Biology subjects

Ung, T.

Publications and source records attributed to Ung, T..

2 recordsLinked to original sources

bioRxiv2024

A Mechanically Resilient Soft Hydrogel Improves Drug Delivery for Treating Post-Traumatic Osteoarthritis in Physically Active Joints

Intra-articular delivery of disease-modifying osteoarthritis drugs (DMOADs) is likely to be most effective in early post-traumatic osteoarthritis (PTOA) when symptoms are minimal and patients are physically active. DMOAD delivery systems therefore must withstand repeated mechanical loading without affecting the drug release kinetics. Although soft materials are preferred for DMOAD delivery, mechanical loading can compromise their structural integrity and disrupt drug release. Here, we report a mechanically resilient soft hydrogel that rapidly self-heals under conditions resembling human running while maintaining sustained release of the cathepsin-K inhibitor L-006235 used as a proof-of-concept DMOAD. Notably, this hydrogel outperformed a previously reported hydrogel designed for intra-articular drug delivery, used as a control in our study, which neither recovered nor maintained drug release under mechanical loading. Upon injection into mouse knee joints, the hydrogel showed consistent release kinetics of the encapsulated agent in both treadmill-running and non-running mice. In a mouse model of aggressive PTOA exacerbated by treadmill running, L-006235 hydrogel markedly reduced cartilage degeneration. To our knowledge, this is the first hydrogel proven to withstand human running conditions and enable sustained DMOAD delivery in physically active joints, and the first study demonstrating reduced disease progression in a severe PTOA model under rigorous physical activity, highlighting the hydrogels potential for PTOA treatment in active patients.

bioengineering↗

bioRxiv2024

β-glucan induced trained immunity enhances antibody levels in a vaccination model in mice

Trained immunity improves disease resistance by strengthening our first line of defense, the innate immune system. Innate immune cells, predominantly macrophages, are epigenetically and metabolically rewired by {beta}-glucan, a fungal cell wall component, to induce trained immunity. These trained macrophages exhibit increased co-stimulatory marker expression and altered cytokine production. Signaling changes from antigen-presenting cells, including macrophages, polarize T-cell responses. Recent work has shown that trained immunity can generally enhance protection against infection, and some work has shown increased protection with specific vaccines. It has been hypothesized that the trained cells themselves potentially modulate adaptive immunity in the context of vaccines. However, the mechanistic link between trained immunity on subsequent vaccinations to enhance antibody levels has not yet been identified. We report that trained immunity induced by a single dose of {beta}-glucan increased antigen presentation in bone-marrow-derived macrophages (BMDMs) and CD4+ T cell proliferation in-vitro. Mice trained with a single dose of {beta}-glucan a week before vaccination elicited higher antigen-specific antibody levels than untrained mice. Further experiments validate that macrophages mediate this increase. This effect persisted even after vaccinations with 100 times less antigen in trained mice. We report {beta}-glucan training as a novel prophylactic method to enhance the effect of subsequent vaccines.

immunology↗