. Laia Mogas-Soldevila (University of Pennsylvania) shared her team’s work developing responsive and interactive biohybrid materials for clothing and buildings, including leather-like silk protein materials which can be tuned to different purposes and printable inks that change color in response to particular features in the environment.^30,31 Felecia Davis (Penn State University) described how her team develops knitted fungi-derived large-scale structures by using fungi mycelium as a natural fiber to create industrially knit formwork for lightweight, biodegradable composites and structures.

Biohybrid materials could dramatically alter methods of production for a variety of products. Tomás Diez (Fab City Foundation) described how his organization’s vision for creating distributed networks of locally based production could aid this transition by supporting a shift from the current product-in-trash-out paradigm to a more sustainable and adaptable data-in-data-out model. Mogas-Soldevila noted that biohybrid materials could offer opportunities to transform waste streams—for example, cellulose from agricultural wastes or chitin from discarded shells in the seafood industry—as source materials. Davis added that the capability to process and construct new biomaterials at the local level will be important for widespread adoption, as opposed to the current concentration of these processes in high-tech labs.

While biohybrid materials open exciting possibilities, miscommunication and hype can lead to problems. Mogas-Soldevila noted that the drive to get products into the marketplace quickly can lead engineers to incorporate petroleum-based additives, which can help to stabilize biomaterials and protect against factors such as temperature and humidity but can also move the product away from being entirely biobased. While this is not necessarily bad, it is important to be transparent in communicating with the public about both the production process and the end product to avoid overselling biohybrid products. Diez and Davis agreed that hype can be an issue, although Davis also underscored the importance of building public awareness of the benefits of biohybrid products and to find ways to embed them into people’s day to day lives. Diez added that convenience tends to be one of the most powerful drivers in the adoption of new technologies and products, and Mogas-Soldevila stressed that attractiveness and appeal will be essential to gain acceptance in the marketplace.

TRANSLATING FROM BENCH TO MARKET

Even as researchers continue to pursue fundamental research questions, innovators and entrepreneurs are actively moving biohybrid materials and devices into applications in a variety of areas. Valentine moderated a session examining the opportunities and roadblocks of translating biohybrid materials and devices from the laboratory to commercial markets.

Don Ingber (Harvard Wyss Institute) shared insights from his institute’s model for research commercialization and entrepreneurship, which includes 11 core faculty members and enables about 25% of Harvard’s intellectual property (IP) and startups annually. Key to this success, Ingber said, is that the institute gives researchers access to a network of experts in finance, law, manufacturing, and business in an environment designed specifically to foster product development—in contrast to the “just do the best science” approach more common in academic research. Ingber emphasized the importance of finding “pulls” (problems that need to be solved) rather than “pushes” (technologies seeking application) to inform business development investments. Thinking about business opportunities and constraints early in the translational process is essential, he said. At the Wyss Institute, in-house experts provide strategic support on IP issues to help researchers understand what can be patented and where the highest-impact business opportunities lie. Interdisciplinary teams and strong funding streams are also critical, Ingber said, pointing to organs on a chip (microfabricated chips with living cells that demonstrate organ-level functions) as one example

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which has required broad understanding across many different science and engineering fields and largely been fueled by DARPA funding. The institute also connects researchers with the instrumentation they need for rapid prototyping to work out manufacturing methods and facilitates collaborations with regulatory agencies to ensure products meet requirements necessary for approval.

Venture capital (VC) investment is often a key gateway for technology commercialization. Pae Wu (SOSV’s IndieBio) offered a VC investor perspective on moving biohybrid technologies from the lab to the market. When assessing the commercial potential of a technology, investors seek products that people will value and want to use. IndieBio has invested in many companies that harness biological processes to produce products or create new functionality; examples include Upside Foods, which manufactures cultured meat; Perfect Day, which uses organisms to make whey proteins for their animal-free ice cream brand, Brave Robot; Canaery, which is developing a biohybrid smelling technology using a nose-computer interface that digitizes and interprets scents entering an animal’s olfactory system to identify compounds in the environment; Vertical Oceans, which speeds shrimp farming; and Infinite Elements, which uses biological processes to extract rare Earth elements from spent magnets, among others. Biohybrid technologies often face technical challenges related to navigating interfaces between components that are wet and dry, hard and soft, passive and active, and fast and slow. Wu noted that it is often possible to overcome these challenges with the right investments, but justifying those investments requires confidence that the ultimate product will find a market. Solving an unmet need is therefore crucial to investment decisions. “The problem that you’re solving really, really matters to us, and that has everything to do with whether or not we can invest and see a path for these technologies to grow,” said Wu. “Bridging that ‘valley of death’ is about finding that correct problem to solve. In the end, none of this really matters if you’re not actually solving a problem that anybody cares about.”

Speakers noted that transitioning to entrepreneurship or industry can be challenging for academics because it requires a more nimble and near-term oriented way of working. On the plus side, the pressures of investment cycles can spur collaborations and lead to new breakthroughs. “There is nothing quite like the boiler room of existential crisis, of your company not existing if you don’t figure it out,” said Wu. “Too much comfort can make it hard to take the next steps sometimes.” Ingber agreed and noted that fostering interdisciplinary teams is critical in overcoming barriers during this process. “Creating a team is equally important, if not more important, than the technology when you’re commercializing, and I think that’s one thing academics never really appreciate,” he said.

Speakers discussed how many biohybrid technologies are being pursued to meet sustainability goals but are likely to find it difficult to compete with established products, at least initially. Wu, Ingber, and Breslauer noted that intervention from governments, foundations, or other actors can help to speed development and adoption of more sustainable alternatives, such as by establishing guaranteed contracts to incentivize product development, issuing mandates to create a market pull based on sustainability criteria, and acting quickly to adjust regulations and testing processes to accommodate new types of materials and products.

ETHICS, RISKS, AND OPPORTUNITIES FOR INCLUSION

The design and use of biohybrid materials and devices raise unique risks and ethical considerations. Deepti Tanjore (Advanced Biofuels and Bioproducts Process Development Unit [ABPDU]) moderated a breakout session examining these issues and how diverse perspectives and communities can be incorporated into innovations and their commercialization going forward.

Several participants identified a range of possible risks and ethical issues in biohybrids research and applications. For instance, materials that incorporate living organisms could potentially allow the release of allergens, pathogens, or other organisms capable of causing health or environmental harm and could even create vulnerabilities to bioterrorism or new types of

attacks. Many of these technologies also raise animal welfare considerations. A few participants suggested it may be important to consider how regulatory or oversight bodies can assess such risks and provide appropriate governance.

Some participants also noted that disruptive biotechnologies raise potential concerns related to environmental justice and equity. Since this field is likely to draw upon biological resources from around the world and the commercialization of these technologies is often pursued through a Western lens, it is possible that the risks of these technologies could accrue disproportionately in less-resourced communities while the benefits accrue disproportionately in more-resourced communities. Some participants said that it will be important to assess such risks, appropriately regulate activities, and invest in scalability to decrease costs and thereby increase the accessibility of these technologies in a broad range of communities. In addition, a few participants noted that it is valuable to incorporate input from intended users or members of the workforce during the development of technologies to design products with sensitivity to the needs and cultures in which they will be used. Finally, several participants observed that misinformation is likely to be a barrier to adoption and suggested the need for proactive and transparent public communication and education.

EDUCATION AND WORKFORCE CONSIDERATIONS

Inclusion is also an important consideration for supporting a robust, diverse, and interdisciplinary workforce that will drive future advances in the field. In breakout discussions facilitated by Fiorenzo Omenetto (Tufts University), participants examined gaps and opportunities in workforce development. Throughout the workshop, many participants stressed the importance of interdisciplinary teams in advancing biohybrid technologies. To facilitate this, a few participants suggested incorporating cross-disciplinary opportunities into graduate curricula, both in formal ways (such as through interdisciplinary studies certificates or “externships” outside of one’s area of study) and through changes in how various topics are taught to offer graduate students the opportunity to develop deep expertise in their field, while also gaining exposure and experience with other disciplines and industries.

Several participants also pointed to a disconnect between the skills students gain in typical science graduate programs and the skills they need to succeed in industry and suggested a renewed focus on preparing students for working in teams and pursuing career pathways beyond academia. Engagement with community colleges, national laboratories, and efforts at the K-12 level also play an important role in the workforce pipeline and engagement with interdisciplinary, solutions-oriented science and engineering careers. A few participants suggested that philanthropic foundations could be helpful in enhancing educational pathways in addition to partnerships among government, academia, and industry. “Education is absolutely crucial. Biomaterials in general provide an amazing opportunity and a natural opportunity to start training the next generation of people that will think and act globally,” Omenetto said.

INNOVATION ECOSYSTEM AND UNMET NEEDS

During the final breakout session of the workshop, participants highlighted their key takeaways and examples of unmet needs for the biohybrid field, including the development of robust, standardized, and high throughput testing methods for biohybrid materials to enable comparison and optimization during development, regulation during production, and safe use during deployment. Some participants emphasized measurement techniques and standards and mentioned lessons could be learned from the development of ceramics and metals at scale. Some participants mentioned compatibility with aqueous environments for biorobotics applications and the ability to leverage native materials already found in the ecosystem, rather than introducing new materials. Several participants also pointed to material control and modulation of microorganisms as unique risks associated with biohybrid materials and technologies. Regarding the innovation ecosystem, some participants noted that the existing reward structures in academia may create obstacles to interdisciplinary collaborations and limit opportunities for sustained research funding across disciplines.

DISCLAIMER This Proceedings of a Workshop—in Brief was prepared by ANNE JOHNSON, TRISHA TUCHOLSKI, and ANDREW BREMER as a factual summary of what occurred at the workshop. The statements made are those of the rapporteurs or individual workshop participants and do not necessarily represent the views of all workshop participants; the planning committee; or the National Academies of Sciences, Engineering, and Medicine.

WORKSHOP PLANNING COMMITTEE MEGAN T. VALENTINE (Chair), University of California, Santa Barbara; ALSHAKIM NELSON, University of Washington; FIORENZO G. OMENETTO, Tufts University; ROBERT J. FULL, University of California, Berkeley; and DEEPTI TANJORE, ABPDU

REVIEWERS To ensure that it meets institutional standards for quality and objectivity, this Proceedings of a Workshop—in Brief was reviewed by MEGAN VALENTINE, University of California, Santa Barbara and VICTORIA WEBSTER-WOOD, Carnegie Mellon University, and LAUREN EVERETT, National Academies of Sciences, Engineering, and Medicine, served as the review coordinator. We also thank staff member JULIE PAVLIN for reading and providing helpful comments on this manuscript.

SPONSORS The Standing Committee on Biotechnology Capabilities and National Security Needs, under which this workshop was organized, is supported by the U.S. government.

For additional information regarding the workshop, visit https://www.nationalacademies.org/our-work/biohybrid-materials-and-technologies-for-today-and-tomorrow-a-workshop.

Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2023. Biohybrid Materials and Technologies for Today and Tomorrow Proceedings of a Workshop—in Brief. Washington, DC: The National Academies Press. http://doi.org/26910.

Division on Earth and Life Studies Copyright 2023 by the National Academy of Sciences. All rights reserved.