Noah Eckman

All Publications

• Enabling global access to potent subunit vaccines with a simple and scalable injectable hydrogel platform. Biomaterials science Ganesh, P., Prossnitz, A. N., Jons, C. K., Eckman, N., Alakesh, A., Song, Y. E., Sen, S., Appel, E. A. 2025

  Abstract

  Vaccines have been crucial to dramatic improvements in global health in recent decades, yet next-generation vaccine technologies remain out of reach for much of the world. In particular, there are two overarching global needs: (i) develop vaccines eliciting more potent and durable immune responses, especially to reduce incidence of highly communicable diseases, and (ii) enable simple and cost-efficient formulation to maximize global access. Here, we develop an injectable hydrogel depot technology prepared through physical mixing of commercially available, generally recognized as safe (GRAS) polymers that can be formulated with subunit vaccine components to improve immune responses compared to standard vaccine formulations. We demonstrate that these hydrogels are shear-thinning and rapidly self-healing, enabling facile administration via injection, and they exhibit high yield stresses required for robust in vivo depot formation post-injection. These rheological properties prolong release of subunit vaccine cargo over a period of weeks, both in vitro and in vivo, and synchronize release kinetics across physicochemically distinct vaccine components (antigens and adjuvants). When used for formulation of subunit vaccines against wild-type SARS-CoV-2 and H5N1 influenza, these hydrogels enhance potency and durability of immune responses. This vaccine formulation technology can improve protection against current and potential future pandemic pathogens.

  View details for DOI 10.1039/d5bm01131k

  View details for PubMedID 41190921

• Hydrogel formulations for sustained-release of broadly neutralizing antibodies. Journal of controlled release : official journal of the Controlled Release Society Jons, C. K., Kasse, C. M., Mayer, B. T., Hyrien, O., Sen, S., Meany, E. L., d'Aquino, A. I., Ganesh, P., Eckman, N., Dong, C., Yan, J., Nguyen, L. T., Doulames, V. M., Song, Y. E., Saouaf, O. M., Williams, C. M., Williams, S. C., Paredes, J., Raghavan, R., Palomares, M., Alpert, M., Yates, N. L., Tomaras, G. D., Seaman, M. S., Farzan, M., Appel, E. A. 2025: 114349

  Abstract

  Sustained serum levels of broadly neutralizing antibodies (bnAbs) are crucial for effective passive immunization against infectious diseases as protection persists only while these bnAbs remain at adequate concentrations within the body. Current obstacles, such as poor pharmacokinetics (PK) and burdensome administration, must be overcome to make bnAbs a viable option for pre- and post-exposure prophylaxis. In this work, we explore how a polymer-nanoparticle (PNP) hydrogel depot technology can be engineered to prolong protein delivery and enable drug exposure on the order of weeks to months. In-vivo studies in mice and rats demonstrate extended protein release compared to bolus administration, and modeling efforts predict the impact of both the elimination half-life of the active pharmaceutical ingredient and hydrogel depot volume on overall pharmacokinetics. Moreover, flow cytometry characterization reveals that immune cell infiltration into the hydrogel depot can result in faster-than-expected release of antibody cargo on account of active transport via cellular uptake. We then demonstrate that co-formulation of antibodies with an anti-inflammatory agent reduces cellular infiltration and resulting active transport, further extending delivery and pharmacokinetics. Finally, multicompartmental modeling predicts the human PK profiles of clinically relevant HIV bnAbs delivered via subcutaneous hydrogel injection. These findings aid in the development of next generation hydrogel materials that stabilize and slowly release bnAbs for long-term pre-exposure immunoprophylaxis.

  View details for DOI 10.1016/j.jconrel.2025.114349

  View details for PubMedID 41177463

• Intranasal Sertraline for the Investigation of Nose-to-Brain Delivery to Mitigate Systemic Exposure. ACS pharmacology & translational science Williams, S. C., Lantz, T., Doulames, V., Alakesh, A., Ramos Mejia, D., Jons, C. K., Huang, Z. Y., Eckman, N., Appel, E. A. 2025; 8 (10): 3669-3676

  Abstract

  Antenatal depression, or depression during pregnancy, is a common psychiatric disorder and poses significant risks to both the mother and the fetus. Despite these risks, it is frequently left untreated due to fears of side effects caused by antidepressant medications which cross through the placental barrier. It is therefore desirable to develop formulation strategies to mitigate systemic exposure to psychotropics while maintaining their efficacy. In this work, we develop formulations of sertraline, a common antidepressant, to target delivery to the brain through intranasal administration. Formulation engineering enables successful solubilization of sertraline at high concentrations over months at room temperature. Using mice, we compare sertraline biodistribution following intranasal administration and standard oral administration. Intranasal administration of our candidate formulation provides comparable brain exposure at half the dose compared to oral treatment and lowers the maximum plasma exposure. These findings suggest that intranasal administration may provide selectivity for drug exposure in the central nervous system over systemic exposure.

  View details for DOI 10.1021/acsptsci.5c00560

  View details for PubMedID 41098574

  View details for PubMedCentralID PMC12519257

• Ultrahigh-concentration biologic therapeutics enabled by spray drying with a glassy surfactant excipient. Science translational medicine Jons, C. K., Prossnitz, A. N., Eckman, N., Dong, C., Utz, A., Appel, E. A. 2025; 17 (812): eadv6427

  Abstract

  Biopharmaceuticals such as peptides and antibodies have become critical to health care. Despite their exceptional potency and specificity, biopharmaceuticals are prone to aggregation, which can limit efficacy. These therapies therefore often require low-concentration formulations as well as cold storage to maintain stability; however, high doses are required to treat many diseases. Most approved protein drug products are administered intravenously, imposing excessive burdens on patients. New approaches are needed to formulate proteins at high concentrations to enable less burdensome subcutaneous injection, preferably with an autoinjector that can be used directly by patients. To address this challenge, we report a subcutaneously injectable protein delivery platform composed of spray-dried protein microparticles suspended in a nonsolvent liquid carrier. These microparticles contain only biopharmaceuticals and a high-glass transition temperature polyacrylamide-derived copolymer excipient that affords key benefits over traditional excipients. First, the excipient improved stabilization of biopharmaceuticals through the spray-drying process, and second, it improved morphology and properties of the spray-dried particles, enhancing suspension injectability. We demonstrated with albumin, human immunoglobulin G, and an anti-COVID monoclonal antibody (IDBiologics) that this technology enables ultrahigh-concentration protein formulations (exceeding 500 milligrams per milliliter) that are injectable through standard needles with clinically relevant injection forces. In addition, experiments with two clinically relevant antibody drugs show that these ultrahigh-concentration formulations reduce required injection volumes without altering pharmacokinetics or efficacy in mice. This approach could nearly triple the number of commercial protein drugs amenable to subcutaneous administration, improving access to these critical biopharmaceuticals.

  View details for DOI 10.1126/scitranslmed.adv6427

  View details for PubMedID 40834101

• Crosslink Dynamics Control Injection Force and Flow Profiles of Non-Covalent Gels MACROMOLECULES Eckman, N., Appel, E. A. 2025

  View details for DOI 10.1021/acs.macromol.5c00854

  View details for Web of Science ID 001503523200001

• Generation of an inflammatory niche in a hydrogel depot through recruitment of key immune cells improves efficacy of mRNA vaccines. Science advances Meany, E. L., Klich, J. H., Jons, C. K., Mao, T., Chaudhary, N., Utz, A., Baillet, J., Song, Y. E., Saouaf, O. M., Ou, B. S., Williams, S. C., Eckman, N., Irvine, D. J., Appel, E. 2025; 11 (15): eadr2631

  Abstract

  Messenger RNA (mRNA) delivered in lipid nanoparticles (LNPs) rose to the forefront of vaccine candidates during the COVID-19 pandemic due to scalability, adaptability, and potency. Yet, there remain critical areas for improvements of these vaccines in durability and breadth of humoral responses. In this work, we explore a modular strategy to target mRNA/LNPs to antigen-presenting cells with an injectable polymer-nanoparticle (PNP) hydrogel technology, which recruits key immune cells and forms an immunological niche in vivo. We characterize this niche on a single-cell level and find it is highly tunable through incorporation of adjuvants like MPLAs and 3M-052. Delivering commercially available severe acute respiratory syndrome coronavirus 2 mRNA vaccines in PNP hydrogels improves the durability and quality of germinal center reactions, and the magnitude, breadth, and durability of humoral responses. The tunable immune niche formed within PNP hydrogels effectively skews immune responses based on encapsulated adjuvants, creating opportunities to precisely modulate mRNA/LNP vaccines for various indications from infectious diseases to cancers.

  View details for DOI 10.1126/sciadv.adr2631

  View details for PubMedID 40215318

  View details for PubMedCentralID PMC11988412

• Highly Extensible Physically Crosslinked Hydrogels for High-Speed 3D Bioprinting. Advanced healthcare materials Song, Y. E., Eckman, N., Sen, S., Jons, C. K., Saouaf, O. M., Appel, E. A. 2025: e2404988

  Abstract

  Hydrogels have emerged as promising materials for bioprinting and many other biomedical applications due to their high degree of biocompatibility and ability to support and/or modulate cell viability and function. Yet, many hydrogel bioinks have suffered from low efficiency due to limitations on accessible printing speeds, often limiting cell viability and/or the constructs which can be generated. In this study, a highly extensible bioink system created by modulating the rheology of physically crosslinked hydrogels comprising hydrophobically-modified cellulosics and either surfactants or cyclodextrins is reported. It is demonstrated that these hydrogels are highly shear-thinning with broadly tunable viscoelasticity and stress-relaxation through simple modulation of the composition. Rheological experiments demonstrate that increasing concentration of rheology-modifying additives yields hydrogel materials exhibiting extensional strain-to-break values up to 2000%, which is amongst the most extensible examples of physically crosslinked hydrogels of this type. The potential of these hydrogels for use as bioinks is demonstrated by evaluating the relationship between extensibility and printability, demonstrating that greater hydrogel extensibility enables faster print speeds and smaller print features. The findings suggest that optimizing hydrogel extensibility can enhance high-speed 3D bioprinting capabilities, reporting over 5000 fold enhancement in speed index compared to existing works reported for hydrogel-based bioinks in extrusion-based printing.

  View details for DOI 10.1002/adhm.202404988

  View details for PubMedID 39955737

• Crosslink strength governs yielding behavior in dynamically crosslinked hydrogels. Biomaterials science Eckman, N., Grosskopf, A. K., Jiang, G., Kamani, K., Huang, M. S., Schmittlein, B., Heilshorn, S. C., Rogers, S., Appel, E. A. 2025

  Abstract

  Yielding of dynamically crosslinked hydrogels, or the transition between a solid-like and liquid-like state, allows facile injection and utility in translational biomedical applications including delivery of therapeutic cells. Unfortunately, the time-varying nature of the transition is not well understood, nor are there design rules for understanding the effects of yielding on encapsulated cells. Here, we unveil underlying molecular mechanisms governing the yielding transition of dynamically crosslinked gels currently being researched for use in cell therapy. We demonstrate through nonlinear rheological characterization that the network dynamics of the dynamic hydrogels dictate the speed and character of their yielding transition. Rheological testing of these materials reveals unexpected elastic strain stiffening during yielding, as well as characterization of the rapidity of the yielding transition. A slower yielding speed explains enhanced protection of directly injected cells from shear forces, highlighting the importance of mechanical characterization of all phases of yield-stress biomaterials.

  View details for DOI 10.1039/d4bm01323a

  View details for PubMedID 39912428

• A thiol-ene click-based strategy to customize injectable polymer-nanoparticle hydrogel properties for therapeutic delivery. Biomaterials science Bailey, S. J., Eckman, N., Brunel, E. S., Jons, C. K., Sen, S., Appel, E. A. 2025

  Abstract

  Polymer-nanoparticle (PNP) hydrogels are a promising injectable biomaterial platform that has been used for a wide range of biomedical applications including adhesion prevention, adoptive cell delivery, and controlled drug release. By tuning the chemical, mechanical, and erosion properties of injected hydrogel depots, additional control over cell compatibility and pharmaceutical release kinetics may be realized. Here, we employ thiol-ene click chemistry to prepare a library of modified hydroxypropylmethylcellulose (HPMC) derivatives for subsequent use in PNP hydrogel applications. When combined with poly(ethylene glycol)-b-poly(lactic acid) nanoparticles, we demonstrate that systematically altering the hydrophobic, steric, or pi stacking character of HPMC modifications can readily tailor the mechanical properties of PNP hydrogels. Additionally, we highlight the compatibility of the synthetic platform for the incorporation of cysteine-bearing peptides to access PNP hydrogels with improved bioactivity. Finally, through leveraging the tunable physical properties afforded by this method, we show hydrogel retention time in vivo can be dramatically altered without sacrificing mesh size or cargo diffusion rates. This work offers a route to optimize PNP hydrogels for a variety of translational applications and holds promise in the highly tunable delivery of pharmaceuticals and adoptive cells.

  View details for DOI 10.1039/d4bm01315h

  View details for PubMedID 39898598

  View details for PubMedCentralID PMC11789556

• Clonally expanded, targetable, natural killer-like NKG7 T cells seed the aged spinal cord to disrupt myeloid-dependent wound healing. Neuron Kong, G., Song, Y., Yan, Y., Calderazzo, S. M., Saddala, M. S., De Labastida Rivera, F., Cherry, J. D., Eckman, N., Appel, E. A., Velenosi, A., Swarup, V., Kawaguchi, R., Ng, S. S., Kwon, B. K., Gate, D., Engwerda, C. R., Zhou, L., Di Giovanni, S. 2025

  Abstract

  Spinal cord injury (SCI) increasingly affects aged individuals, where functional impairment and mortality are highest. However, the aging-dependent mechanisms underpinning tissue damage remain elusive. Here, we find that natural killer-like T (NKLT) cells seed the intact aged human and murine spinal cord and multiply further after injury. NKLT cells accumulate in the spinal cord via C-X-C motif chemokine receptor 6 and ligand 16 signaling to clonally expand by engaging with major histocompatibility complex (MHC)-I-expressing myeloid cells. NKLT cells expressing natural killer cell granule protein 7 (Nkg7) disrupt myeloid-cell-dependent wound healing in the aged injured cord. Nkg7 deletion in mice curbs NKLT cell degranulation to normalize the myeloid cell phenotype, thus promoting tissue repair and axonal integrity. Monoclonal antibodies neutralizing CD8+ T cells after SCI enhance neurological recovery by promoting wound healing. Our results unveil a reversible role for NKG7+CD8+ NKLT cells in exacerbating tissue damage, suggesting a clinically relevant treatment for SCI.

  View details for DOI 10.1016/j.neuron.2024.12.012

  View details for PubMedID 39809279

• Defining Structure-Function Relationships of Amphiphilic Excipients Enables Rational Design of Ultra-Stable Biopharmaceuticals. Advanced science (Weinheim, Baden-Wurttemberg, Germany) Prossnitz, A. N., Nguyen, L. T., Eckman, N., Borkar, S., Tetef, S., Autzen, A. A., Fuller, G. G., Appel, E. A. 2025: e2409604

  Abstract

  Biopharmaceuticals are the fastest-growing class of drugs in the healthcare industry, but their global reach is severely limited by their propensity for rapid aggregation. Currently, surfactant excipients such as polysorbates and poloxamers are used to prevent protein aggregation, which significantly extends shelf-life. Unfortunately, these excipients are themselves unstable, oxidizing rapidly into 100s of distinct compounds, some of which cause severe adverse events in patients. Here, the highly stable, well-defined, and modular nature of amphiphilic polyacrylamide-derived excipients is leveraged to isolate the key mechanisms responsible for excipient-mediated protein stabilization. With a library of compositionally identical but structurally distinct amphiphilic excipients, a new property is quantified, compositional dispersity, that is key to excipient performance and utilized this property to rationally design new ultra-stable surfactant excipients that increase the stability of a notoriously unstable biopharmaceutical, monomeric insulin, by an order of magnitude. This comprehensive and generalizable understanding of excipient structure-function relationships represents a paradigm shift for the formulation of biopharmaceuticals, moving away from trial-and-error screening approaches toward rational design.

  View details for DOI 10.1002/advs.202409604

  View details for PubMedID 39764759

• RGD-Modified Hydrogel Maintains Cell Growth in Mechanically-Induced Limbal Stem Cell Deficient Mouse Model Esmaeilkhanian, H., Swarup, A., Eckman, N., Dhowre, H., Ercal, O., Shadmani, A., Appel, E., Wu, A. Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2024

  View details for Web of Science ID 001312227700127

• Biomaterials to enhance adoptive cell therapy NATURE REVIEWS BIOENGINEERING Eckman, N., Nejatfard, A., Cavet, R., Grosskopf, A. K., Appel, E. A. 2024; 2 (5): 408-424

  View details for DOI 10.1038/s44222-023-00148-z

  View details for Web of Science ID 001390098900004

• Label-Free Composition Analysis of Supramolecular Polymer-Nanoparticle Hydrogels by Reversed-Phase Liquid Chromatography Coupled with a Charged Aerosol Detector. Analytical chemistry Tang, S., Pederson, Z., Meany, E. L., Yen, C., Swansiger, A. K., Prell, J. S., Chen, B., Grosskopf, A. K., Eckman, N., Jiang, G., Baillet, J., Pellett, J. D., Appel, E. A. 2024

  Abstract

  Supramolecular hydrogels formed through polymer-nanoparticle interactions are promising biocompatible materials for translational medicines. This class of hydrogels exhibits shear-thinning behavior and rapid recovery of mechanical properties, providing desirable attributes for formulating sprayable and injectable therapeutics. Characterization of hydrogel composition and loading of encapsulated drugs is critical to achieving the desired rheological behavior as well as tunable in vitro and in vivo payload release kinetics. However, quantitation of hydrogel composition is challenging due to material complexity, heterogeneity, high molecular weight, and the lack of chromophores. Here, we present a label-free approach to simultaneously determine hydrogel polymeric components and encapsulated payloads by coupling a reversed phase liquid chromatographic method with a charged aerosol detector (RPLC-CAD). The hydrogel studied consists of modified hydroxypropylmethylcellulose, self-assembled PEG-b-PLA nanoparticles, and a therapeutic compound, bimatoprost. The three components were resolved and quantitated using the RPLC-CAD method with a C4 stationary phase. The method demonstrated robust performance, applicability to alternative cargos (i.e., proteins) and was suitable for composition analysis as well as for evaluating in vitro release of cargos from the hydrogel. Moreover, this method can be used to monitor polymer degradation and material stability, which can be further elucidated by coupling the RPLC method with (1) a multi-angle light scattering detector (RPLC-MALS) or (2) high resolution mass spectrometry (RPLC-MS) and a Fourier-transform based deconvolution algorithm. We envision that this analytical strategy could be generalized to characterize critical quality attributes of other classes of supramolecular hydrogels, establish structure-property relationships, and provide rational design guidance in hydrogel drug product development.

  View details for DOI 10.1021/acs.analchem.3c05747

  View details for PubMedID 38567987

• A Regimen Compression Strategy for Commercial Vaccines Leveraging an Injectable Hydrogel Depot Technology for Sustained Vaccine Exposure ADVANCED THERAPEUTICS Yan, J., Ou, B. S. S., Saouaf, O. M. M., Meany, E. L. L., Eckman, N., Appel, E. A. A. 2023

  View details for DOI 10.1002/adtp.202300108

  View details for Web of Science ID 001004577500001

• A freely suspended robotic swimmer propelled by viscoelastic normal stresses JOURNAL OF FLUID MECHANICS Kroo, L. A., Binagia, J. P., Eckman, N., Prakash, M., Shaqfeh, E. S. G. 2022; 944

  View details for DOI 10.1017/jfm.2022.485

  View details for Web of Science ID 000817205500001

• In Situ Direct Laser Writing of 3D Graphene-Laden Microstructures ADVANCED MATERIALS TECHNOLOGIES Restaino, M., Eckman, N., Alsharhan, A. T., Lamont, A. C., Anderson, J., Weinstein, D., Hall, A., Sochol, R. D. 2021; 6 (8)

  View details for DOI 10.1002/admt.202100222

  View details for Web of Science ID 000663380000001

• Ignition and combustion analysis of direct write fabricated aluminum/metal oxide/PVDF films COMBUSTION AND FLAME Rehwoldt, M. C., Wang, H., Kline, D. J., Wu, T., Eckman, N., Wang, P., Agrawal, N. R., Zachariah, M. R. 2020; 211: 260-269

  View details for DOI 10.1016/j.combustflame.2019.08.023

  View details for Web of Science ID 000503319100022

• Why does adding a poor thermal conductor increase propagation rate in solid propellants? APPLIED PHYSICS LETTERS Kline, D. J., Rehwoldt, M. C., Wang, H., Eckman, N. E., Zachariah, M. R. 2019; 115 (11)

  View details for DOI 10.1063/1.5113612

  View details for Web of Science ID 000486002700007

• Direct Writing of a 90 wt% Particle Loading Nanothermite ADVANCED MATERIALS Wang, H., Shen, J., Kline, D. J., Eckman, N., Agrawal, N. R., Wu, T., Wang, P., Zachariah, M. R. 2019; 31 (23): e1806575

  Abstract

  The additive manufacturing of energetic materials has received worldwide attention. Here, an ink formulation is developed with only 10 wt% of polymers, which can bind a 90 wt% nanothermite using a simple direct-writing approach. The key additive in the ink is a hybrid polymer of poly(vinylidene fluoride) (PVDF) and hydroxy propyl methyl cellulose (HPMC) in which the former serves as an energetic initiator and a binder, and the latter is a thickening agent and the other binder, which can form a gel. The rheological shear-thinning properties of the ink are critical to making the formulation at such high loadings printable. The Young's modulus of the printed stick is found to compare favorably with that of poly(tetrafluoroethylene) (PTFE), with a particle packing density at the theoretical maximum. The linear burn rate, mass burn rate, flame temperature, and heat flux are found to be easily adjusted by varying the fuel/oxidizer ratio. The average flame temperatures are as high as ≈2800 K with near-complete combustion being evident upon examination of the postcombustion products.

  View details for DOI 10.1002/adma.201806575

  View details for Web of Science ID 000474087100019

  View details for PubMedID 30993751