Geometric classifications of 3D pores are useful for studying relationships between pore geometry and function in granular materials. Pores are typically characterized by size, but size alone cannot explain 3D phenomena like transport. Here, we implement a KNN-based pore classification approach emphasizing shape-related properties. We find pore types produced in randomly packed systems resemble those of ideal, hexagonally packed systems. In both random and perfect systems, pores tend to configure as octahedrons (O's) and icosahedrons (I's). We demonstrate the physical implications of this by running flow simulations through a granular system and observe differences in fluid dynamic behaviors between pore types. We finally show the O/I pore distribution can be tuned by modifying particle properties (shape, stiffness, size). Overall, this work enables analysis of granular system behaviors by 3D pore shape and informs system design for desired distributions of pore geometries.

Inflammatory bowel disease (IBD) is a chronic and increasingly prevalent gastrointestinal disorder that remains difficult to treat due to the limited efficacy of conventional therapies, often compromised by premature drug release and systemic side effects. Stimuli-responsive nanomaterials have emerged as a promising solution, enabling targeted and controlled drug delivery at inflamed sites to enhance therapeutic outcomes and reduce toxicity. This review systematically examines the recent development and application of these smart nanomaterial drug-delivery systems for IBD therapy over the past years. By responding to the unique pathological features of the IBD microenvironment, these systems enable improved drug targeting and site-specific release. Despite significant progress, challenges such as scalable manufacturing, long-term safety, and clinical translation remain. Future research may focus on reducing batch-to-batch variation, conducting comprehensive safety assessments, and integrating personalized medicine approaches to fully harness the potential of stimuli-responsive nanomaterials in IBD treatment.

Current 4D materials typically rely on external stimuli such as heat or light to accomplish changes in shape, limiting the biocompatibility of these materials. Here, a composite bioink consisting of oxidized and methacrylated alginate (OMA), methacrylated gelatin (GelMA), and gelatin microspheres is developed to accomplish free-standing 4D bioprinting of cell-laden structures driven by an internal stimulus: cell-contractile forces (CCFs). 4D changes in shape are directed by forming bilayer constructs consisting of one cell-free and one cell-laden layer. Human mesenchymal stem cells (hMSCs) are encapsulated to demonstrate the ability to simultaneously induce changes in shape and chondrogenic/osteogenic differentiation. Finally, the capability to pattern each layer of the printed constructs is exhibited to obtain complex geometric changes, including bending around two separate, non-parallel axes. Bioprinting of such 4D constructs mediated by CCFs empowers the formation of more complex constructs, contributing to a greater degree of biomimicry of biological 4D phenomena.

While developing new polymers typically requires years of investigation, blending existing polymers offers a cost-effective strategy to create new materials. However, developing functional polymer blends is often a slow and challenging process due to their vast design space, the non-additive nature of polymer properties, and limited fundamental understanding to guide the optimization. Here, we report an autonomous platform that addresses these challenges by integrating high-throughput blending, real-time data acquisition, and an evolutionary algorithm for composition optimization. This approach enables rapid exploration of complex combinatorial blending spaces of random heteropolymers (RHPs). With enzyme thermal stability as a model objective, this system discovered random heteropolymer blends (RHPBs) that outperform all constituents. Retrospective analysis reveals segment-level interactions correlated with the performance. This work highlights the opportunity for materials discovery within the RHP and RHPB space and the immense potential of leveraging autonomous discovery platforms to accelerate the discovery of polymers with emergent properties.

Increased adhesion forces between trabecular meshwork (TM) cells and the extracellular matrix (ECM) in the human outflow pathway are associated with elevated intraocular pressure (IOP), a key risk factor for primary open-angle glaucoma (POAG). This study examined how matrix stiffness affects traction forces and collagen fibril organization in normal and glaucomatous TM cells using collagen gels with stiffness levels of 4.7 and 27.7 kPa. Normal high-flow (HF) TM/JCT cells showed greater traction forces on the stiffer gels, whereas glaucomatous HF TM/JCT cells generated greater forces on the softer gels. These differences correlated with findings that normal cells are ~1.6-fold stiffer than their glaucomatous counterparts. Glaucomatous cells also exhibited anisotropic collagen fibril alignment and distinct cytoskeletal dynamics. These results suggest that altered mechanosensitivity and ECM reorganization in glaucomatous TM cells may contribute to promoting ECM stiffening, elevated IOP, and disease progression, highlighting potential therapeutic strategies.

The threat of future coronavirus pandemics requires developing effective vaccine technologies that provide broad and long-lasting protection against circulating and emerging strains. Here we report a multivalent liposomal hydrogel vaccine technology comprising the receptor binding domain (RBD) of up to four SARS and MERS coronavirus strains non-covalently displayed on the surface of the liposomes within the hydrogel structure. The multivalent presentation and sustained exposure of RBD antigens improved the potency, neutralizing activity, durability, and consistency of antibody responses across homologous and heterologous coronavirus strains in a naïve murine model. When administrated in animals pre-exposed to wild-type SARS-CoV-2 antigens, liposomal hydrogels elicited durable antibody responses against the homologous SARS and MERS strains for over six months and elicited neutralizing activity against the immune-evasive SARS-CoV-2 variant Omicron BA.4/BA.5. Overall, the tunable liposomal hydrogel platform we report here generates robust responses against diverse coronaviruses, supporting global efforts to respond to future viral outbreaks.

Natural plants provide a wealth of valuable materials for healthcare, with much of their potential often overlooked in what is commonly considered waste. This study focuses on the (), whose fruit, (PDH), has long been used in traditional Chinese medicine. By investigating PDH husk's swelling behavior, we efficiently extracted its polysaccharides without harsh chemicals. Using micro-compression, we developed a viscoelastic hydrogel, and through electrostatic crosslinking with chitosan, we further enhanced its mechanical properties. The hydrogel exhibited biocompatibility and accelerated wound healing by promoting keratinocyte migration. Additionally, it outperformed commercial patches as a skin-attached interfacial material for electrocardiography (ECG), demonstrating superior signal-to-noise ratios. Integrated into a 16-channel mesh-electronic device, the hydrogel provided stable performance for epicardial ECG recording on a beating heart. This research highlights the potential of rigid polysaccharide waste, presenting a sustainable approach to converting plant waste into valuable healthcare materials.

The acute inflammatory response is an inherent protective mechanism, its unsuccessful resolution can contribute to disease pathogenesis and potentially lead to death. Innate immune cells are the first line of host defenders and play a substantial role in inflammation initiation, amplification, resolution, or subsequent disease progression. As the resolution of inflammation is an active and highly regulated process, modulating innate immune cells, including neutrophils, monocytes and macrophages, and endothelial cells, and their interactions offer opportunities to control excessive inflammation. Nanobiomaterials have shown superior therapeutic potential in inflammation-related diseases by manipulating inflammatory responses because nanobiomaterials can target and interact with innate immune cells. Versatile nanobiomaterials can be designed for targeted modulation of specific innate immune responses. Nanopro-resolving medicines have been prepared both with pro-resolving lipid mediators and peptides each demonstrated to active resolution of inflammation in animal disease models. Here, we review innovative nanobiomaterials for modulating innate immunity and alleviating inflammation. We summarise the strategies converging the design of nanobiomaterials and the nano-bio interaction in modulating innate immune profiles and propelling the advancement of nanobiomaterials for inflammatory disease treatments. We also propose the future perspectives and translational challenges of nanobiomaterials that need to be overcome in this swiftly rising field.

Mesenchymal stem cell (MSC) stands as a prominent choice in regenerative medicine, yet their therapeutic potential remains controversial due to challenges in maintaining lineage and viability. As directly injected MSCs are quickly cleared by the host immune system, entrapping viable cells in a 3D semi-permeable hydrogel matrix extends cell retention, showing great promise in enhancing therapeutic effect. However, the effects of hydrogel encapsulation on MSC subpopulations are not fully understood. Here, we fabricate thin-shell alginate hydrogel microcapsules using droplet microfluidics, controlling the shell mechanical properties by adjusting alginate molecular weight. We find that a stiffer shell increases the proliferation and supports the residence of MSCs in vivo than a softer shell. The stiff 3D hydrogel also promotes the maintenance of stemness, as confirmed by single-cell RNA sequencing. Our work demonstrates the potential of hydrogel-encapsulated stem cells for long-term therapeutic applications, offering insight into modulating MSC subpopulations for specific function.

Bacterial synthetic multicellular systems are promising platforms for engineered living materials (ELMs) for medical, biosynthesis, environmental, and smart materials applications. Recent advancements in genetically encoded adhesion toolkits have enabled precise manipulation of cell-cell adhesion and the design and patterning of self-assembled multicellular materials. However, in contrast to gene regulation in synthetic biology, the characterization and control of synthetic adhesins remains limited. Here, we demonstrate the quantitative characterization of a bacterial synthetic adhesion toolbox through various biophysical methods. We determine key parameters, including number of adhesins per cell, in-membrane diffusion constant, production and decay rates, and bond-breaking force between adhesins. With these parameters, we demonstrate the bottom-up prediction and quantitative tuning of macroscopic ELM properties (tensile strength) and, furthermore, that cells inside ELMs are connected only by a small fraction of available adhesins. These results enable the rational engineering, characterization, and modeling of other synthetic and natural adhesins and multicellular consortia.

Tissue engineering has long sought to rapidly generate perfusable vascularized tissues with vessel sizes spanning those seen in humans. Current techniques such as biological 3D printing (top-down) and cellular self-assembly (bottom-up) are resource intensive and have not overcome the inherent tradeoff between vessel resolution and assembly time, limiting their utility and scalability for engineering tissues. We present a flexible and scalable technique termed SPAN - acrificial ercolation of nisotropic etworks, where a network of perfusable channels is created throughout a tissue in minutes, irrespective of its size. Conduits with length scales spanning arterioles to capillaries are generated using pipettable alginate fibers that interconnect above a percolation density threshold and are then degraded within constructs of arbitrary size and shape. SPAN is readily used within common tissue engineering processes, can be used to generate endothelial cell-lined vasculature in a multi-cell type construct, and paves the way for rapid assembly of perfusable tissues.

[This corrects the article PMC7442115.].

Currently, there is no mechanistic model that fully explains the initial synthesis and organization of durable animal structure. As a result, our understanding of extracellular matrix (ECM) development and pathologies (e.g., persistent fibrosis) remains limited. Here, we identify and characterize cell-generated mechanical strains that direct the assembly of the ECM. Cell kinematics comprise cooperative retrograde "pulls" that organize and precipitate biopolymer structure along lines of tension. High-resolution optical microscopy revealed five unique classes of retrograde "pulls" that result in the production of filaments. Live-cell confocal imaging confirmed that retrograde pulls can directly cause the formation of fibronectin filaments that then colocalize with collagen aggregates exported from the cell, producing persistent elongated structures aligned with the direction of the tension. The findings suggest a new model for initial durable structure formation in animals. The results have important implications for ECM development and growth and life-threatening pathologies of the ECM, such as fibrosis.

There is a growing interest in the development of technologies to probe and direct in vitro cellular function for fundamental organoid and stem cell biology, functional tissue and metabolic engineering, and biotherapeutic formulation. Recapitulating many critical aspects of the native cellular niche, hydrogel biomaterials have proven to be a defining platform technology in this space, catapulting biological investigation from traditional two-dimensional (2D) culture into the 3D world. Seeking to better emulate the dynamic heterogeneity characteristic of all living tissues, global efforts over the last several years have centered around upgrading hydrogel design from relatively simple and static architectures into stimuli-responsive and spatiotemporally evolvable niches. Towards this end, advances from traditionally disparate fields including bioorthogonal click chemistry, chemoenzymatic synthesis, and DNA nanotechnology have been co-opted and integrated to construct 4D-tunable systems that undergo preprogrammed functional changes in response to user-defined inputs. In this Review, we highlight how advances in synthetic, semisynthetic, and bio-based chemistries have played a critical role in the triggered creation and customization of next-generation hydrogel biomaterials. We also chart how these advances stand to energize the translational pipeline of hydrogels from bench to market and close with an outlook on outstanding opportunities and challenges that lay ahead.

The ability of endothelial cells to sense and respond to dynamic changes in blood flow is critical for vascular homeostasis and cardiovascular health. The mechanical and geometric properties of the nuclear and cytoplasmic compartments affect mechanotransduction. We hypothesized that alterations to these parameters have resulting mechanosensory consequences. Using atomic force microscopy and mathematical modeling, we assessed how the nuclear and cytoplasmic compartment stiffnesses modulate shear stress transfer to the nucleus within aging endothelial cells. Our computational studies revealed that the critical parameter controlling shear transfer is not the individual mechanics of these compartments, but the stiffness ratio between them. Replicatively aged cells had a reduced stiffness ratio, attenuating shear transfer, while the ratio was not altered in a genetic model of accelerated aging. We provide a theoretical framework suggesting that dysregulation of the shear stress response can be uniquely imparted by relative mechanical changes in subcellular compartments.

[This corrects the article DOI: 10.1016/j.matt.2021.09.022.].

Cell mechanics are determined by an intracellular biopolymer network, including intermediate filaments that are expressed in a cell-type-specific manner. A prominent pair of intermediate filaments are keratin and vimentin, as they are expressed by non-motile and motile cells, respectively. Therefore, the differential expression of these proteins coincides with a change in cellular mechanics and dynamic properties of the cells. This observation raises the question of how the mechanical properties already differ on the single filament level. Here, we use optical tweezers and a computational model to compare the stretching and dissipation behavior of the two filament types. We find that keratin and vimentin filaments behave in opposite ways: keratin filaments elongate but retain their stiffness, whereas vimentin filaments soften but retain their length. This finding is explained by fundamentally different ways to dissipate energy: viscous sliding of subunits within keratin filaments and non-equilibrium α helix unfolding in vimentin filaments.

Nanomedicines have transformed promising therapeutic agents into clinically approved medicines with optimal safety and efficacy profiles. This is exemplified by the mRNA vaccines against COVID-19, which were made possible by lipid nanoparticle technology. Despite the success of nanomedicines to date, their design remains far from trivial, in part due to the complexity associated with their preclinical development. Herein, we propose a nanomedicine materials acceleration platform (NanoMAP) to streamline the preclinical development of these formulations. NanoMAP combines high-throughput experimentation with state-of-the-art advances in artificial intelligence (including active learning and few-shot learning) as well as a web-based application for data sharing. The deployment of NanoMAP requires interdisciplinary collaboration between leading figures in drug delivery and artificial intelligence to enable this data-driven design approach. The proposed approach will not only expedite the development of next-generation nanomedicines but also encourage participation of the pharmaceutical science community in a large data curation initiative.

Coronaviruses have historically precipitated global pandemics of severe acute respiratory syndrome (SARS) into devastating public health crises. Despite the virus's rapid rate of mutation, all SARS coronavirus 2 (SARS-CoV-2) variants are known to gain entry into host cells primarily through complexation with angiotensin-converting enzyme 2 (ACE2). Although ACE2 has potential as a druggable decoy to block viral entry, its clinical use is complicated by its essential biological role as a carboxypeptidase and hindered by its structural and chemical instability. Here we designed supramolecular filaments, called fACE2, that can silence ACE2's enzymatic activity and immobilize ACE2 to their surface through enzyme-substrate complexation. This docking strategy enables ACE2 to be effectively delivered in inhalable aerosols and improves its structural stability and functional preservation. fACE2 exhibits enhanced and prolonged inhibition of viral entry compared with ACE2 alone while mitigating lung injury .

Slippery surfaces are sought after due to their wide range of applications in self-cleaning, drag reduction, fouling-resistance, enhanced condensation, biomedical implants etc. Recently, non-textured, all-solid, slippery surfaces have gained significant attention because of their advantages over super-repellent surfaces and lubricant-infused surfaces. Currently, almost all non-textured, all-solid, slippery surfaces are hydrophobic. In this work, we elucidate the systematic design of non-textured, all-solid, slippery hydrophilic (SLIC) surfaces by covalently grafting polyethylene glycol (PEG) brushes to smooth substrates. Furthermore, we postulate a plateau in slipperiness above a critical grafting density, which occurs when the tethered brush size is equal to the inter-tether distance. Our SLIC surfaces demonstrate exceptional performance in condensation and fouling-resistance compared to non-slippery hydrophilic surfaces and slippery hydrophobic surfaces. Based on these results, SLIC surfaces constitute an emerging class of surfaces with the potential to benefit multiple technological landscapes ranging from thermofluidics to biofluidics.

Recently, the potential to create functional materials from various forms of organic matter has received increased interest due to its potential to address environmental concerns. However, the process of creating novel materials from biomass requires extensive experimentation. A promising means of predicting the properties of such materials would be the use of machine-learning models trained on or integrated into self-learned experimental data and methods. We outline an automated system for the discovery and characterization of novel, sustainable, and functional materials from input biomass. Artificial intelligence provides the capacity to examine experimental data, draw connections between composite composition and behavior, and design future experiments to expand the system's understanding of the studied materials. Extensions to the system are described that could further accelerate the discovery of sustainable composites, including the use of interpretable machine-learning methods to expand the insights gleaned from to human-readable materiomic insights about material process-structure-functional relationships.