Dynamic covalent networks (DCvNs) are increasingly used in advanced materials design with applications ranging from recyclable thermosets to self-healing hydrogels. However, the relationship between the underlying chemistry at the junctions of DCvNs and their macroscopic properties is still not fully understood. In this work, we constructed a robust framework to predict how complex network behavior in DCvNs emerges from the chemical landscape of the dynamic chemistry at the junction. Ideal dynamic covalent boronic ester-based hydrogels were used as model DCvNs. We developed physical models that describe how viscoelastic properties, as measured by shear rheometry, are linked to the molecular behavior of the dynamic junction, quantified via fluorescence and NMR spectroscopy and DFT calculations. Additionally, shear rheometry was combined with Transition State Theory to quantify the kinetics and thermodynamics of network rearrangements, enabling a mechanistic understanding including preferred reaction pathways for dynamic covalent chemistries. We applied this approach to corroborate the "loose-bolt" postulate for the reaction mechanism in Wulff-type boronic acids. These findings, grounded in molecular principles, advance our understanding and rational design of dynamic polymer networks, improving our ability to predict, design, and leverage their unique properties for future applications.

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Hydrogel adhesion inherently relies on engineering the contact surface at soft and hydrated interfaces. Upon contact, adhesion normally occurs through the formation of chemical or physical interactions between the disparate surfaces. The ability to form these adhesion junctions is challenging for hydrogels as the interfaces are wet and deformable and often contain low densities of functional groups. In this Review, we link the design of the binding chemistries or adhesion junctions, whether covalent, dynamic covalent, supramolecular, or physical, to the emergent adhesive properties of soft and hydrated interfaces. Wet adhesion is useful for bonding to or between tissues and implants for a range of biomedical applications. We highlight several recent and emerging adhesive hydrogels for use in biomedicine in the context of efficient junction design. The main focus is on engineering hydrogel adhesion through molecular design of the junctions to tailor the adhesion strength, reversibility, stability, and response to environmental stimuli.

Moldable hydrogels composed of dynamic covalent bonds are attractive biomaterials for controlled release, as the dynamic exchange of bonds in these networks enables minimally invasive application via injection. Despite the growing interest in the biomedical application of dynamic covalent hydrogels, there is a lack of fundamental understanding as to how the network design and local environment control the release of biomolecules from these materials. In this work, we fabricated boronicester-based dynamic covalent hydrogels for the encapsulation and in vitro release of a model biologic (β-galactosidase). We systematically investigated the role of network properties and of the external environment (temperature and presence of competitive binders) on release from these dynamic covalent hydrogels. We observed that surface erosion (and associated mass loss) governed biomolecule release. In addition, we developed a statistical model of surface erosion based on the binding equilibria in a boundary layer that described the rates of release. In total, our results will guide the design of dynamic covalent hydrogels as biomaterials for drug delivery applications.

Antimicrobial resistance (AMR) develops when bacteria no longer respond to conventional antimicrobial treatment. The limited treatment options for resistant infections result in a significantly increased medical burden. Antimicrobial peptides offer advantages for treatment of resistant infections, including broad-spectrum activity and lower risk of resistance development. However, sensitivity to proteolytic cleavage often limits their clinical application. Here, a moldable and biodegradable colloidal nano-network is presented that protects bioactive peptides from enzymatic degradation and delivers them locally. An antimicrobial peptide, PA-13, is encapsulated electrostatically into positively and negatively charged nanoparticles made of chitosan and dextran sulfate without requiring chemical modification. Mixing and concentration of oppositely charged particles form a nano-network with the rheological properties of a cream or injectable hydrogel. After exposure to proteolytic enzymes, the formed nano-network loaded with PA-13 eliminates Pseudomonas aeruginosa during in vitro culture and in an ex vivo porcine skin model while the unencapsulated PA-13 shows no antibacterial effect. This demonstrates the ability of the nano-network to protect the antimicrobial peptide in an enzyme-challenged environment, such as a wound bed. Overall, the nano-network presents a useful platform for antimicrobial peptide protection and delivery without impacting peptide bioactivity.