Carolyn Jons

All Publications

• Polyacrylamide-Based Antimicrobial Copolymers to Replace or Rescue Antibiotics. ACS central science Williams, S. C., Chosy, M. B., Jons, C. K., Dong, C., Prossnitz, A. N., Liu, X., Hernandez, H. L., Cegelski, L., Appel, E. A. 2025; 11 (3): 486-496

  Abstract

  Antibiotics save countless lives each year and have dramatically improved human health outcomes since their introduction in the 20th century. Unfortunately, bacteria are now developing resistance to antibiotics at an alarming rate, with many new strains of "superbugs" showing simultaneous resistance to multiple classes of antibiotics. To mitigate the global burden of antimicrobial resistance, we must develop new antibiotics that are broadly effective, safe, and highly stable to enable global access. In this manuscript, we report the development of polyacrylamide-based copolymers as a class of broad-spectrum antibiotics with efficacy against several critical pathogens. We demonstrate that these copolymer drugs are selective for bacteria over mammalian cells, indicating a favorable safety profile. We show that they kill bacteria through a membrane disruption mechanism, which allows them to overcome traditional mechanisms of antimicrobial resistance. Finally, we demonstrate their ability to rehabilitate an existing small-molecule antibiotic that is highly subject to resistance development by improving its potency and eliminating the development of resistance in a combination treatment. This work represents a significant step toward combating antimicrobial resistance.

  View details for DOI 10.1021/acscentsci.4c01973

  View details for PubMedID 40161953

  View details for PubMedCentralID PMC11950845

• Sustained Vaccine Exposure Elicits More Rapid, Consistent, and Broad Humoral Immune Responses to Multivalent Influenza Vaccines. Advanced science (Weinheim, Baden-Wurttemberg, Germany) Saouaf, O. M., Ou, B. S., Song, Y. E., Carter, J. J., Yan, J., Jons, C. K., Barnes, C. O., Appel, E. A. 2025: e2404498

  Abstract

  With the ever-present threat of pandemics, it is imperative vaccine technologies eliciting broad and durable immunity to high-risk pathogens are developed. Yet, current annual influenza vaccines, for example, fail to provide robust immunity against the 3-4 homologous strains they contain, let alone heterologous strains. Herein, this study demonstrates that sustained delivery of multivalent influenza vaccines from an injectable polymer-nanoparticle (PNP) hydrogel technology induces more rapid, consistent, and potent humoral immune responses against multiple homologous viruses, as well as potent responses against heterologous viruses and potential pandemic subtypes H5N1, H7N9 and H9N2. Further, admixing PNP hydrogels with commercial influenza vaccines results in stronger hemagglutination inhibition against both heterologous and homologous viruses. Additional investigation shows this enhanced potency and breadth arise from higher affinity antibodies targeting both the hemagglutinin stem and head. Overall, this simple and effective sustained delivery platform for multivalent annual influenza vaccines generates durable, potent, and remarkably broad immunity to influenza.

  View details for DOI 10.1002/advs.202404498

  View details for PubMedID 40091614

• Polyacrylamide-Based Antimicrobial Copolymers to Replace or Rescue Antibiotics ACS CENTRAL SCIENCE Williams, S. C., Chosy, M. B., Jons, C. K., Dong, C., Prossnitz, A. N., Liu, X., Hernandez, H., Cegelski, L., Appel, E. A. 2025

  View details for DOI 10.1021/acscentsci.4c01973

  View details for Web of Science ID 001444303300001

• 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

• 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

• Viral Vector Eluting Lenses for Single-Step Targeted Expression of Genetically-Encoded Activity Sensors for in Vivo Microendoscopic Calcium Imaging. Macromolecular bioscience Jons, C. K., Cheng, D., Dong, C., Meany, E. L., Nassi, J. J., Appel, E. A. 2024: e2400359

  Abstract

  Optical methods for studying the brain offer powerful approaches for understanding how neural activity underlies complex behavior. These methods typically rely on genetically encoded sensors and actuators to monitor and control neural activity. For microendoscopic calcium imaging, injection of a virus followed by implantation of a lens probe is required to express a calcium sensor and enable optical access to the target brain region. This two-step process poses several challenges, chief among them being the risks associated with mistargeting and/or misalignment between virus expression zone, lens probe and target brain region. Here, an adeno-associated virus (AAV)-eluting polymer coating is engineered for gradient refractive index (GRIN) lenses enabling the expression of a genetically encoded calcium indicator (GCaMP) directly within the brain region of interest upon implantation of the lens. This approach requires only one surgical step and guarantees alignment between GCaMP expression and lens in the brain. Additionally, the slow virus release from these coatings increases the working time for surgical implantation, expanding the brain regions and species amenable to this approach. These enhanced capabilities should accelerate neuroscience research utilizing optical methods and advance the understanding of the neural circuit mechanisms underlying brain function and behavior in health and disease.

  View details for DOI 10.1002/mabi.202400359

  View details for PubMedID 39283817

• Saponin nanoparticle adjuvants incorporating Toll-like receptor agonists drive distinct immune signatures and potent vaccine responses. Science advances Ou, B. S., Baillet, J., Filsinger Interrante, M. V., Adamska, J. Z., Zhou, X., Saouaf, O. M., Yan, J., Klich, J. H., Jons, C. K., Meany, E. L., Valdez, A. S., Carter, L., Pulendran, B., King, N. P., Appel, E. A. 2024; 10 (32): eadn7187

  Abstract

  Over the past few decades, the development of potent and safe immune-activating adjuvant technologies has become the heart of intensive research in the constant fight against highly mutative and immune evasive viruses such as influenza, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and human immunodeficiency virus (HIV). Herein, we developed a highly modular saponin-based nanoparticle platform incorporating Toll-like receptor agonists (TLRas) including TLR1/2a, TLR4a, and TLR7/8a adjuvants and their mixtures. These various TLRa-saponin nanoparticle adjuvant constructs induce unique acute cytokine and immune-signaling profiles, leading to specific T helper responses that could be of interest depending on the target disease for prevention. In a murine vaccine study, the adjuvants greatly improved the potency, durability, breadth, and neutralization of both COVID-19 and HIV vaccine candidates, suggesting the potential broad application of these adjuvant constructs to a range of different antigens. Overall, this work demonstrates a modular TLRa-SNP adjuvant platform that could improve the design of vaccines and affect modern vaccine development.

  View details for DOI 10.1126/sciadv.adn7187

  View details for PubMedID 39110802

  View details for PubMedCentralID PMC11305391

• Use of a biomimetic hydrogel depot technology for sustained delivery of GLP-1 receptor agonists reduces burden of diabetes management. Cell reports. Medicine d'Aquino, A. I., Maikawa, C. L., Nguyen, L. T., Lu, K., Hall, I. A., Jons, C. K., Kasse, C. M., Yan, J., Prossnitz, A. N., Chang, E., Baker, S. W., Hovgaard, L., Steensgaard, D. B., Andersen, H. B., Simonsen, L., Appel, E. A. 2023; 4 (11): 101292

  Abstract

  Glucagon-like peptide-1 (GLP-1) is an incretin hormone and neurotransmitter secreted from intestinal L cells in response to nutrients to stimulate insulin and block glucagon secretion in a glucose-dependent manner. Long-acting GLP-1 receptor agonists (GLP-1 RAs) have become central to treating type 2 diabetes (T2D); however, these therapies are burdensome, as they must be taken daily or weekly. Technological innovations that enable less frequent administrations would reduce patient burden and increase patient compliance. Herein, we leverage an injectable hydrogel depot technology to develop a GLP-1 RA drug product capable of months-long GLP-1 RA delivery. Using a rat model of T2D, we confirm that one injection of hydrogel-based therapy sustains exposure of GLP-1 RA over 42 days, corresponding to a once-every-4-months therapy in humans. Hydrogel therapy maintains management of blood glucose and weight comparable to daily injections of a leading GLP-1 RA drug. This long-acting GLP-1 RA treatment is a promising therapy for more effective T2D management.

  View details for DOI 10.1016/j.xcrm.2023.101292

  View details for PubMedID 37992687

• Subcutaneous delivery of an antibody against SARS-CoV-2 from a supramolecular hydrogel depot. Biomaterials science Kasse, C. M., Yu, A. C., Powell, A. E., Roth, G. A., Liong, C. S., Jons, C. K., Buahin, A., Maikawa, C. L., Zhou, X., Youssef, S., Glanville, J. E., Appel, E. A. 2023

  Abstract

  Prolonged maintenance of therapeutically-relevant levels of broadly neutralizing antibodies (bnAbs) is necessary to enable passive immunization against infectious disease. Unfortunately, protection only lasts for as long as these bnAbs remain present at a sufficiently high concentration in the body. Poor pharmacokinetics and burdensome administration are two challenges that need to be addressed in order to make pre- and post-exposure prophylaxis with bnAbs feasible and effective. In this work, we develop a supramolecular hydrogel as an injectable, subcutaneous depot to encapsulate and deliver antibody drug cargo. This polymer-nanoparticle (PNP) hydrogel exhibits shear-thinning and self-healing properties that are required for an injectable drug delivery vehicle. In vitro drug release assays and diffusion measurements indicate that the PNP hydrogels prevent burst release and slow the release of encapsulated antibodies. Delivery of bnAbs against SARS-CoV-2 from PNP hydrogels is compared to standard routes of administration in a preclinical mouse model. We develop a multi-compartment model to understand the ability of these subcutaneous depot materials to modulate the pharmacokinetics of released antibodies; the model is extrapolated to explore the requirements needed for novel materials to successfully deliver relevant antibody therapeutics with different pharmacokinetic characteristics.

  View details for DOI 10.1039/d2bm00819j

  View details for PubMedID 36723072

• Yield-Stress and Creep Control Depot Formation and Persistence of Injectable Hydrogels Following Subcutaneous Administration ADVANCED FUNCTIONAL MATERIALS Jons, C. K., Grosskopf, A. K., Baillet, J., Yan, J., Klich, J. H., Saouaf, O. M., Appel, E. A. 2022

  View details for DOI 10.1002/adfm.202203402

  View details for Web of Science ID 000835848500001

• Delivery of CAR-T cells in a transient injectable stimulatory hydrogel niche improves treatment of solid tumors. Science advances Grosskopf, A. K., Labanieh, L., Klysz, D. D., Roth, G. A., Xu, P., Adebowale, O., Gale, E. C., Jons, C. K., Klich, J. H., Yan, J., Maikawa, C. L., Correa, S., Ou, B. S., d'Aquino, A. I., Cochran, J. R., Chaudhuri, O., Mackall, C. L., Appel, E. A. 2022; 8 (14): eabn8264

  Abstract

  Adoptive cell therapy (ACT) has proven to be highly effective in treating blood cancers, but traditional approaches to ACT are poorly effective in treating solid tumors observed clinically. Novel delivery methods for therapeutic cells have shown promise for treatment of solid tumors when compared with standard intravenous administration methods, but the few reported approaches leverage biomaterials that are complex to manufacture and have primarily demonstrated applicability following tumor resection or in immune-privileged tissues. Here, we engineer simple-to-implement injectable hydrogels for the controlled co-delivery of CAR-T cells and stimulatory cytokines that improve treatment of solid tumors. The unique architecture of this material simultaneously inhibits passive diffusion of entrapped cytokines and permits active motility of entrapped cells to enable long-term retention, viability, and activation of CAR-T cells. The generation of a transient inflammatory niche following administration affords sustained exposure of CAR-T cells, induces a tumor-reactive CAR-T phenotype, and improves efficacy of treatment.

  View details for DOI 10.1126/sciadv.abn8264

  View details for PubMedID 35394838