Biology subjects

Song, Y. E.

Publications and source records attributed to Song, Y. E..

10 recordsLinked to original sources

bioRxiv2026

Sustained Delivery of a SARS-CoV-2 Subunit Vaccine in An Adjuvanted Hydrogel Depot Enhances Vaccine Responses in Nonhuman Primates

While natural infections expose the immune system for days to weeks of inflammation and antigen presentation, immunizations with conventional bolus vaccines often lead to rapid clearance of antigens and adjuvants. Prolonged exposure to vaccines using controlled delivery devices or repeated dosing regimens has been shown to enhance germinal center reactions, leading to improved humoral responses, including increased magnitude of antibody titers and enhanced neutralizing activity. Herein, we report the use of injectable polymer-nanoparticle (PNP) hydrogels as a vaccine depot technology for sustained delivery of the clinically relevant SARS-CoV-2 Hexapro subunit antigen and a toll-like receptor agonist adjuvant. In mice, we demonstrated that PNP hydrogel vaccines enhanced germinal center responses and antibody responses relative to bolus vaccination. In nonhuman primates, hydrogel vaccines induced enhanced and durable antibody responses against wildtype and variants of concern such as Omicron BA.5 compared to bolus vaccination. We report the first use of a biomaterials-based approach for sustained delivery of vaccines in nonhuman primates, further advancing toward clinical translation.

bioengineering↗

bioRxiv2026

Structure-Property-Performance Engineering of Hydrogel Depots for Long-Acting Peptide Delivery

Controlled release systems for subcutaneous peptide delivery often exhibit a pronounced initial burst release followed by inadequate maintenance of therapeutic exposure, limiting depot lifetime and increasing pharmacokinetic variability. Here, we engineer a dynamic, injectable hydrogel depot technology for months-long delivery of lipidated peptides. Using semaglutide as a model, we establish a modular formulation framework integrating: (i) formulation-driven tuning of depot mechanics to control release kinetics, (ii) cargo complexation strategies leveraging hydrophobic and multivalent ion-mediated interactions, and (iii) oxidative stabilization through sacrificial antioxidant excipients. We evaluated depot performance by rheology, in vitro cargo release, and in vivo pharmacokinetic and pharmacodynamic studies in rodents. Optimized formulations sustained semaglutide exposure for over six weeks from a single administration with two-fold reduction in peak-to-trough exposure and comparable total bioavailability relative to daily dosing, resulting in improved glucose control, weight regulation, and preservation of pancreatic islet content. These results suggest potential for quarterly dosing in humans. Together, this work establishes integrated and generalizable structure-property-performance relationships that account for cargo-matrix and cargo-excipient interactions across burst, diffusion, and erosion regimes to inform a practical formulation framework for engineering long-acting depots for sustained peptide delivery.

bioengineering↗

bioRxiv2026

Sustained Delivery of a Shingles Subunit Vaccine Overcomes Age-Related Declines in Humoral and Cellular Immunity Relative to Shingrix

The global aging population faces heightened vulnerability to infectious diseases due to immunosenescence, which diminishes the potency, durability, and breadth of vaccine-induced immunity. While the leading shingles vaccine, Shingrix(R), provides protection against herpes zoster virus for adults aged 50 and older, it is often associated with severe local and systemic reactogenicity, which limits vaccine compliance. Here, we report an injectable polymer-nanoparticle (PNP) hydrogel platform for the sustained delivery of a shingles subunit vaccine to enhance immune responses while mitigating reactogenicity in aged mice. Hydrogel-based vaccination elicited significantly more potent and durable humoral immune responses than Shingrix(R), while inflammatory cytokine levels remained below the limit of detection. Moreover, aged mice vaccinated with the hydrogel-based vaccine exhibited robust antigen-specific cellular immune responses. These findings demonstrate that controlling the temporal presentation of vaccine components can overcome age-associated declines in immune responsiveness without inducing excessive inflammatory signaling. By decoupling immunogenicity from reactogenicity, our hydrogel-based delivery strategy offers a promising approach to improve both the efficacy and tolerability of subunit vaccines for the elderly and may be broadly applicable to other vaccines targeting aging populations.

immunology↗

bioRxiv2025

Long-acting hydrogel-based depot formulations of tirzepatide and semaglutide for the management of type 2 diabetes and weight

Several incretin hormone therapies have been clinically approved and have revolutionized the treatment of diabetes and obesity. Promising therapeutics include semaglutide (Ozempic(R) and Wegovy(R)), an agonist for glucagon-like peptide-1 (GLP-1) receptor, and tirzepatide (Mounjaro(R)), a dual agonist for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors. These molecules help to regulate blood glucose levels, enhance insulin secretion and sensitivity, and reduce appetite. Currently, these treatments require weekly injections, which can be challenging for patients to adhere to. We recently reported the development of an injectable hydrogel depot technology enabling months-long release of semaglutide (Sema). Here, we further develop this technology for improved prolonged release of both Sema and tirzepatide (TZP). In a rat model of diabetes, we show a single administration of hydrogel-based formulations of either Sema or TZP maintained relevant drug levels for over 6 weeks. In these studies, single administrations of long-acting hydrogel-based therapies of Sema or TZP were similarly effective at regulating blood glucose and weight compared to daily injections of either Sema or TZP in standard aqueous vehicles. This hydrogel depot technology is easy to manufacture, injectable, and exhibits excellent biocompatibility, enabling months-long-acting treatments with the potential to improve management of diabetes and weight.

bioengineering↗

bioRxiv2025

Engineering Sustained-Release Broadly Neutralizing Antibody Formulations

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. In-vivo studies in mice and rats demonstrate prolonged protein release, 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.

bioengineering↗

bioRxiv2025

Preventing peritendinous adhesions using lubricious supramolecular hydrogels

Of the 1.5 million emergency room visits each year in the United States due to flexor tendon injuries in the hand, over 30-40% result in peritendinous adhesions which can limit range of motion (ROM) and severely impact an individuals quality of life. Adhesions are fibrous scar-like tissues which can form between adjacent tissues in the body in response to injury, inflammation, or during normal healing following surgery. Currently, there is no widespread solution for adhesion prevention in the delicate space of the digit while allowing a patient full ROM quickly after surgery. There is a clear clinical need for a material capable of limiting adhesion formation which is simple to apply, does not impair healing, remains at the application site during motion and initial inflammation (days - weeks), and leaves tendon glide unencumbered. In this work, we developed dynamically crosslinked, bioresorbable supramolecular hydrogels as easy-to-apply lubricious barriers to prevent the formation of peritendinous adhesions. These hydrogels exhibit excellent long-term stability, injectability, and thermally stable viscoelastic properties that allow for simple storage and facile application. We evaluated interactions at the interface of the hydrogels and relevant tissues, including human tendon and skin, in shear and extensional stress modes and demonstrated a unique mechanism of adhesion prevention based on maintenance of a lubricious hydrogel barrier between tissues. Ex vivo studies show that the hydrogels did not impair the gliding behavior nor mechanical properties of tendons when applied in cadaveric human hands following clinically relevant flexor tendon repair. We further applied these hydrogels in a preclinical rat Achilles tendon injury model and observed prolonged local retention at the repair site as well as improved recovery of key functional metrics, including ROM and maximal dorsiflexion. Further, these hydrogels were safe and did not impair tendon strength nor healing compared to the current standard of care. These dynamic, biocompatible hydrogels present a novel solution to the significant problem of peritendinous adhesions with clear translational potential.

bioengineering↗

bioRxiv2024

Highly extensible physically crosslinked hydrogels for high-speed 3D bioprinting

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, we report a highly extensible bioink system created by modulating the rheology of physically crosslinked hydrogels comprising hydrophobically-modified cellulosics and either surfactants or cyclodextrins. We demonstrate 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. We demonstrate the potential of these hydrogels for use as bioinks by evaluating the relationship between extensibility and printability, demonstrating that greater hydrogel extensibility enables faster print speeds and smaller print features. Our 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.

bioengineering↗

bioRxiv2024

Generation of an inflammatory niche in an injectable hydrogel depot through recruitment of key immune cells improves efficacy of mRNA vaccines

Messenger RNA (mRNA) delivered in lipid nanoparticles (LNPs) rose to the forefront of vaccine candidates during the COVID-19 pandemic due in part 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 depot 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 SARS-CoV-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.

bioengineering↗

bioRxiv2024

Star-polymers as potent broad-spectrum extracellular virucidal antivirals

Viruses pose a significant threat to both global health and the global economy. It is clear that novel antiviral strategies are urgently needed, with a broad-spectrum approach being most desired. We have discovered a broad-spectrum, non-toxic polymer virucide that can tackle the viral threat. This polymeric virucide is effective at nanomolar concentrations, against a broad-spectrum of viruses and, demonstrated using an intranasal respiratory syncytial virus (RSV) murine model, has excellent efficacy, low anti-coagulant properties and low toxicity in vivo. Molecular dynamic simulations show that this polymer achieves its virucidal antiviral effect via self-assembly of viral-receptors leading to increased envelope forces and viral disassembly. The discovery of this cheap and readily produced polymer marks the start of a new type of receptor-crosslinking broad-spectrum antiviral that has significant potential to combat the global threat posed by viruses.

microbiology↗

bioRxiv2024

Sustained vaccine exposure elicits more rapid, consistent, and broad humoral immune responses to multivalent influenza vaccines

With the ever-present threat of pandemics, it is imperative we develop vaccine technologies eliciting broad and durable immunity to high-risk pathogens. 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, we demonstrate 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. We show this enhanced potency and breadth arises 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.

bioengineering↗