A cGAMP-containing hydrogel for prolonged SARS-CoV-2 RBD subunit vaccine exposure induces a broad and potent humoral response

The SARS-CoV-2 virus spike protein, specifically its receptor binding domain (RBD), has emerged as a promising target for generation of neutralizing antibodies. Although the RBD peptide subunit is easily manufactured and highly stable, RBD-based subunit vaccines have been hampered by its poor inherent immunogenicity. We hypothesize that this limitation can be overcome by sustained co-administration alongside a potent and optimized adjuvant. The innate immune second messenger, cGAMP, holds promise as it activates the potent anti-viral STING pathway, but has exhibited poor performance as a therapeutic due to its nonspecific pharmacodynamic profiles when administered systemically and its poor pharmacokinetics arising from rapid excretion and degradation by its hydrolase ENPP1. To overcome these limitations, we sought to mimic the natural scenario of viral infections by creating an artificial immunological niche that enables slow release of cGAMP and the RBD antigen. Specifically, we co-encapsulated cGAMP and RBD in an injectable polymer-nanoparticle (PNP) hydrogel system. This cGAMP-adjuvanted hydrogel vaccine elicited more potent, durable, and broad antibody responses and improved neutralization than both dose-matched bolus controls and a hydrogel-based vaccine lacking cGAMP. The cGAMP-adjuvanted hydrogel platform developed is suitable for delivery of other antigens and may provide enhanced immunity against a broad range of pathogens.

Cancer theranostic platforms based on injectable polymer hydrogels

The design of injectable polymer hydrogels for cancer theranostics is described, particularly focusing on the elements/components of theranostic hydrogels, and their cross–linking strategies, structures, and performance on drug delivery/tracking.

Advances in the Study of Lens Refilling

The ultimate goal of cataract surgery is to restore the accommodation while restoring distance visual acuity. Different kinds of accommodative intraocular lens (IOLs) and surgical techniques have been suggested to apply during the surgery, but they showed poor postoperative accommodation. It is possible to achieve this goal by refilling the lens with an injectable polymer. We present a summary of the existing materials, methods, results, and some obstacles in clinical application that remain of lens refilling for restoration of accommodation. Two main problems have restricted the clinical application of this technique. One was the formation of postoperative secondary capsule opacification and the other was the different accommodative power after surgery.

Self-Healing Injectable Polymer Hydrogel via Dynamic Thiol-Alkynone Double Addition Crosslinks

<p>Introduction of dynamic thiol-alkynone double addition crosslinks in a polymer network enable the formation of a self-healing injectable polymer hydrogel. A 4-arm polyethylene glycol (PEG) tetra-thiol star polymer is crosslinked by a small molecule alkynone via the thiol-alkynone double adduct, to generate a hydrogel network under ambient aqueous conditions (buffer pH=7.4 or 8.2, room temperature). The mechanical properties of these hydrogels can be easily tuned by varying the concentration of polymer precursors. Through the dynamic thiol-alkynone double addition crosslink, these hydrogels are self-healing and shear thinning, as demonstrated by rheological measurements, macroscopic self-healing and injection tests. These hydrogels can be injected through a 20G syringe needle and recover after extrusion. In addition, good cytocompatibility of these hydrogels is confirmed by cytotoxicity test. This work shows the application of a new type of dynamic covalent chemistry in the straightforward preparation of self-healing injectable hydrogels, which may find future biomedical applications such as tissue engineering and drug delivery.</p>