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Nanoengineered Shape-Memory Hemostat

Uncontrolled hemorrhage is the predominant cause of preventable combat deaths. Various biomaterials serve as hemostatic agents due to their procoagulant or absorptive activity. However, these biomaterials often lack expansion capabilities, which severely limits use in noncompressible wounds. This study combines a hemostatic nanocomposite with a shape-memory polymer foam to design a composite material with both hemostatic and physical expansion properties. This composite is fabricated in two formulations: a foam externally coated in a highly concentrated nanocomposite (“coated composite”) and a foam containing a diluted nanocomposite infused throughout its pores (“infused composite”). Both formulations retain the shape-memory foam's expansion property. Further, the coated composite shows improved fluid uptake (>2-fold) versus infused composites or foam. The nanocomposite component dissociates from the foam under degradative conditions, with the foam remaining stable for 30 days. Hemostatic studies illustrate that the coated composite reduces the clotting time by ≈20%. Alternatively, the infused composite improves clotting over a larger distance (up to ≈2× distance from the composite). These results signify a modular hemostatic ability: the coated composite reduces clotting and improves fluid uptake, while the infused composite achieves diffuse clotting and maintains mechanical properties. Thus, these materials pose a strong potential for use in noncompressible wounds.

60 APPLIED LIFE SCIENCES

The effect of interstitial air on the in vitro thrombogenicity of ePTFE vascular grafts

Gas trapped in the interstices of the biomaterials used for vascular prostheses causes thrombosis, and the process of eliminating this gas is known as denucleation. An apparatus was developed for testing in the in vitro effects of denucleation on 4 mm I.D. expanded polytetrafluoroethylene (ePTFE) Vitagraft (Johnson and Johnson). The apparatus was designed to ensure that neither the blood nor the grafts came in contact with air. Blood from a single donor was incubated with control and denucleated grafts for 5, 10, 15, 20, and 30 minutes. The thrombus volume in the graft lumen was measured with a computer assisted videometric system. Little thrombus formed by 5 or 10 minutes, but there was less thrombus in the denucleated graft than in the control graft at all times. The differences were statistically significant at 15 and 20 minutes (p < 0.05). Denucleation nearly doubled the thrombus formation time. Thrombus was more adherent to denucleated grafts than to control grafts. These results are consistent with in vivo observations in the rat where denucleation decreased thrombus formation and increased patency duration.

NASA Discipline Number 04-10

Biomaterials Out of Thin Air: in Situ, On-Demand Printing of Advanced Biocomposites

Upmass is the single most significant limitation of our current space mission capability. Although biomaterials and biocomposites have mass, strength, flexibility, and self-healing properties that could significantly reduce upmass, their use is limited by the following drawbacks: Expensive, specific production. Many biomaterials can only be produced as part of significant support ecosystem; Inaccessible functional customization. The grain of wood, the porosity of bone, and so on are an integral part of the materials' desired mechanical properties, but are not deterministic when the material is naturally grown; Limited compositions. Most biomaterials (unlike metal, plastic, etc.) cannot be easily combined or modified to produce new materials. This project builds on recent advances in: Synthetic biology. Libraries of standardized genetic parts which can be used for controlled cellular material production, delivery, and binding; 3D printing. Commercial off-the-shelf components which can be used to make of a pico- to nanoliter cell deposition system; Tissue engineering. Proven cell-compatible support hydrogels and scaffolds can be modified to bind the deposited biomaterials of interest. Objectives: Feasibility and benefit analysis. Two mission contexts span the concept's scope (see below); Proof-of-concept demonstration. A simple grid of two proteins, fluorescent for easy detection, to validate the core technology concept; Proposed implementations for follow-on work. Avenues for future work on each core component (host cell, production control, material delivery, material binding, etc.); Complementary studies exploration. A survey of other emerging areas (in situ resource utilization, protein engineering, etc.) with the potential to multiply our technology's impact. Potential Impacts: This application could dramatically expand manufacturing capabilities on Earth and in space: In situ resource utilization. A far greater range of materials and products will be available from the limited palette offered by in situ resource extraction techniques; Reduced equipment and material upmass for off-Earth habitats. Ready- to-use highly specialized construction materials (radiation hardened, compressive/tensile, light or dense) from an extremely low starting mass; Structured biomaterial production. New ready-to-use macro, micro, and molecular manufacturing techniques for traditional biomaterials such as wood, bone and shell; New and novel biocomposite creation. The ability to create completely novel material composites from any base material that cells can be engineered to produce. Suggested Mission Contexts: ISS part manufacturing. A 'minimal working example' making a finished biomaterial part aboard the International Space Station; A long-term Mars habitat. 'Cradle-to-grave' use at a hypothetical Mars habitat, covering everything from tools to construction materials. Alternate Abstract: Imagine being able to print anything from tools and composite building materials to food and human tissues. Imagine being on Mars with the ability to replace any broken part, whether it's a part of your spacesuit, your habitat, or your own body. We propose a technique that would allow just that. By printing 3D arrays of cells engineered to secrete the necessary materials, the abundant in situ resources of atmosphere and regolith become organic, inorganic, or organic-inorganic composite materials. Such materials include novel, biologically derived materials not previously possible to fabricate.

habitats

Biomaterials Out of Thin Air: in Situ, On-demand Printing of Advanced Biocomposites

Upmass is the single most significant limitation of our current space mission capability. Although biomaterials and biocomposites have mass, strength, flexibility, and self-healing properties that could significantly reduce upmass, their use is limited by the following drawbacks: Expensive, specific production. Many biomaterials can only be produced as part of significant support ecosystem; Inaccessible functional customization. The grain of wood, the porosity of bone, and so on are an integral part of the materials' desired mechanical properties, but are not deterministic when the material is naturally grown; Limited compositions. Most biomaterials (unlike metal, plastic, etc.) cannot be easily combined or modified to produce new materials. This project builds on recent advances in: Synthetic biology. Libraries of standardized genetic parts which can be used for controlled cellular material production, delivery, and binding; 3D printing. Commercial off-the-shelf components which can be used to make of a pico- to nanoliter cell deposition system; Tissue engineering. Proven cell-compatible support hydrogels and scaffolds can be modified to bind the deposited biomaterials of interest. Objectives: Feasibility and benefit analysis. Two mission contexts span the concept's scope (see below); Proof-of-concept demonstration. A simple grid of two proteins, fluorescent for easy detection, to validate the core technology concept; Proposed implementations for follow-on work. Avenues for future work on each core component (host cell, production control, material delivery, material binding, etc.); Complementary studies exploration. A survey of other emerging areas (in situ resource utilization, protein engineering, etc.) with the potential to multiply our technology's impact. Potential Impacts: This application could dramatically expand manufacturing capabilities on Earth and in space: In situ resource utilization. A far greater range of materials and products will be available from the limited palette offered by in situ resource extraction techniques; Reduced equipment and material upmass for off-Earth habitats. Ready- to-use highly specialized construction materials (radiation hardened, compressive/tensile, light or dense) from an extremely low starting mass; Structured biomaterial production. New ready-to-use macro, micro, and molecular manufacturing techniques for traditional biomaterials such as wood, bone and shell; New and novel biocomposite creation. The ability to create completely novel material composites from any base material that cells can be engineered to produce. Suggested Mission Contexts: ISS part manufacturing. A 'minimal working example' making a finished biomaterial part aboard the International Space Station; A long-term Mars habitat. 'Cradle-to-grave' use at a hypothetical Mars habitat, covering everything from tools to construction materials. Alternate Abstract: Imagine being able to print anything from tools and composite building materials to food and human tissues. Imagine being on Mars with the ability to replace any broken part, whether it's a part of your spacesuit, your habitat, or your own body. We propose a technique that would allow just that. By printing 3D arrays of cells engineered to secrete the necessary materials, the abundant in situ resources of atmosphere and regolith become organic, inorganic, or organic-inorganic composite materials. Such materials include novel, biologically derived materials not previously possible to fabricate.

habitats

3D Printing of Advanced Biocomposites on Earth and Beyond

Human exploration off planet is severely limited by the cost of launching materials into space and re-supply. Thus materials brought from earth must be light, stable and reliable at destination. Using traditional approaches a lunar or Mars base would require either transporting a hefty store of metals or heavy manufacturing equipment and construction materials for in situ extraction; both would severely limit any other mission objectives. Long-term human space presence requires periodic replenishment, adding a massive cost overhead. Even robotic missions often sacrifice science goals for heavy radiation and thermal protection. Biology has the potential to solve these problems because it can replicate and repair itself, and do a wide variety of chemical reactions including making food, fuel and materials. Synthetic biology can greatly enhance and expand life's evolved repertoire. Using natural and synthetically altered organisms as the feedstock for additive manufacturing could one day make possible the dream of producing bespoke tools, food, smart fabrics and even replacement organs on demand. To this end our lab has produced a proof-of-concept bioprinter with nearly one-cell resolution. Genetically engineering yeast cells to secrete bioproducts subsequent to printing allows the potential to make biomaterials with a fine microstructure. Imagine a production system that, at a few micron scale resolution, can add mollusk shell for compressive strength per unit mass, spider silk or collagen for tensile strength per unit mass, and potentially biologically-deposited wires. Now imagine what new products can be enabled by such a technology, on earth or beyond

Metals

3D Printing of Advanced Biocomposites on Earth and Beyond

Human exploration off planet is severely limited by the cost of launching materials into space and re-supply. Thus materials brought from earth must be light, stable and reliable at destination. Using traditional approaches a lunar or Mars base would require either transporting a hefty store of metals or heavy manufacturing equipment and construction materials for in situ extraction; both would severely limit any other mission objectives. Long-term human space presence requires periodic replenishment, adding a massive cost overhead. Even robotic missions often sacrifice science goals for heavy radiation and thermal protection. Biology has the potential to solve these problems because it can replicate and repair itself, and do a wide variety of chemical reactions including making food, fuel and materials. Synthetic biology can greatly enhance and expand life's evolved repertoire. Using natural and synthetically altered organisms as the feedstock for additive manufacturing could one day make possible the dream of producing bespoke tools, food, smart fabrics and even replacement organs on demand. To this end our lab has produced a proof-of-concept bioprinter with nearly one-cell resolution. Genetically engineering yeast cells to secrete bioproducts subsequent to printing allows the potential to make biomaterials with a fine microstructure. Imagine a production system that, at a few micron scale resolution, can add mollusk shell for compressive strength per unit mass, spider silk or collagen for tensile strength per unit mass, and potentially biologically-deposited wires. Now imagine what new products can be enabled by such a technology, on earth or beyond.

Biology

Biomaterials Out of Thin Air: In Situ, On-Demand Printing of Advanced Biocomposites: A New Materials Design and Production Technique Using 3D-Printed Arrays of Bioengineered Cells

We have completed the proof of concept described in our Phase I proposal, a two-material array of nonstructural proteins. We created an implementation of each step in our technology concept and demonstrated its critical functionality. The biological chassis and printing hardware we created as part of this work can be re-used for future work by inserting a material coding region upstream of the fluorescent tag. Overall, we showed that our technology concept is sound. The mission benefit analyses, as described in our Phase I proposal, are complete and contained in this report. These calculations show that our technology can save hundreds of kilograms of upmass for a potential planetary human habit construction mission: the mass per habitat module can be reduced by approximately one third if the biomaterials are manufactured on Earth and included in the mission upmass, and the full 240 kg per module can be saved if the materials are derived entirely from in situ resources. Mass savings between these two extremes is expected for an actual mission, depending on the level of in situ resource extraction technology. We have shown that continued advancement of this technology concept for use in a space mission environment is justified. Our survey of future development pathways proved extremely informative in light of the lessons learned from our proof of concept work and mission scenario analyses. For example, we were able for the first time to distinguish between the levels of functionality provided by production of structural proteins, other polymers such as polysaccharides, and true organic-inorganic composites such as bone and mineralized shell. This new information represents a significant advance in formulating specific applications, and key enabling technologies, for our proposed concept. We surveyed potential collaborations with other projects and synergies with enabling technologies that are developing. We have received requests for collaboration from other institutions, including labs at Stanford University and Drexel University. We have also received visits from industry, including Organovo, a tissue engineering company, and Autodesk, a major 3D and materials design software company. Finally, we have been in touch with the team behind the 2013 NIAC Phase ll 'Super Ball Bot-Structures for Planetary Landing and Exploration' and are planning to develop our biomaterial printing technology with the goal of enabling tensegrity-based rovers such as theirs to use lighter, more robust materials. A smooth transition from TRL 2 to TRL 3 assumes that the implementations of the technology concept which demonstrate critical functionality are also pathways for future development; while this is the case for most hardware or software projects, the multidisciplinary nature of our project, particularly the biological aspect of it, means that this is not always true. For example, as part of this work we showed that although there are large number of known genetic parts that correspond to non-structural materials, this is not true for sequences for structural organic proteins, let alone biominerals. These realizations allowed us to further subdivide our concept into more detailed development areas, some of which are clearly established at TRL 3, others of which were newly identified sub-technologies moved from TRL 1 to TRL 2. Similarly, although a single feasibility /benefit analysis is sufficient for advancement from TRL 2 to TRL 3, not all potential benefits to a technology concept as broad in scope as ours are apparent at TRL 2. Both our future pathways survey and our proof of concept work highlighted that the true mass savings potential of our technology concept cannot be quantified without modification of existing materials modelling tools to take into account the possibility of positional materials properties customization. Therefore, we have simultaneously both advanced one potential set of applications of our technology concept from TRL 2 to TRL 3 and also identified a previously unknown set of applications and advanced it from TRL 1 to TRL 2. Overall, we have moved the original formulation of our concept forward from TRL 2 to TRL 3, and the expanded formulation of it presented in this document has been advanced from a combination of TRL 1 and early 1RL 2 to an overall late TRL 2. We have also identified the key areas necessary for both short-term and long-term advancement, and made recommendations for specific future work in the most promising directions. With future work on a 1-2 year timeframe to continue advancement to overall TRL 3, we will be well positioned to begin work on a specific space mission technology insertion path.

Biology

JGI Plant Transformation Workshop, May 20-21, 2025

Domestic biomass crops such as sorghum, switchgrass, Miscanthus, and poplar can provide United States industries with renewable feedstocks while also supporting low-input farming systems and strengthening supply chains for biofuels, biochemicals and biomaterials. The U.S. leads globally in biomass crop genomics, yet progress in engineering traits is constrained by slow, genotype-dependent transformation methods and lengthy Design-Build-Test-Learn (DBTL) cycles. At a May 2025 workshop, a panel of experts recommended establishing a DOE Plant Transformation Capability (PTC) to overcome these barriers. The PTC would unite two missions: advancing research to achieve genotype-independent, automated methods, and delivering scalable transformation services through a user-facility model. With expected gains of 10–100x in efficiency, including transformation and cost reduction, the PTC would accelerate the path from discovery to engineered plants, expand community access and training, and support downstream applications and workflows including field trials and regulatory navigation. By enabling rapid and predictable crop engineering, the PTC would strengthen U.S. supply chains, enhance industrial competitiveness, and ensure that DOE’s genomic investments deliver national impact.

09 BIOMASS FUELS

Structure-guided utilization of lignocellulose for catalysis, energy, and biomaterials

As a complex composite of cellulose, hemicellulose, and lignin, plant lignocellulose has long served as a major resource for biomass conversion, materials engineering, and bio-based product development. High-resolution structural insights enabled by solid-state nuclear magnetic resonance (ssNMR) now allow the mapping of polymer interfaces, identification of functional group accessibility, and tracking of molecular organization during processing, all of which are critical factors for optimizing catalytic strategies. These insights could drive transformative progress in lignocellulose-based applications, including selective depolymerization, improved pretreatment design, and efficient upcycling of lignin into resins, plastics, and biomedical materials. In industry-relevant contexts, such as biofuel generation and renewable material manufacturing, understanding the hydration dynamics, cross-linking patterns, and structural heterogeneity is also essential. The ability to visualize these features in native biomass presents a unique opportunity to develop new strategies for sustainability and performance. As the structural toolbox continues to expand, it is becoming a central enabler for innovations in renewable energy, green chemistry, and advanced bioproducts.

bioproduct

Retrobiosynthesis of unnatural lactams via reprogrammed polyketide synthase

Engineered polyketide synthases (PKSs) have great potential as biocatalysts. These unnatural enzymes are capable of synthesizing molecules that are either not amenable to biosynthesis or are extremely challenging to access chemically. PKSs can thus be a powerful platform to expand the chemical landscape beyond the limits of conventional metabolic engineering. Here we employ a retrobiosynthesis approach to design and construct PKSs to produce δ-valerolactam (VL) and three enantiopure α-substituted VL analogues that have no known biosynthetic route. We introduce the engineered PKSs and pathways for various malonyl-CoA derivatives into Pseudomonas putida and use proteomics, metabolomics and culture condition optimization to improve the production of our target compounds. These α-substituted VLs are polymerized into polyamides (nylon-5) or converted into their N-acryloyl derivatives. RAFT polymerization produces bio-derived polymers with potential biomedical applications. Overall, this interdisciplinary effort highlights the versatility and effectiveness of a PKS-based retrobiosynthesis approach in exploring and developing innovative biomaterials.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH

Challenges and Vision for Standardization of Biopolymer Data Sets for Machine Learning

Machine learning (ML) is transforming materials research, yet potential for biopolymer discovery remains constrained by fragmented data and nonstandardized reporting. Biopolymers differ significantly from synthetic polymers, requiring specialized approaches to represent their biosynthetic origins, hierarchical structures, and application-specific metrics. In this Perspective, we identify three core challenges limiting biopolymer representation: information encoding, data quality, and data sharing. We describe the most pressing issues and propose commensurate approaches to address each key challenge. Recommendations include the design and adoption of biopolymer-specific fingerprinting and representation frameworks, development of hybrid human-large language model (LLM) data extraction strategies, and expanding Findable, Accessible, Interoperable, Reusable (FAIR)-compliant repositories. We propose a robust foundation to define interoperable, high-quality data sets that capture the full context of biopolymer materials. Standardized metadata, shared ontologies, and community-driven infrastructure would enable scalable, reproducible workflows and accelerate the ML-driven development of biopolymers.

36 MATERIALS SCIENCE

Leveraging Hydration Forces for Size-Specific Nanoparticle Enrichment with a Redox-Responsive Silica-Binding Elastin-Like Polypeptide

Elastin-like polypeptides (ELPs) are low-complexity proteins that coacervate above a characteristic lower critical solution temperature (LCST). While the thermoresponsiveness of ELPs has been widely exploited in the biomedical and biomaterials fields, their ability to mediate nanoparticle assembly below their transition temperature remains largely unexplored. Here, we show that unmodified ELPs induce the reversible flocculation of silica nanoparticles (SiNPs) by forming backbone hydrogen bonds with surface silanols. Interparticle bridging is modulated by ELP length and concentration and by the presence of N- and C-terminal anchoring groups such as a cysteine residue and a Car9 silica-binding peptide. Using a redox-responsive fusion protein consisting of disulfide-bonded ELP domains terminated by Car9 segments, we stabilize 20 nm SiNPs under oxidizing conditions while triggering particle flocculation upon addition of reductant. We find that SiNP sedimentation under reducing conditions exhibits a sharp dependency on particle size that arises from the curvature-dependent structure of surface silanols. While the isolated silanols of SiNPs smaller than 30 nm are efficiently engaged by the ELP domains of Car9-anchored proteins, repulsion forces associated with the presence of a layer of molecular water together with increased electrostatic repulsion preclude efficient engagement of H-bonded silanols displayed on the surface of SiNPs larger than 60 nm. We harness these findings to selectively enrich SiNPs based on size and expand the concept to titania (TiO2) by demonstrating that rutile nanoparticles can be stabilized or sedimented with solid-binding ELPs by adjusting the solution pH to promote or discourage the formation of a hydration layer. These strategies should prove broadly useful for the separation of other oxides and their polymorphs and provide a tunable strategy for nanoparticle assembly and bioinspired colloidal design.

ELP

Neutrons in Structural Biology: Challenges and Opportunities (Workshop Report)

Gaining a thorough understanding of biological systems requires building our knowledge about biological processes from the level of atoms and electrons, and up to whole organisms. Such comprehensive knowledge will allow for a predictive understanding of complex biological systems behavior. It will guide us in the design and development of novel therapeutics and vaccines to tackle existing health threats and to prepare for future pandemics, and it will provide information necessary to create new biomaterials and bio-inspired technologies through manipulation of biological macromolecules, their assemblies, single cells and even microorganisms. Reaching these goals will require a synergistic combination of multiple experimental techniques with molecular calculations and predictive simulations, and the design and development of new techniques and capabilities that bridge current knowledge and technology gaps. Neutron scattering provides unique information about the biomacromolecular structure and function and can play a major role in achieving these goals. A workshop was held to engage the scientific community in identifying pressing challenges in biochemistry, structural biology, enzymology and structure-guided drug design not solved with the current neutron scattering technologies or utilizing other structural biology techniques such as X-ray crystallography, NMR, and cryo-EM. The workshop brought together structural biology, biochemistry and computational experts, as well as early career researchers and students, creating a forum for discussing scientific advancement and collaboration. The workshop included a one-day satellite training workshop where graduate students and postdoctoral researchers were educated in the application of neutron crystallography and small-angle scattering in structural biology. Furthermore, the Instrument Scientific Advisory Board (ISAB) for the development of a macromolecular neutron diffractometer at ORNL’s Second Target Station was introduced at the workshop. The major outcome was that neutrons can provide atomic-level understanding of biomacromolecular structure, function and dynamics which is of paramount importance for addressing the identified challenges. Neutron crystallography, in particular, can resolve long-standing biochemical issues regarding enzyme function by delineating the underlying chemistry and can have a major impact on the design of small-molecule therapeutics, especially in combination with molecular computation (quantum chemistry and molecular dynamics simulations) and the emerging artificial intelligence (AI)-assisted drug design technologies. The unique properties of neutrons, including their high sensitivity to hydrogen and their non-destructive nature, make them ideal probes of biological matter. There is a palpable need in the scientific community to expand and enhance the impact of neutron sciences on biology. Neutron crystallography is the only structural biology method capable of determining positions of all hydrogen atoms in proteins, nucleic acids and their complexes at near-physiological temperatures and of unstable species at cryogenic temperatures. Moreover, neutron analysis is non-ionizing, non-destructive and does not perturb the structure or redox chemistry of active site metal centers and clusters in proteins, which can be invaluable for studying radiation-sensitive metalloprotein complexes. Further, neutron energies used in scattering applications are similar to atomic motions, permitting neutron spectroscopies to characterize the dynamics of biomacromolecules on the picosecond to microsecond timescales. The different sensitivities of neutrons to protium (H) and deuterium (D) isotopes of hydrogen allow enhanced visibility of specific parts of biological complexes through isotopic labeling. The impact of neutrons will be most powerful when neutron scattering is combined with complementary experimental techniques that use photons and electrons, and with high-performance computing. The interconnection and mutuality of the experimental and theoretical capabilities will drive discoveries in biological and health sciences to generate more complete picture of complex biological systems. The major limitation in the field of biological neutron crystallography has been signal-to-noise, demanding large samples that are difficult to produce for the majority of biomacromolecules and limiting the applicability of this technique in biological sciences. A neutron crystallography instrument at the Second Target Station will revolutionize biological science with neutrons by engaging a large scientific community of structural biologists, enabling successful neutron diffraction experiments from radically smaller biomacromolecular crystals, resolving unanswered biochemical questions, and meaningfully contributing to rational drug design. The meeting highlighted 10 grand challenges that will be addressed with this advanced capability over the next decade and beyond, and the recommendations required to help address them are given below.

59 BASIC BIOLOGICAL SCIENCES